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Review

Pillararene-Based Supramolecular Polymers for Cancer Therapy

by
Miaomiao Yan
and
Jiong Zhou
*
Department of Chemistry, College of Sciences, Northeastern University, Shenyang 110819, China
*
Author to whom correspondence should be addressed.
Molecules 2023, 28(3), 1470; https://doi.org/10.3390/molecules28031470
Submission received: 3 January 2023 / Revised: 30 January 2023 / Accepted: 31 January 2023 / Published: 3 February 2023
(This article belongs to the Special Issue Supramolecular Cancer Nanotheranostics)
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Abstract

:
Supramolecular polymers have attracted considerable interest due to their intriguing features and functions. The dynamic reversibility of noncovalent interactions endows supramolecular polymers with tunable physicochemical properties, self-healing, and externally stimulated responses. Among them, pillararene-based supramolecular polymers show great potential for biomedical applications due to their fascinating host–guest interactions and easy modification. Herein, we summarize the state of the art of pillararene-based supramolecular polymers for cancer therapy and illustrate its developmental trend and future perspective.

1. Introduction

Cancer has become one of the “biggest killers” of human beings worldwide [1,2,3,4,5]. Cancer poses a threat to human health, claiming millions of lives each year [6,7,8,9,10]. Up to date, due to the malignant proliferation and complexity of tumors, existing cancer therapies generally destroy cancer cells, accompanied by some side effects [11,12]. Radiotherapy, chemotherapy, and surgical excision are generally considered the main treatments for cancer [13,14]. However, radiotherapy is a kind of local therapy that will produce a certain radiation reaction, which often brings certain toxic side effects and irreversible local damage [15]. In contrast, surgical resection may be a more direct approach to treat cancer. However, it causes huge distress to cancer patients and risks tumor cell migration [16]. As a systemic treatment, chemotherapy can kill local or distant metastatic tumors, but serious side effects on the body are inevitable [17,18]. Due to the limitations and side effects of these three traditional therapies, exploring new strategies for cancer therapy is urgently needed [19,20,21,22,23,24,25].
In recent years, the application of supramolecular chemistry in the field of biomedicine has attracted wide attention [26,27,28,29,30,31,32,33,34]. Supramolecular chemistry is ”chemistry beyond the molecule” [35,36,37,38,39,40]. Among them, supramolecular polymers not only combine the merits of supramolecular chemistry and polymer materials, but also possess novel structures and functions [41,42,43,44]. Supramolecular polymers refer to the ones based on monomeric units held together by directional and reversible noncovalent interactions [45,46]. Usually, supramolecular polymers are obtained via the self-assembly of building units, such as the noncovalent polymerization of covalent monomers and noncovalent crosslinking of linear polymers [47,48]. Noncovalent interactions, such as hydrogen bonding, host–guest interactions, and metal-ligand coordination, have been exploited to drive the self-assembly of building blocks [49,50,51]. The dynamic reversibility of noncovalent interactions endows supramolecular polymers with excellent properties, such as external stimulus response, self-healing, and degradability [52,53,54,55,56]. Compared with traditional polymers, it is much easier for supramolecular polymers to adjust their chemical and physical properties by changing solvents, concentrations, temperatures, or introducing new stimuli-responsive groups [57,58].
Pillararenes are the fifth generation of macrocyclic hosts next to crown ethers, cyclodextrins, calixarenes, and cucurbiturils [59,60,61,62,63,64,65,66,67,68,69,70,71], which are connected by methylene bridges at para-positions with hydroquinone as the repeating unit (Figure 1) [72,73,74]. The electron-rich cavity and unique pillar-shaped structure of pillararenes endow them with an excellent ability to bind guests [75,76,77]. In addition, various functional groups can be easily attached to the rim of pillararenes for their facile preparation and flexible modification [78,79]. The fascinating host–guest interaction and easy modification of pillararenes make them ideal materials for the preparation of supramolecular polymers [80,81,82,83]. Pillararene-based supramolecular polymers play an important role in cancer therapy, which can effectively solve some limitations of traditional materials in clinical applications [84,85]. The structure of supramolecular polymers may be controlled by the high self-selectivity based on host–guest interactions, and the rich environmental responsiveness based on noncovalent interactions can trigger the release of anticancer drugs through various stimuli [86,87].
In this review, we summarize the research progress of pillararene-based supramolecular polymers for cancer therapy over the past few years, including linear supramolecular polymers, branched supramolecular polymers, crosslinked supramolecular polymers, and supramolecular block copolymers. Moreover, the development prospects and challenges of pillararene-based supramolecular polymers for cancer therapy are extensively discussed. It is expected that this work will provide a reference for researchers interested in fields such as pillararene or cancer therapy.

2. Pillararene-Based Linear Supramolecular Polymers for Cancer Therapy

Linear supramolecular polymers, known as main-chain supramolecular polymers, are composed of monomers with bifunctional groups linked by noncovalent bonds [88,89]. Linear supramolecular polymers are the most common supramolecular polymers, which have several types such as AA, AB, AA/BB, and ABBA types [90,91]. The dynamic and reversible noncovalent interactions of pillararene endow the supramolecular polymers with outstanding stimuli-responsive features [92]. In recent years, pillararene-based functional supramolecular polymers as stimuli-responsive materials have been widely used in the fields of biology, medicine, and materials science [93,94]. Especially, pillararene-based linear supramolecular polymers have been recognized as effective materials for cancer therapy [95,96,97,98].
Photodynamic therapy (PDT) has become a cancer therapy strategy in the spotlight due to its advantages of low side effects, high selectivity, and low drug resistance [99,100,101,102]. It uses photosensitizers (PSs) and molecular oxygen to generate cytotoxic reactive oxygen species (ROS) to kill tumor cells under the irradiation of specific wavelengths. Compared with type-II PSs that generate singlet oxygen through energy transfer, type-I PSs are more advantageous in PDT because they can reduce the dependence of tumors on O2, and eliminate tumor cells efficiently even under hypoxic conditions [103,104,105]. Yang and co-workers prepared supramolecular polymeric PSs using a classical type-II PS (iodide BODIPY) as the guest molecule and electron-rich bispillar[5]arene (BP5A) as the macrocyclic host and electron donor [106]. The host–guest interaction shortened the distance between the BODIPY and the BP5A, which promoted the electron transfer of the BP5A to the BODIPY, resulting in the generation of a superoxide radical (O2−∙) through the type-I mechanism (Figure 2I). Antitumor studies showed that these supramolecular PSs had almost no dark toxicity under normoxic and hypoxic environments. Supramolecular PSs could kill HeLa cells effectively after irradiating with light for 10 min even under a hypoxic environment (Figure 2II), and exhibited an outstanding tumor-selective fluorescence imaging effect (Figure 2III). This work utilized host–guest interactions to convert type-II PSs into type-I PSs, achieving the effective regulation of both type-I and type-II mechanisms.
Monotherapy does not meet the clinical need for the effective treatment of cancer [107,108]. Thus, the synergistic combination strategy of multiple therapeutic modalities has become one of the main means to treat tumors [109,110]. Wang, Yao, and co-workers developed a pillar[5]arene-based supramolecular therapeutic nanoplatform (SP/GOx NPs) for synergistic chemo–chemodynamic therapy (Figure 3I) [111]. SP/GOx NPs could be easily loaded with DOX and modified target molecules (FA-Py) on their surfaces due to excellent host–guest properties. As the generated FA-Py/SP/GOx/Dox NPs entered the blood circulation, FA-Py could effectively target cancer cells and GOx could catalyze the overexpression of glucose in cancer cells to produce H2O2. H2O2 would form ∙OH under the catalysis of bridged ferrocene units. Thereby, the cancer cells were successfully killed and chemodynamic therapy was realized. In addition, the loaded DOX molecules were released in the acidic microenvironment to achieve synergistic chemotherapy. There was no significant change in the body weight of the mice after different treatments, showing the excellent biocompatibility and safety of pillar[5]arene-based nanomaterials (Figure 3II). Moreover, FA-Py/SP/GOx/Dox NPs showed the best antitumor effect, which illustrated the important role of the target molecule, and also demonstrated the outstanding therapeutic effect of targeted/synergistic chemo–chemodynamic therapy (Figure 3III). This study demonstrated that pillar[5]arene-based supramolecular polymers could be used as effective materials for targeted and combined chemo–chemodynamic therapy.

3. Pillararene-Based Branched Supramolecular Polymers for Cancer Therapy

In addition to the pillararene-based linear supramolecular polymers, pillararene-based branched supramolecular polymers have been employed for tumor diagnosis and therapy [112,113]. Branched supramolecular polymers have multiple branched sites, which can be constructed through noncovalent interactions or covalent synthesis [114,115]. The structure of branched supramolecular polymers can be subdivided into star, brush, hyperbranched, and other structures [116]. Pillararene-based branched supramolecular polymers with abundant terminal groups and reversible and tunable properties have potential applications in biomedicine and materials chemistry, especially in cancer therapy.
Brush polymers are a class of branched or grafted polymers, whose polymeric side-chains are usually attached to a linear backbone [117]. The distinctive topological structure and relatively low critical aggregation concentration endow brush polymers with incomparable advantages in biomedical applications [118,119]. In addition, due to the compact structure, a large number of drugs can be loaded into the self-assembly formed by brush polymers, thus providing sufficient drug concentration at the active site [120]. There are many brush polymers used in cancer therapy to improve anticancer efficacy and reduce side effects [121]. For example, Chen, Huang, and co-workers also synthesized another brush supramolecular polymer based on pillar[5]arene for targeted drug delivery (Figure 4a(I)) [122]. DOX, a widely used chemotherapeutic drug, was encapsulated into the interior of supramolecular nanoparticles constructed by a pillar[5]arene-based amphiphilic supramolecular brush copolymer. Under the action of intracellular reductase and low pH environment, the loaded DOX was released. The energy transfer relay effect between DOX and tetraphenylethene was interrupted, enabling the in situ visualization of the drug release by observing the location and magnitude of the energy transfer-dependent fluorescence changes. Additionally, supramolecular nanoparticles reduced the aggregation of nanocarriers through the formation of a “brush-like” structure, which could increase the blood circulation time. Thus, the drug was more likely to reach the target location before it was recognized and internalized by phagocytes and excreted by the reticuloendothelial system. The blood circulation time of DOX-loaded nanoparticles was much longer than that of free DOX, thus giving nanoparticles more chances to extravasate from tumor vessels (Figure 4a(II)). In vivo experiments indicated that DOX-loaded nanoparticles showed an excellent anticancer activity with negligible systemic toxicity (Figure 4b(III)).
Stimuli-responsive polymers have attracted considerable attention for their potential applications in biomedical materials [123,124,125,126]. Among various stimuli, light is a particularly attractive option due to its characteristics of convenience, cleanliness, and controllability [127,128,129]. Owing to its specific spatial and temporal controllability, photomedicine has been widely used in cancer therapy [130,131]. Tong, Jiang, and co-workers prepared a host–guest complex between pillar[6]arene and azobenzene-containing block copolymers (Figure 4b(I)) [132]. The resulting supramolecular complex was further self-assembled to form vesicles in PBS solution, where the release rate of DOX·HCl could be regulated by pH and light stimulation. Because of the good biocompatibility of vesicles, MTT assay proved that the cell viability was close to 100% at concentrations ranging from 100 to 500 μg m L−1, indicating that the nanocarriers had low cytotoxicity (Figure 4b(II)). Compared with free DOX·HCl, DOX·HCl-loaded vesicles showed lower cytotoxicity, which meant that encapsulating DOX·HCl in vesicles could reduce the toxicity of DOX·HCl (Figure 4b(III)). This pillararene-based drug delivery system with dual stimuli-responsiveness provided a new strategy for cancer therapy.
Molecules 28 01470 g004 550
Figure 4. (a) Schematic illustration of pillar[5]arene-based amphiphilic supramolecular brush polymers for targeted drug delivery (I). Blood circulation time of mice after injection of DOX·HCl and DOX-loaded nanoparticles (II). Tumor growth inhibition curves in tumor-bearing mice with different formulations (III) (* p < 0.05, ** p < 0.01). (reproduced with permission of Royal Society of Chemistry from ref. [122]). (b) Schematic illustration of dual-responsive controlled assembly and release of drugs in vesicles (I). Cytotoxicity of vesicles at different concentrations to MCF-7 cells (II). Effects of DOX·HCl-loaded vesicles and free drugs on proliferation of MCF-7 cells in vitro (III). (reproduced with permission of Elsevier from ref. [132]).
Figure 4. (a) Schematic illustration of pillar[5]arene-based amphiphilic supramolecular brush polymers for targeted drug delivery (I). Blood circulation time of mice after injection of DOX·HCl and DOX-loaded nanoparticles (II). Tumor growth inhibition curves in tumor-bearing mice with different formulations (III) (* p < 0.05, ** p < 0.01). (reproduced with permission of Royal Society of Chemistry from ref. [122]). (b) Schematic illustration of dual-responsive controlled assembly and release of drugs in vesicles (I). Cytotoxicity of vesicles at different concentrations to MCF-7 cells (II). Effects of DOX·HCl-loaded vesicles and free drugs on proliferation of MCF-7 cells in vitro (III). (reproduced with permission of Elsevier from ref. [132]).
Molecules 28 01470 g004
The abnormal proliferation of the pathogenic bacteria Fusobacterium nucleatum (F. nucleatum) around colorectal cancer is usually an important cause of chemotherapy failure and drug resistance [133]. Multifunctional cationic quaternary ammonium materials are widely used in antibacterial and anticancer fields [134,135]. Chen, Yang, Gao, and co-workers constructed a dendritic supramolecular nanoparticle based on quaternary ammonium-polyamidoamine–azobenzene (Q-P-A) and carboxylatopillar[5]arene (CP[5]A) for antibacterial and antitumor therapies, namely Q-P-A@CP[5]A (Figure 5I) [136]. The -N+CH3 group on the surface of Q-P-A was accommodated in the cavity of CP[5]A, which greatly improved the biocompatibility of Q-P-A@CP[5]A. Under a pathological situation, CP[5]A could be separated from the -N+CH3 group, allowing for effective antibacterial and anticancer therapies. Compared with other treatment groups, the Q-P-A@CP[5]A and F. nucleatum treatment group showed enhanced therapeutic effects, suggesting that -N+CH3 in Q-P-A@CP[5]A could effectively limit the growth of tumors during colorectal cancer therapy (Figure 5II). The tumor weight of the oxaliplatin and F. nucleatum treatment group was large, demonstrating the relatively poor therapeutic effect of oxaliplatin in the presence of F. nucleatum, which was because F. nucleatum could cause the chemotherapy resistance of oxaliplatin. In addition, the tumor weight and size of the Q-P-A and Q-P-A@CP[5]A and F. nucleatum treatment groups were relatively small, consistent with the tumor volume. Except for the oxaliplatin treatment group, there was little change in the body weight of the mice, indicating that Q-P-A@CP[5] had few side effects and a good biocompatibility during chemotherapy (Figure 5III). This supramolecular nanoparticle based on multifunctional cationic quaternary ammonium provided an effective treatment method to overcome chemotherapy-resistant cancers caused by bacteria.
Targeted and stimuli-responsive drug delivery systems show great promise in improving cancer therapy, which have the advantages of good water solubility, few side effects, and high therapeutic efficiency [137,138,139]. Hu, Zhu, Wang, and co-workers constructed supramolecular polymersomes based on water-soluble pillar[5]arene and cationic poly(glutamamide)s to deliver the hydrophilic anticancer drug mitoxantrone (MTZ) (Figure 6I) [140]. Such polymersomes with biotin ligands exhibited a good targeting ability and could specifically deliver MTZ to biotin receptor-positive cancer cells. Meanwhile, the loaded MTZ was released through the acidic environment-induced decomposition of polymersomes. In vitro experiments demonstrated that MTZ-loaded targeted polymersomes could effectively kill cancer cells and reduce their cytotoxicity to normal cells (Figure 6II,III). With outstanding therapeutic effects, the host–guest supramolecular delivery system with targeted ligands offered new opportunities for cancer therapy.

4. Pillararene-Based Crosslinked Supramolecular Polymers for Cancer Therapy

Crosslinked polymers usually have networks or framework structures, which can be prepared by mixing multifunctional monomers [141,142,143]. As a special class of supramolecular polymers, crosslinked supramolecular polymers combine the advantages of supramolecular polymers and crosslinked polymers [144]. Due to their excellent compatibility, mechanical properties, thermal stability, wear resistance, and creep resistance, crosslinked polymers have a wide range of practical and potential applications in adsorption and separation, catalysis, and drug delivery [145,146]. Pillararenes are recognized as the fifth generation of macrocyclic host molecules, and their rigid structure and easy functionalization endow them with unique advantages in the construction of supramolecular polymers [147]. Pillararene-based crosslinked supramolecular polymers have been increasingly investigated in the biomedical field due to their unusual architectures, fascinating properties, and interesting stimuli-responsiveness.
Template preparation is an effective “top-down” approach to obtain stable materials with the desired shape and size [148,149]. Ma and co-workers developed a crosslinked pillar[6]arene nanosponge using template preparation techniques to overcome multidrug resistance (MDR) (Figure 7I) [150]. By crosslinking pillar[6]arene and removing guest molecules, nanoparticles of uniform size could be obtained to encapsulate drugs through host–guest interactions. Because the resulting nanoparticles were made up of pillar[6]arene with unoccupied cavities, these nanoparticles were also called “nanosponges (NS)”. NS showed little cytotoxicity after incubating with HeLa cells for 48 h, indicating that NS were nontoxic to HeLa cells and NS had good biocompatibility (Figure 7II). The IC50 value of DOX@NS was 3.4 μM, which was significantly lower than that of free DOX (34.4 μM), indicating that NS could overcome the MDR of cancer cells (MCF-7/ADR) (Figure 7III). Mechanism studies demonstrated that the efficient loading and stable encapsulation of anticancer drugs based on host–guest interactions were the reasons for overcoming MDR. This work illustrated that the encapsulation of anticancer drugs utilizing host–guest interactions was a promising approach to overcome MDR.
Hydrogels are three-dimensional networks of crosslinked hydrophilic polymers. Supramolecular gels are an important subclass of supramolecular polymers [151,152,153,154,155]. Due to the dynamic nature of noncovalent interactions, supramolecular gels exhibit many unique and interesting properties compared with conventional covalent polymer gels, such as responsiveness to external stimuli, reversible shear sensitivity, and excellent self-healing capabilities [156,157,158]. Lin, Wang, and co-workers reported a smart hydrogel based on water-soluble pillar[6]arene as an anticancer drug carrier that exhibited a remarkable loading capacity for DOX·HCl [159]. When the polymer network G1c was soaked in the aqueous solution of pillar[6]arene, a significantly swollen hydrogel was obtained due to the formation of inclusion complexes between the pillar[6]arene and ferrocene groups. The resultant drug-loaded hydrogel with a dramatic swelling–shrinking transition exhibited a pH-triggered drug release property. Zhang, Huang, and co-workers constructed supramolecular polymer network gels using metal coordination interactions and host–guest interactions between four appendant pillar[5]arene and neutral divalent guest molecules for controlled drug release [160]. DOSY experiments revealed the formation of supramolecular polymer structures with a high degree of polymerization. Supramolecular gels exhibited a temperature and pH responsivenesses, which could be used for the controlled release of different cargoes.
Liu and co-workers exploited a pillar[5]arene-based single-molecule-layer polymer nanocapsule for drug delivery (Figure 8I) [161]. By modifying the surface of nanocapsules with targeting peptide ligands using the host–guest interaction, a targeted smart vehicle for efficient drug delivery was obtained. MTT experiments showed that the relative survival rate of HepG2 cells was over 75%, indicating that the targeted vehicle had low cytotoxicity and good biocompatibility (Figure 8II). In addition, the smart vehicle loaded with anticancer drugs could target and penetrate into tumor cells, effectively releasing DOX to kill tumor cells, which had a good inhibitory effect on tumor cell proliferation. Compared with free DOX and DOX-nanocapsules, the absorption rate of the RGD ligand DOX-nanocap was significantly improved, indicating the efficient targeting effect of the RGD ligand modified vehicle (Figure 8III). This novel vehicle provided a good platform for cancer therapy.

5. Pillararene-Based Supramolecular Block Copolymers for Cancer Therapy

In addition to linear supramolecular polymers, branched supramolecular polymers, and crosslinked supramolecular polymers, supramolecular block copolymers as a special class of polymers have attracted the widespread interest of researchers. Supramolecular block copolymers, composed of two or more chemically distinct polymeric blocks linked by noncovalent bonds, are key components in a variety of applications [162,163]. By combining the structural and functional advantages of supramolecular polymers and block copolymers, such as low cytotoxicity, excellent biodegradability, and sensitive environmental responsiveness, supramolecular block copolymers have been widely used in biomedical engineering and other fields [164,165]. As an emerging class of functional materials, pillararene-based supramolecular block copolymers have demonstrated significant application prospects in cancer therapy [166].
Pillararene-based supramolecular block copolymers can be used to construct stimuli-responsive drug delivery systems, which are expected to realize the targeted drug release and selective killing of cancer cells [167,168,169,170,171]. Huang and co-workers constructed a pillararene-based amphiphilic supramolecular diblock polymer for targeted drug delivery (Figure 9I) [172]. Based on the host–guest interaction of pillararenes, amphiphilic supramolecular diblock copolymers were formed from the modified pillar[5]arene and a viologen salt. Moreover, the copolymers further self-assembled into polymersomes in water. The obtained polymersomes exhibited an excellent sensitivity to redox reactions, which could be used as an effective switch to trigger the efficient release of doxorubicin hydrochloride (DOX) from the polymersomes. Compared with the group treated with the intravenous administration of free DOX and phosphate buffer solution (PBS), the DOX-loaded polymersomes were more effective in inhibiting tumor growth (Figure 9II). In vivo experiments indicated that the therapeutic effect was preserved after the encapsulating of DOX, while the damage to normal cells was reduced (Figure 9III). This work provided a new method for constructing stimuli-responsive pillararene-based supramolecular block copolymers, which had great application potential in the field of targeted drug delivery.
Xu, Cao, Zhang, and co-workers constructed a pH- and temperature-responsive supramolecular diblock copolymer for drug delivery, which was obtained by the host–guest recognition of pillar[5]arene and viologen salts (Figure 10I) [173]. The supramolecular diblock copolymer could self-assemble into supramolecular nanoparticles, which were used for the encapsulation of PSs (pyropheophorbide-a, PhA) for PDT. When the pH value of the supramolecular nanoparticle solution was adjusted to 5, the cumulative release of PhA was 43% at 37 °C. At 25 °C, a burst release of PhA was observed within the first 2 h, and the cumulative release amount reached 82% within 11 h. This result suggested that the dual-responsive nanoparticles could effectively release PhA under pH and thermal stimulation (Figure 10II). Meanwhile, PhA-loaded nanoparticles showed a low dark toxicity to A549 cells (Figure 10III). This work paved the way for the application of a supramolecular diblock copolymer in PDT. Moreover, Li and co-workers designed and synthesized a pillar[5]arene-based nonionic supramolecular pseudoblock copolymer, which was assembled with β-cyclodextrin end-capped poly(acrylic acid) through host–guest interactions [174]. This supramolecular pseudoblock polymer could be used as a new platform for drug delivery and cancer therapy.

6. Conclusions

In summary, many remarkable pillararene-based supramolecular polymers have been developed for cancer therapy, ranging from linear supramolecular polymers, branched supramolecular polymers, to crosslinked supramolecular polymers and supramolecular block copolymers. Compared with the traditional polymer chemistry strategy of using stable and rigid covalent bonds, the construction of supramolecular polymers shows reversibility and dynamics. These properties provide the possibility to realize its stimulus responsiveness and endows supramolecular polymers with incomparable advantages such as reversibility, adaptiveness, and self-healing. In addition, the polymerization degree of supramolecular polymers can be adjusted by changing the structure, orientation, rigidity, and flexibility of monomers, thus realizing the controllable preparation of supramolecular polymers. These characteristics can effectively solve the problems faced by covalent polymers in the fields of bioimaging and drug carriers. However, many challenges remain to be addressed before these supramolecular polymers can be used for clinical applications.
(i) More efforts should be devoted to design new building blocks or develop new methods to expand the structure and type of pillararene-based supramolecular polymers. Especially, the combinatorial use of multiple noncovalent interactions deserves more attention.
(ii) Long-term monitoring of the organism is also essential. Based on the full use of imaging technology, diagnostic/imaging functions are integrated into supramolecular drugs to achieve precision therapy.
(iii) Developing novel targeted and stimuli-responsive drug delivery systems holds extraordinary potential in cancer therapy. In this way, some problems of traditional chemotherapeutic drugs can be overcome, such as poor water solubility, low therapeutic efficiency, and adverse effects on normal cells.
Although pillararene-based supramolecular polymers for clinical applications are still a long-standing challenge in biomedical development, scientists have made significant progress. It can be expected that pillararene-based supramolecular polymers will have a broad development prospect in the near future.

Author Contributions

Conceptualization, M.Y. and J.Z.; writing—original draft preparation, M.Y.; writing—review and editing, J.Z.; supervision, J.Z. All authors have read and agreed to the published version of the manuscript.

Funding

This work was supported by the National Natural Science Foundation of China (22101043), the Fundamental Research Funds for the Central Universities (N2205013) and Northeastern University.

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

Not applicable.

Conflicts of Interest

The authors declare no conflict of interest.

References

  1. Liu, Y.; Lv, S.; Liu, D.; Song, F. Recent development of amorphous metal coordination polymers for cancer therapy. Acta Biomater. 2020, 116, 16–31. [Google Scholar] [CrossRef] [PubMed]
  2. Zhou, J.; Yu, G.; Huang, F. Supramolecular chemotherapy based on host–guest molecular recognition: A novel strategy in the battle against cancer with a bright future. Chem. Soc. Rev. 2017, 46, 7021–7053. [Google Scholar] [CrossRef] [PubMed]
  3. Ding, C.; Chen, C.; Zeng, X.; Chen, H.; Zhao, Y. Emerging strategies in stimuli-responsive prodrug nanosystems for cancer therapy. ACS Nano 2022, 16, 13513–13553. [Google Scholar] [CrossRef] [PubMed]
  4. Yang, G.; Wang, D.; Phua, S.Z.F.; Bindra, A.K.; Qian, C.; Zhang, R.; Cheng, L.; Liu, G.; Wu, H.; Liu, Z.; et al. Albumin-based therapeutics capable of glutathione consumption and hydrogen peroxide generation for synergetic chemodynamic and chemotherapy of cancer. ACS Nano 2022, 16, 2319–2329. [Google Scholar] [CrossRef] [PubMed]
  5. Wang, H.; Xue, K.-F.; Yang, Y.; Hu, H.; Xu, J.-F.; Zhang, X. In Situ Hypoxia-Induced Supramolecular Perylene Diimide Radical Anions in Tumors for Photothermal Therapy with Improved Specificity. J. Am. Chem. Soc. 2022, 144, 2360–2367. [Google Scholar] [CrossRef]
  6. Yang, X.; Wu, B.; Zhou, J.; Lu, H.; Zhang, H.; Huang, F.; Wang, H. Controlling intracellular enzymatic self-assembly of peptide by host–guest complexation for programming cancer cell death. Nano Lett. 2022, 22, 7588–7596. [Google Scholar] [CrossRef]
  7. Song, N.; Zhang, Z.; Liu, P.; Yang, Y.-W.; Wang, L.; Wang, D.; Tang, B.Z. Nanomaterials with supramolecular assembly based on AIE luminogens for theranostic applications. Adv. Mater. 2020, 32, e2004208. [Google Scholar] [CrossRef]
  8. Zhang, X.; Chen, X.; Zhao, Y. Nanozymes: Versatile platforms for cancer diagnosis and therapy. Nano-Micro Lett. 2022, 14, 95. [Google Scholar] [CrossRef]
  9. Yang, J.; Wang, H.; Yin, Z.; Zhang, S.; Xu, J.-F.; Zhang, X. Emulsion interfacial polymerization of anticancer peptides: Fabricating polypeptide nanospheres with high drug-loading efficiency and enhanced anticancer activity. Sci. China Chem. 2022, 65, 2252–2259. [Google Scholar] [CrossRef]
  10. Shen, J.; Wang, Q.; Lv, Y.; Dong, J.; Xuan, G.; Yang, J.; Wu, D.; Zhou, J.; Yu, G.; Tang, G.; et al. Nanomedicine fabricated from a boron-dipyrromethene (BODIPY)-embedded amphiphilic copolymer for photothermal-enhanced chemotherapy. ACS Biomater. Sci. Eng. 2019, 5, 4463–4473. [Google Scholar] [CrossRef]
  11. Zhou, J.; Rao, L.; Yu, G.; Cook, T.R.; Chen, X.; Huang, F. Supramolecular cancer nanotheranostics. Chem. Soc. Rev. 2021, 50, 2839–2891. [Google Scholar] [CrossRef] [PubMed]
  12. Yu, G.; Zhou, J.; Shen, J.; Tang, G.; Huang, F. Cationic pillar[6]arene/ATP host–guest recognition: Selectivity, inhibition of ATP hydrolysis, and application in multidrug resistance treatment. Chem. Sci. 2016, 7, 4073–4078. [Google Scholar] [CrossRef] [PubMed]
  13. Wang, J.; Zhang, B.; Sun, J.; Hu, W.; Wang, H. Recent advances in porous nanostructures for cancer theranostics. Nano Today 2021, 38, 101146. [Google Scholar] [CrossRef] [PubMed]
  14. Yue, L.; Yang, K.; Lou, X.-Y.; Yang, Y.-W.; Wang, R. Versatile roles of macrocycles in organic-inorganic hybrid materials for biomedical applications. Matter 2020, 3, 1557–1588. [Google Scholar] [CrossRef]
  15. Pothig, A.; Casini, A. Recent developments of supramolecular metal-based structures for applications in cancer therapy and imaging. Theranostics 2019, 9, 3150–3169. [Google Scholar] [CrossRef]
  16. Yin, H.; Zhang, X.; Wei, J.; Lu, S.; Bardelang, D.; Wang, R. Recent advances in supramolecular antidotes. Theranostics 2021, 11, 1513–1526. [Google Scholar] [CrossRef]
  17. Qin, S.Y.; Zhang, A.Q.; Zhang, X.Z. Recent advances in targeted tumor chemotherapy based on smart nanomedicines. Small 2018, 14, e1802417. [Google Scholar] [CrossRef]
  18. Li, B.; Zhao, M.; Lin, J.; Huang, P.; Chen, X. Management of fluorescent organic/inorganic nanohybrids for biomedical applications in the NIR-II region. Chem. Soc. Rev. 2022, 51, 7692–7714. [Google Scholar] [CrossRef]
  19. Ding, Y.; Tong, Z.; Jin, L.; Ye, B.; Zhou, J.; Sun, Z.; Yang, H.; Hong, L.; Huang, F.; Wang, W.; et al. An NIR discrete metallacycle constructed from perylene bisimide and tetraphenylethylene fluorophores for imaging-guided cancer radio-chemotherapy. Adv. Mater. 2022, 34, 2106388. [Google Scholar] [CrossRef]
  20. Zhou, J.; Zhang, Y.; Yu, G.; Crawley, M.R.; Fulong, C.R.P.; Friedman, A.E.; Sengupta, S.; Sun, J.; Li, Q.; Huang, F.; et al. Highly emissive self-assembled BODIPY-platinum supramolecular triangles. J. Am. Chem. Soc. 2018, 140, 7730–7736. [Google Scholar] [CrossRef]
  21. Yang, K.; Yang, Z.; Yu, G.; Nie, Z.; Wang, R.; Chen, X. Polyprodrug nanomedicines: An emerging paradigm for cancer therapy. Adv. Mater. 2022, 34, 2107434. [Google Scholar] [CrossRef] [PubMed]
  22. Li, Z.; Song, N.; Yang, Y.-W. Stimuli-responsive drug-delivery systems based on supramolecular nanovalves. Matter 2019, 1, 345–368. [Google Scholar] [CrossRef]
  23. Wang, L.; Li, L.-L.; Fan, Y.-S.; Wang, H. Host−guest supramolecular nanosystems for cancer diagnostics and therapeutics. Adv. Mater. 2013, 25, 3888–3898. [Google Scholar] [CrossRef] [PubMed]
  24. Ma, Z.; Zhang, Y.; Dai, X.; Zhang, W.; Foda, M.F.; Zhang, J.; Zhao, Y.; Han, H. Selective thrombosis of tumor for enhanced hypoxia-activated prodrug therapy. Adv. Mater. 2021, 33, 2104504. [Google Scholar] [CrossRef]
  25. Liu, C.; Liu, X.; Xiang, X.; Pang, X.; Chen, S.; Zhang, Y.; Ren, E.; Zhang, L.; Liu, X.; Lv, P.; et al. A nanovaccine for antigen self-presentation and immunosuppression reversal as a personalized cancer immunotherapy strategy. Nat. Nanotechnol. 2022, 17, 531–540. [Google Scholar] [CrossRef]
  26. Zhou, J.; Yu, G.; Yang, J.; Shi, B.; Ye, B.; Wang, M.; Huang, F.; Stang, P.J. Polymeric nanoparticles integrated from discrete organoplatinum(II) metallacycle by stepwise post-assembly polymerization for synergistic cancer therapy. Chem. Mater. 2020, 32, 4564–4573. [Google Scholar] [CrossRef]
  27. Yu, G.; Zhu, B.; Shao, L.; Zhou, J.; Saha, M.L.; Shi, B.; Zhang, Z.; Hong, T.; Li, S.; Chen, X.; et al. Host−guest complexation-mediated codelivery of anticancer drug and photosensitizer for cancer photochemotherapy. Proc. Natl. Acad. Sci. USA 2019, 116, 6618–6623. [Google Scholar] [CrossRef]
  28. Yang, K.; Hua, B.; Qi, S.; Bai, B.; Yu, C.; Huang, F.; Yu, G. Suprasomes based on host–guest molecular recognition: An excellent alternative to liposomes in cancer theranostics. Angew. Chem. Int. Ed. 2022, 61, e202213572. [Google Scholar]
  29. Tang, B.; Li, W.-L.; Chang, Y.; Yuan, B.; Wu, Y.; Zhang, M.-T.; Xu, J.-F.; Li, J.; Zhang, X. A supramolecular radical dimer: High-efficiency NIR-II photothermal conversion and therapy. Angew. Chem. Int. Ed. 2019, 58, 15526–15531. [Google Scholar] [CrossRef]
  30. Li, X.; Bai, H.; Yang, Y.; Yoon, J.; Wang, S.; Zhang, X. Supramolecular antibacterial materials for combatting antibiotic resistance. Adv. Mater. 2019, 31, 1805092. [Google Scholar] [CrossRef]
  31. Tian, R.; Feng, X.; Wei, L.; Dai, D.; Ma, Y.; Pan, H.; Ge, S.; Bai, L.; Ke, C.; Liu, Y.; et al. A genetic engineering strategy for editing near-infrared-II fluorophores. Nat. Commun. 2022, 13, 2853. [Google Scholar] [CrossRef]
  32. Yan, Z.-J.; Li, Y.-W.; Yang, M.; Fu, Y.-H.; Wen, R.; Wang, W.; Li, Z.-T.; Zhang, Y.; Hou, J.-L. Voltage-driven flipping of zwitterionic artificial channels in lipid bilayers to rectify ion transport. J. Am. Chem. Soc. 2021, 143, 11332–11336. [Google Scholar] [CrossRef]
  33. Yan, Z.-J.; Wang, D.; Ye, Z.; Fan, T.; Wu, G.; Deng, L.; Yang, L.; Li, B.; Liu, J.; Ma, T.; et al. Artificial aquaporin that restores wound healing of impaired cells. J. Am. Chem. Soc. 2020, 142, 15638–15643. [Google Scholar] [CrossRef] [PubMed]
  34. Yan, M.; Zhou, J. Suprasomes: An emerging platform for cancer theranostics. Sci. China Chem. 2023, 66. [Google Scholar] [CrossRef]
  35. Cheng, H.-B.; Zhang, Y.-M.; Liu, Y.; Yoon, J. Turn-on supramolecular host–guest nanosystems as theranostics for cancer. Chem 2019, 5, 553–574. [Google Scholar] [CrossRef]
  36. Sheehan, F.; Sementa, D.; Jain, A.; Kumar, M.; Tayarani-Najjaran, M.; Kroiss, D.; Ulijn, R.V. Peptide-based supramolecular systems chemistry. Chem. Rev. 2021, 121, 13869–13914. [Google Scholar] [CrossRef] [PubMed]
  37. Song, Q.; Cheng, Z.; Kariuki, M.; Hall, S.C.L.; Hill, S.K.; Rho, J.Y.; Perrier, S. Molecular self-assembly and supramolecular chemistry of cyclic peptides. Chem. Rev. 2021, 121, 13936–13995. [Google Scholar] [CrossRef]
  38. Olivo, G.; Capocasa, G.; Del Giudice, D.; Lanzalunga, O.; Di Stefano, S. New horizons for catalysis disclosed by supramolecular chemistry. Chem. Soc. Rev. 2021, 50, 7681–7724. [Google Scholar] [CrossRef] [PubMed]
  39. González-Cuesta, M.; Ortiz Mellet, C.; García Fernández, J.M. Carbohydrate supramolecular chemistry: Beyond the multivalent effect. Chem. Commun. 2020, 56, 5207–5222. [Google Scholar] [CrossRef] [PubMed]
  40. Yao, H.; Ke, H.; Zhang, X.; Pan, S.-J.; Li, M.-S.; Yang, L.-P.; Schreckenbach, G.; Jiang, W. Molecular recognition of hydrophilic molecules in water by combining the hydrophobic effect with hydrogen bonding. J. Am. Chem. Soc. 2018, 140, 13466–13477. [Google Scholar] [CrossRef]
  41. Yu, G.; Zhao, X.; Zhou, J.; Mao, Z.; Huang, X.; Wang, Z.; Hua, B.; Liu, Y.; Zhang, F.; He, Z.; et al. Supramolecular polymer-based nanomedicine: High therapeutic performance and negligible long-term immunotoxicity. J. Am. Chem. Soc. 2018, 140, 8005–8019. [Google Scholar] [CrossRef]
  42. Wang, Z.; Sun, C.; Yang, K.; Chen, X.; Wang, R. Cucurbituril-based supramolecular polymers for biomedical applications. Angew. Chem. Int. Ed. 2022, 61, e202206763. [Google Scholar]
  43. Sharko, A.; Livitz, D.; De Piccoli, S.; Bishop, K.J.M.; Hermans, T.M. Insights into chemically fueled supramolecular polymers. Chem. Rev. 2022, 122, 11759–11777. [Google Scholar] [CrossRef] [PubMed]
  44. Zhu, Y.; Zheng, W.; Wang, W.; Yang, H.-B. When polymerization meets coordination-driven self-assembly: Metallo-supramolecular polymers based on supramolecular coordination complexes. Chem. Soc. Rev. 2021, 50, 7395–7417. [Google Scholar] [CrossRef] [PubMed]
  45. Brunsveld, L.; Folmer, B.J.B.; Meijer, E.W.; Sijbesma, R.P. Supramolecular polymers. Chem. Rev. 2001, 101, 4071–4098. [Google Scholar] [CrossRef]
  46. Qin, B.; Yin, Z.; Tang, X.; Zhang, S.; Wu, Y.; Xu, J.-F.; Zhang, X. Supramolecular polymer chemistry: From structural control to functional assembly. Prog. Polym. Sci. 2020, 100, 101167. [Google Scholar] [CrossRef]
  47. Qin, B.; Zhang, S.; Song, Q.; Huang, Z.; Xu, J.-F.; Zhang, X. Supramolecular interfacial polymerization: A controllable method of fabricating supramolecular polymeric materials. Angew. Chem. Int. Ed. 2017, 56, 7639–7643. [Google Scholar] [CrossRef]
  48. Gu, P.-Y.; Chai, Y.; Hou, H.; Xie, G.; Jiang, Y.; Xu, Q.-F.; Liu, F.; Ashby, P.D.; Lu, J.-M.; Russell, T.P. Stabilizing liquids using interfacial supramolecular polymerization. Angew. Chem. Int. Ed. 2019, 58, 12112–12116. [Google Scholar] [CrossRef]
  49. Groombridge, A.S.; Palma, A.; Parker, R.M.; Abell, C.; Scherman, O.A. Aqueous interfacial gels assembled from small molecule supramolecular polymers. Chem. Sci. 2017, 8, 1350–1355. [Google Scholar] [CrossRef]
  50. Folmer, B.J.B.; Sijbesma, R.P.; Versteegen, R.M.; van der Rijt, J.A.J.; Meijer, E.W. Supramolecular polymer materials: Chain extension of telechelic polymers using a reactive hydrogen-bonding synthon. Adv. Mater. 2000, 12, 874–878. [Google Scholar] [CrossRef]
  51. Wang, Y.; Xu, H.; Zhang, X. Tuning the amphiphilicity of building blocks: Controlled self-assembly and disassembly for functional supramolecular materials. Adv. Mater. 2009, 21, 2849–2864. [Google Scholar] [CrossRef]
  52. Yang, K.; Qi, S.; Yu, X.; Bai, B.; Zhang, X.; Mao, Z.; Huang, F.; Yu, G. A hybrid supramolecular polymeric banomedicine for cascade-amplified synergetic cancer therapy. Angew. Chem. Int. Ed. 2022, 61, e202203786. [Google Scholar]
  53. Jin, W.; Wang, Q.; Wu, M.; Li, Y.; Tang, G.; Ping, Y.; Chu, P.K. Lanthanide-integrated supramolecular polymeric nanoassembly with multiple regulation characteristics for multidrug-resistant cancer therapy. Biomaterials 2017, 129, 83–97. [Google Scholar] [CrossRef] [PubMed]
  54. Voorhaar, L.; Hoogenboom, R. Supramolecular polymer networks: Hydrogels and bulk materials. Chem. Soc. Rev. 2016, 45, 4013–4031. [Google Scholar] [CrossRef]
  55. Krieg, E.; Bastings, M.M.C.; Besenius, P.; Rybtchinski, B. Supramolecular polymers in aqueous media. Chem. Rev. 2016, 116, 2414–2477. [Google Scholar] [CrossRef]
  56. Zhang, W.; Yang, W.; Chen, J.; Wang, Y.; Yan, M.; Zhou, J. An amphiphilic water-soluble biphen[3]arene with a tunable lower critical solution temperature behavior. New J. Chem. 2022, 46, 21453–21457. [Google Scholar] [CrossRef]
  57. Ge, Z.; Hu, J.; Huang, F.; Liu, S. Responsive supramolecular gels constructed by crown ether based molecular recognition. Angew. Chem. Int. Ed. 2009, 48, 1798–1802. [Google Scholar] [CrossRef]
  58. Yan, X.; Wang, F.; Zheng, B.; Huang, F. Stimuli-responsive supramolecular polymeric materials. Chem. Soc. Rev. 2012, 41, 6042–6065. [Google Scholar] [CrossRef]
  59. Nie, H.; Wei, Z.; Ni, X.L.; Liu, Y. Assembly and applications of macrocyclic-confinement-derived supramolecular organic luminescent emissions from cucurbiturils. Chem. Rev. 2022, 122, 9032–9077. [Google Scholar] [CrossRef]
  60. Liu, Z.; Liu, Y. Multicharged cyclodextrin supramolecular assemblies. Chem. Soc. Rev. 2022, 51, 4786–4827. [Google Scholar] [CrossRef]
  61. Pan, Y.-C.; Hu, X.-Y.; Guo, D.-S. Biomedical applications of calixarenes: State of the art and perspectives. Angew. Chem. Int. Ed. 2021, 60, 2768–2794. [Google Scholar] [CrossRef] [PubMed]
  62. Liang, Y.; Li, E.; Wang, K.; Guan, Z.-J.; He, H.-H.; Zhang, L.; Zhou, H.-C.; Huang, F.; Fang, Y. Organo-macrocycle-containing hierarchical metal–organic frameworks and cages: Design, structures, and applications. Chem. Soc. Rev. 2022, 51, 8378–8405. [Google Scholar] [CrossRef] [PubMed]
  63. Zhang, Y.-M.; Liu, Y.-H.; Liu, Y. Cyclodextrin-based multistimuli-responsive supramolecular assemblies and their biological functions. Adv. Mater. 2020, 32, 1806158. [Google Scholar] [CrossRef]
  64. Guo, D.-S.; Liu, Y. Calixarene-based supramolecular polymerization in solution. Chem. Soc. Rev. 2012, 41, 5907–5921. [Google Scholar] [CrossRef]
  65. Zhang, Z.; Yue, Y.-X.; Xu, L.; Wang, Y.; Geng, W.-C.; Li, J.-J.; Kong, X.-l.; Zhao, X.; Zheng, Y.; Zhao, Y.; et al. Macrocyclic-amphiphile-based self-assembled nanoparticles for ratiometric delivery of therapeutic combinations to tumors. Adv. Mater. 2021, 33, 2007719. [Google Scholar] [CrossRef] [PubMed]
  66. Li, Z.; Yang, Y.-W. Macrocycle-based porous organic polymers for separation, sensing, and catalysis. Adv. Mater. 2022, 34, 2107401. [Google Scholar] [CrossRef]
  67. Zhou, J.; Yu, G.; Li, Y.; Shen, J.; Wang, M.; Li, Z.; Wei, P.; Tang, J.; Huang, F. [2]Pseudorotaxane-based supramolecular optical indicator for the visual detection of cellular cyanide excretion. Chem. A Eur. J. 2019, 25, 14447–14453. [Google Scholar] [CrossRef]
  68. Ni, X.-L.; Xiao, X.; Cong, H.; Zhu, Q.-J.; Xue, S.-F.; Tao, Z. Self-assemblies based on the “outer-surface interactions” of cucurbit[n]urils: New opportunities for supramolecular architectures and materials. Acc. Chem. Res. 2014, 47, 1386–1395. [Google Scholar] [CrossRef]
  69. Wang, M.; Fang, S.; Yang, S.; Li, Q.; Khashab, N.M.; Zhou, J.; Huang, F. Separation of ethyltoluene isomers by nonporous adaptive crystals of perethylated and perbromoethylated pillararenes. Mater. Today Chem. 2022, 24, 100919. [Google Scholar] [CrossRef]
  70. Zhou, J.; Yu, G.; Li, Q.; Wang, M.; Huang, F. Separation of benzene and cyclohexane by nonporous adaptive crystals of a hybrid[3]arene. J. Am. Chem. Soc. 2020, 142, 2228–2232. [Google Scholar] [CrossRef]
  71. Wu, D.; Li, Y.; Yang, J.; Shen, J.; Zhou, J.; Hu, Q.; Yu, G.; Tang, G.; Chen, X. Supramolecular nanomedicine constructed from cucurbit[8]uril-based amphiphilic brush copolymer for cancer therapy. ACS Appl. Mater. Interfaces 2017, 9, 44392–44401. [Google Scholar] [CrossRef] [PubMed]
  72. Tang, R.; Ye, Y.; Zhu, S.; Wang, Y.; Lu, B.; Yao, Y. Pillar[6]arenes: From preparation, host–guest property to self-assembly and applications. Chin. Chem. Lett. 2023, 34, 107734. [Google Scholar] [CrossRef]
  73. Song, N.; Lou, X.-Y.; Ma, L.; Gao, H.; Yang, Y.-W. Supramolecular nanotheranostics based on pillarenes. Theranostics 2019, 9, 3075–3093. [Google Scholar] [CrossRef] [PubMed]
  74. Xu, X.; Jerca, V.V.; Hoogenboom, R. Structural diversification of pillar[n]arene macrocycles. Angew. Chem. Int. Ed. 2020, 59, 6314–6316. [Google Scholar] [CrossRef] [PubMed]
  75. Yang, K.; Pei, Y.; Wen, J.; Pei, Z. Recent advances in pillar[n]arenes: Synthesis and applications based on host–guest interactions. Chem. Commun. 2016, 52, 9316–9326. [Google Scholar] [CrossRef]
  76. Li, Z.; Yang, Y.-W. Functional materials with pillarene struts. Acc. Mater. Res. 2021, 2, 292–305. [Google Scholar] [CrossRef]
  77. Li, Y.-F.; Li, Z.; Lin, Q.; Yang, Y.-W. Functional supramolecular gels based on pillar[n]arene macrocycles. Nanoscale 2020, 12, 2180–2200. [Google Scholar] [CrossRef]
  78. Song, N.; Kakuta, T.; Yamagishi, T.-a.; Yang, Y.-W.; Ogoshi, T. Molecular-scale porous materials based on pillar[n]arenes. Chem 2018, 4, 2029–2053. [Google Scholar] [CrossRef]
  79. Song, N.; Zhang, Z.; Liu, P.; Dai, D.; Chen, C.; Li, Y.; Wang, L.; Han, T.; Yang, Y.-W.; Wang, D.; et al. Pillar[5]arene-modified gold nanorods as nanocarriers for multi-modal imaging-guided synergistic photodynamic-photothermal therapy. Adv. Funct. Mater. 2021, 31, 2009924. [Google Scholar] [CrossRef]
  80. Braegelman, A.S.; Webber, M.J. Integrating stimuli-responsive properties in host–guest supramolecular drug delivery systems. Theranostics 2019, 9, 3017–3040. [Google Scholar] [CrossRef]
  81. Goor, O.J.G.M.; Hendrikse, S.I.S.; Dankers, P.Y.W.; Meijer, E.W. From supramolecular polymers to multi-component biomaterials. Chem. Soc. Rev. 2017, 46, 6621–6637. [Google Scholar] [CrossRef] [PubMed]
  82. Clemons, T.D.; Stupp, S.I. Design of materials with supramolecular polymers. Prog. Polym. Sci. 2020, 111, 101310. [Google Scholar] [CrossRef] [PubMed]
  83. Li, C.; Iscen, A.; Sai, H.; Sato, K.; Sather, N.A.; Chin, S.M.; Álvarez, Z.; Palmer, L.C.; Schatz, G.C.; Stupp, S.I. Supramolecular–covalent hybrid polymers for light-activated mechanical actuation. Nat. Mater. 2020, 19, 900–909. [Google Scholar] [CrossRef] [PubMed]
  84. Lou, X.-Y.; Yang, Y.-W. Pillar[n]arene-based supramolecular switches in solution and on surfaces. Adv. Mater. 2020, 32, 2003263. [Google Scholar] [CrossRef] [PubMed]
  85. Zhang, H.; Liu, Z.; Zhao, Y. Pillararene-based self-assembled amphiphiles. Chem. Soc. Rev. 2018, 47, 5491–5528. [Google Scholar] [CrossRef] [PubMed]
  86. de Greef, T.F.A.; Meijer, E.W. Supramolecular polymers. Nature 2008, 453, 171–173. [Google Scholar] [CrossRef] [PubMed]
  87. Yang, L.; Tan, X.; Wang, Z.; Zhang, X. Supramolecular polymers: Historical development, preparation, characterization, and functions. Chem. Rev. 2015, 115, 7196–7239. [Google Scholar] [CrossRef]
  88. Dong, R.; Zhou, Y.; Huang, X.; Zhu, X.; Lu, Y.; Shen, J. Functional supramolecular polymers for biomedical applications. Adv. Mater. 2015, 27, 498–526. [Google Scholar] [CrossRef]
  89. Wang, F.; Zhang, J.; Ding, X.; Dong, S.; Liu, M.; Zheng, B.; Li, S.; Wu, L.Z.; Yu, Y.; Gibson, H.W.; et al. Metal coordination mediated reversible conversion between linear and cross-linked supramolecular polymers. Angew. Chem. Int. Ed. 2010, 49, 1108–1112. [Google Scholar] [CrossRef]
  90. Harada, A.; Takashima, Y.; Yamaguchi, H. Cyclodextrin-based supramolecular polymers. Chem. Soc. Rev. 2009, 38, 875–882. [Google Scholar] [CrossRef]
  91. Yebeutchou, R.M.; Tancini, F.; Demitri, N.; Geremia, S.; Mendichi, R.; Dalcanale, E. Host–guest driven self-assembly of linear and star supramolecular polymers. Angew. Chem. Int. Ed. 2008, 47, 4504–4508. [Google Scholar] [CrossRef] [PubMed]
  92. Wang, Y.; Jin, M.; Chen, Z.; Hu, X.; Pu, L.; Pei, Z.; Pei, Y. Tumor microenvironment responsive supramolecular glyco-nanovesicles based on diselenium-bridged pillar[5]arene dimer for targeted chemotherapy. Chem. Commun. 2020, 56, 10642–10645. [Google Scholar] [CrossRef] [PubMed]
  93. Yu, G.; Zhou, J.; Chi, X. Pillar[10]arene-based size-selective host–guest complexation and its application in tuning the LCST behavior of a thermoresponsive polymer. Macromol. Rapid Commun. 2015, 36, 23–30. [Google Scholar] [CrossRef]
  94. Xia, D.; Wang, P.; Ji, X.; Khashab, N.M.; Sessler, J.L.; Huang, F. Functional supramolecular polymeric networks: The marriage of covalent polymers and macrocycle-based host–guest interactions. Chem. Rev. 2020, 120, 6070–6123. [Google Scholar] [CrossRef] [PubMed]
  95. Budak, A.; Aydogan, A. A calix[4]pyrrole-based linear supramolecular polymer constructed by orthogonal self-assembly. Chem. Commun. 2021, 57, 4186–4189. [Google Scholar] [CrossRef] [PubMed]
  96. Zhao, W.; Qiao, B.; Tropp, J.; Pink, M.; Azoulay, J.D.; Flood, A.H. Linear supramolecular polymers driven by anion–anion dimerization of difunctional phosphonate monomers inside cyanostar macrocycles. J. Am. Chem. Soc. 2019, 141, 4980–4989. [Google Scholar] [CrossRef]
  97. Zhou, W.-L.; Chen, Y.; Yu, Q.; Zhang, H.; Liu, Z.-X.; Dai, X.-Y.; Li, J.-J.; Liu, Y. Ultralong purely organic aqueous phosphorescence supramolecular polymer for targeted tumor cell imaging. Nat. Commun. 2020, 11, 4655. [Google Scholar] [CrossRef]
  98. Li, H.; Yang, Y.; Xu, F.; Liang, T.; Wen, H.; Tian, W. Pillararene-based supramolecular polymers. Chem. Commun. 2019, 55, 271–285. [Google Scholar] [CrossRef]
  99. Lan, M.; Zhao, S.; Liu, W.; Lee, C.-S.; Zhang, W.; Wang, P. Photosensitizers for photodynamic therapy. Adv. Healthc. Mater. 2019, 8, 1900132. [Google Scholar] [CrossRef]
  100. Liu, Y.; Meng, X.; Bu, W. Upconversion-based photodynamic cancer therapy. Coord. Chem. Rev. 2019, 379, 82–98. [Google Scholar] [CrossRef]
  101. Wei, F.; Rees, T.W.; Liao, X.; Ji, L.; Chao, H. Oxygen self-sufficient photodynamic therapy. Coord. Chem. Rev. 2021, 432, 213714. [Google Scholar] [CrossRef]
  102. Nguyen, V.-N.; Yan, Y.; Zhao, J.; Yoon, J. Heavy-atom-free photosensitizers: From molecular design to applications in the photodynamic therapy of cancer. Acc. Chem. Res. 2021, 54, 207–220. [Google Scholar] [CrossRef] [PubMed]
  103. Li, X.; Kwon, N.; Guo, T.; Liu, Z.; Yoon, J. Innovative strategies for hypoxic-tumor photodynamic therapy. Angew. Chem. Int. Ed. 2018, 57, 11522–11531. [Google Scholar] [CrossRef] [PubMed]
  104. Zhao, Y.-Y.; Zhang, L.; Chen, Z.; Zheng, B.-Y.; Ke, M.; Li, X.; Huang, J.-D. Nanostructured phthalocyanine assemblies with efficient synergistic effect of type I photoreaction and photothermal action to overcome tumor hypoxia in photodynamic therapy. J. Am. Chem. Soc. 2021, 143, 13980–13989. [Google Scholar] [CrossRef]
  105. Yuan, H.; Han, Z.; Chen, Y.; Qi, F.; Fang, H.; Guo, Z.; Zhang, S.; He, W. Ferroptosis photoinduced by new cyclometalated iridium(III) complexes and its synergism with apoptosis in tumor cell inhibition. Angew. Chem. Int. Ed. 2021, 60, 8174–8181. [Google Scholar] [CrossRef]
  106. Teng, K.X.; Niu, L.Y.; Yang, Q.Z. A host–guest strategy for converting the photodynamic agents from a singlet oxygen generator to a superoxide radical generator. Chem. Sci. 2022, 13, 5951–5956. [Google Scholar] [CrossRef] [PubMed]
  107. He, C.; Lu, J.; Lin, W. Hybrid nanoparticles for combination therapy of cancer. J. Control. Release 2015, 219, 224–236. [Google Scholar] [CrossRef] [PubMed]
  108. Lehár, J.; Krueger, A.S.; Avery, W.; Heilbut, A.M.; Johansen, L.M.; Price, E.R.; Rickles, R.J.; Short Iii, G.F.; Staunton, J.E.; Jin, X.; et al. Synergistic drug combinations tend to improve therapeutically relevant selectivity. Nat. Biotechnol. 2009, 27, 659–666. [Google Scholar] [CrossRef] [PubMed]
  109. Shao, L.; Hu, T.; Fan, X.; Wu, X.; Zhou, F.; Chen, B.; Tan, S.; Xu, H.; Pan, A.; Liang, S.; et al. Intelligent nanoplatform with multi therapeutic modalities for synergistic cancer therapy. ACS Appl. Mater. Interfaces 2022, 14, 13122–13135. [Google Scholar] [CrossRef]
  110. Sarah, C. Identifying synergistic drug combinations. Nat. Rev. Drug Discov. 2017, 16, 314. [Google Scholar] [CrossRef]
  111. Wang, J.; Wang, D.; Cen, M.; Jing, D.; Bei, J.; Huang, Y.; Zhang, J.; Lu, B.; Wang, Y.; Yao, Y. GOx-assisted synthesis of pillar[5]arene based supramolecular polymeric nanoparticles for targeted/synergistic chemo-chemodynamic cancer therapy. J. Nanobiotechnol. 2022, 20, 33. [Google Scholar] [CrossRef] [PubMed]
  112. Aida, T.; Meijer, E.W.; Stupp, S.I. Functional supramolecular polymers. Science 2012, 335, 813–817. [Google Scholar] [CrossRef] [PubMed]
  113. Dong, R.; Zhou, Y.; Zhu, X. Supramolecular dendritic polymers: From synthesis to applications. Acc. Chem. Res. 2014, 47, 2006–2016. [Google Scholar] [CrossRef]
  114. Liu, K.; Jiang, Y.; Bao, Z.; Yan, X. Skin-inspired electronics enabled by supramolecular polymeric materials. CCS Chem. 2019, 1, 431–447. [Google Scholar] [CrossRef]
  115. Krishnamoorthy, M.; Hakobyan, S.; Ramstedt, M.; Gautrot, J.E. Surface-initiated polymer brushes in the biomedical field: Applications in membrane science, biosensing, cell culture, regenerative medicine and antibacterial coatings. Chem. Rev. 2014, 114, 10976–11026. [Google Scholar] [CrossRef] [PubMed]
  116. Müllner, M.; Dodds, S.J.; Nguyen, T.-H.; Senyschyn, D.; Porter, C.J.H.; Boyd, B.J.; Caruso, F. Size and rigidity of cylindrical polymer brushes dictate long circulating properties in vivo. ACS Nano 2015, 9, 1294–1304. [Google Scholar] [CrossRef]
  117. Chen, Y.; Kushner, A.M.; Williams, G.A.; Guan, Z. Multiphase design of autonomic self-healing thermoplastic elastomers. Nat. Chem. 2012, 4, 467–472. [Google Scholar] [CrossRef]
  118. Verduzco, R.; Li, X.; Pesek, S.L.; Stein, G.E. Structure, function, self-assembly, and applications of bottlebrush copolymers. Chem. Soc. Rev. 2015, 44, 2405–2420. [Google Scholar] [CrossRef]
  119. Li, S.-L.; Xiao, T.; Lin, C.; Wang, L. Advanced supramolecular polymers constructed by orthogonal self-assembly. Chem. Soc. Rev. 2012, 41, 5950–5968. [Google Scholar] [CrossRef]
  120. Liu, Y.; Pauloehrl, T.; Presolski, S.I.; Albertazzi, L.; Palmans, A.R.A.; Meijer, E.W. Modular synthetic platform for the construction of functional single-chain polymeric nanoparticles: From aqueous catalysis to photosensitization. J. Am. Chem. Soc. 2015, 137, 13096–13105. [Google Scholar] [CrossRef]
  121. Wei, J.; Liu, Y.; Yu, J.; Chen, L.; Luo, M.; Yang, L.; Li, P.; Li, S.; Zhang, X.-H. Conjugated polymers: Optical toolbox for bioimaging and cancer therapy. Small 2021, 17, e2103127. [Google Scholar] [CrossRef] [PubMed]
  122. Yu, G.; Zhao, R.; Wu, D.; Zhang, F.; Shao, L.; Zhou, J.; Yang, J.; Tang, G.; Chen, X.; Huang, F. Pillar[5]arene-based amphiphilic supramolecular brush copolymer: Fabrication, controllable self-assembly and application in self-imaging targeted drug delivery. Polym. Chem. 2016, 7, 6178–6188. [Google Scholar] [CrossRef] [PubMed]
  123. Sun, H.; Kabb, C.P.; Sims, M.B.; Sumerlin, B.S. Architecture-transformable polymers: Reshaping the future of stimuli-responsive polymers. Prog. Polym. Sci. 2019, 89, 61–75. [Google Scholar] [CrossRef]
  124. Tian, Q.; Fei, C.; Yin, H.; Feng, Y. Stimuli-responsive polymer wormlike micelles. Prog. Polym. Sci. 2019, 89, 108–132. [Google Scholar] [CrossRef]
  125. Lugger, S.J.D.; Houben, S.J.A.; Foelen, Y.; Debije, M.G.; Schenning, A.P.H.J.; Mulder, D.J. Hydrogen-bonded supramolecular liquid crystal polymers: Smart materials with stimuli-responsive, self-healing, and recyclable properties. Chem. Rev. 2022, 122, 4946–4975. [Google Scholar] [CrossRef] [PubMed]
  126. Lu, W.; Le, X.; Zhang, J.; Huang, Y.; Chen, T. Supramolecular shape memory hydrogels: A new bridge between stimuli-responsive polymers and supramolecular chemistry. Chem. Soc. Rev. 2017, 46, 1284–1294. [Google Scholar] [CrossRef] [PubMed]
  127. Zhang, J.; He, B.; Hu, Y.; Alam, P.; Zhang, H.; Lam, J.W.Y.; Tang, B.Z. Stimuli-responsive AIEgens. Adv. Mater. 2021, 33, 2008071. [Google Scholar] [CrossRef]
  128. Zhang, K.Y.; Liu, S.; Zhao, Q.; Huang, W. Stimuli–responsive metallopolymers. Coord. Chem. Rev. 2016, 319, 180–195. [Google Scholar] [CrossRef]
  129. Zola, R.S.; Bisoyi, H.K.; Wang, H.; Urbas, A.M.; Bunning, T.J.; Li, Q. Dynamic control of light direction enabled by stimuli-responsive liquid crystal gratings. Adv. Mater. 2019, 31, 1806172. [Google Scholar] [CrossRef]
  130. Kim, J.; Kim, H.; Kim, W.J. Gene delivery: Single-layered MoS2–PEI–PEG nanocomposite-mediated gene delivery controlled by photo and redox stimuli. Small 2016, 12, 1183. [Google Scholar] [CrossRef]
  131. Isayama, K.; Aizawa, N.; Kim, J.Y.; Yasuda, T. Modulating photo- and electroluminescence in a stimuli-responsive π-conjugated donor–acceptor molecular system. Angew. Chem. Int. Ed. 2018, 57, 11982–11986. [Google Scholar] [CrossRef] [PubMed]
  132. Zhou, J.; Xu, H.; Tong, Z.; Yang, Y.; Jiang, G. Photo/pH-controlled host–guest interaction between an azobenzene-containing block copolymer and water-soluble pillar[6]arene as a strategy to construct the “compound vesicles” for controlled drug delivery. Mater. Sci. Eng. C 2018, 89, 237–244. [Google Scholar] [CrossRef] [PubMed]
  133. Ninio-Many, L.; Buchshtab, N.; Slutskin, I.V.; Weiner, I.; Yahav, S.; Berko-Ashur, D.; Nicenboim, J.; Zelcbuch, L.; Gartman, E.S.; Kahan-Hanum, M.; et al. 82P Novel analysis of F. nucleatum subspecies in human CRC tissue and engineering of therapeutic F. nucleatum phage. Ann. Oncol. 2020, 31, S1450. [Google Scholar] [CrossRef]
  134. Yu, T.; Guo, F.; Yu, Y.; Sun, T.; Ma, D.; Han, J.; Qian, Y.; Kryczek, I.; Sun, D.; Nagarsheth, N.; et al. Fusobacterium nucleatum promotes chemoresistance to colorectal cancer by modulating autophagy. Cell 2017, 170, 548–563.e16. [Google Scholar] [CrossRef]
  135. Bullman, S.; Pedamallu, C.S.; Sicinska, E.; Clancy, T.E.; Zhang, X.; Cai, D.; Neuberg, D.; Huang, K.; Guevara, F.; Nelson, T.; et al. Analysis of fusobacterium persistence and antibiotic response in colorectal cancer. Science 2017, 358, 1443–1448. [Google Scholar] [CrossRef]
  136. Liu, H.; Yang, J.; Yan, X.; Li, C.; Elsabahy, M.; Chen, L.; Yang, Y.-W.; Gao, H. A dendritic polyamidoamine supramolecular system composed of pillar[5]arene and azobenzene for targeting drug-resistant colon cancer. J. Mater. Chem. B 2021, 9, 9594–9605. [Google Scholar] [CrossRef]
  137. Hu, Q.; Li, H.; Wang, L.; Gu, H.; Fan, C. DNA nanotechnology-enabled drug delivery systems. Chem. Rev. 2019, 119, 6459–6506. [Google Scholar] [CrossRef]
  138. Chen, Y.; Qin, D.; Zou, J.; Li, X.; Guo, X.D.; Tang, Y.; Liu, C.; Chen, W.; Kong, N.; Zhang, C.Y.; et al. Living leukocyte-based drug delivery systems. Adv. Mater. 2022. [Google Scholar] [CrossRef]
  139. Wong, P.T.; Choi, S.K. Mechanisms of drug release in nanotherapeutic delivery systems. Chem. Rev. 2015, 115, 3388–3432. [Google Scholar] [CrossRef]
  140. Guo, S.; Liang, T.; Song, Y.; Cheng, M.; Hu, X.-Y.; Zhu, J.-J.; Wang, L. Supramolecular polymersomes constructed from water-soluble pillar[5]arene and cationic poly(glutamamide)s and their applications in targeted anticancer drug delivery. Polym. Chem. 2017, 8, 5718–5725. [Google Scholar] [CrossRef]
  141. Park, J.; Kim, K.; Seo, M. Hyper-cross-linked polymers with controlled multiscale porosity via polymerization-induced microphase separation within high internal phase emulsion. Chem. Commun. 2018, 54, 7908–7911. [Google Scholar] [CrossRef] [PubMed]
  142. Evans, A.M.; Strauss, M.J.; Corcos, A.R.; Hirani, Z.; Ji, W.; Hamachi, L.S.; Aguilar-Enriquez, X.; Chavez, A.D.; Smith, B.J.; Dichtel, W.R. Two-dimensional polymers and polymerizations. Chem. Rev. 2022, 122, 442–564. [Google Scholar] [CrossRef]
  143. Huang, C.; Qian, X.; Yang, R. Thermal conductivity of polymers and polymer nanocomposites. Mater. Sci. Eng. R Rep. 2018, 132, 1–22. [Google Scholar] [CrossRef] [Green Version]
  144. Dong, S.; Zheng, B.; Wang, F.; Huang, F. Supramolecular polymers constructed from macrocycle-based host–guest molecular recognition motifs. Acc. Chem. Res. 2014, 47, 1982–1994. [Google Scholar] [CrossRef]
  145. Kuo, T.-C.; Hsueh, J.-C.; Chiou, C.-Y.; Su, C.-H.; Lee, J.-T. Ionically cross-linked polymers as asymmetric gel polymer electrolytes for enhanced cycle performance of lithium–sulfur batteries. ACS Macro Lett. 2021, 10, 110–115. [Google Scholar] [CrossRef]
  146. Scott, T.F.; Schneider, A.D.; Cook, W.D.; Bowman, C.N. Photoinduced plasticity in cross-linked polymers. Science 2005, 308, 1615–1617. [Google Scholar] [CrossRef]
  147. Wang, M.; Li, Q.; Li, E.; Liu, J.; Zhou, J.; Huang, F. Vapochromic behaviors of a solid-state supramolecular polymer based on exo-wall complexation of perethylated pillar[5]arene with 1,2,4,5-tetracyanobenzene. Angew. Chem. Int. Ed. 2021, 60, 8115–8120. [Google Scholar] [CrossRef] [PubMed]
  148. Li, Z.; Wu, S.; Lv, W.; Shao, J.-J.; Kang, F.; Yang, Q.-H. Graphene emerges as a versatile template for materials preparation. Small 2016, 12, 2674–2688. [Google Scholar] [CrossRef]
  149. Kobayashi, Y.; Honjo, K.; Kitagawa, S.; Uemura, T. Preparation of porous polysaccharides templated by coordination polymer with three-dimensional nanochannels. ACS Appl. Mater. Interfaces 2017, 9, 11373–11379. [Google Scholar] [CrossRef]
  150. Liu, Y.; Liao, Y.; Li, P.; Li, Z.T.; Ma, D. Cross-linked pillar[6]arene nanosponges fabricated by the use of a supra-amphiphilic template: Cargo encapsulation and overcoming multidrug resistance. ACS Appl. Mater. Interfaces 2020, 12, 7974–7983. [Google Scholar] [CrossRef]
  151. Yao, X.; Liu, J.; Yang, C.; Yang, X.; Wei, J.; Xia, Y.; Gong, X.; Suo, Z. Hydrogels: Hydrogel paint. Adv. Mater. 2019, 31, 1970276. [Google Scholar] [CrossRef]
  152. Yang, C.; Suo, Z. Hydrogel ionotronics. Nat. Rev. Mater. 2018, 3, 125–142. [Google Scholar] [CrossRef]
  153. Wang, Y. Programmable hydrogels. Biomaterials 2018, 178, 663–680. [Google Scholar] [CrossRef] [PubMed]
  154. Correa, S.; Grosskopf, A.K.; Lopez Hernandez, H.; Chan, D.; Yu, A.C.; Stapleton, L.M.; Appel, E.A. Translational applications of hydrogels. Chem. Rev. 2021, 121, 11385–11457. [Google Scholar] [CrossRef]
  155. Rojek, K.O.; Ćwiklińska, M.; Kuczak, J.; Guzowski, J. Microfluidic formulation of topological hydrogels for microtissue engineering. Chem. Rev. 2022, 122, 16839–16909. [Google Scholar] [CrossRef] [PubMed]
  156. Zhang, J.; Bo, S.; Wang, R.; Fang, J.; Wang, X.-G.; Bai, Y.; Ma, Z.; Liang, Y.; Zhang, M.; Yu, Q.; et al. Supramolecular polymer gel lubricant with excellent mechanical stability and tribological performances. ACS Appl. Mater. Interfaces 2022, 14, 45934–45944. [Google Scholar] [CrossRef]
  157. Yuan, D.; Xu, B. Heterotypic supramolecular hydrogels. J. Mater. Chem. B 2016, 4, 5638–5649. [Google Scholar] [CrossRef]
  158. Bhattacharya, S.; Samanta, S.K. Soft-nanocomposites of nanoparticles and nanocarbons with supramolecular and polymer gels and their applications. Chem. Rev. 2016, 116, 11967–12028. [Google Scholar] [CrossRef]
  159. Ni, M.; Zhang, N.; Xia, W.; Wu, X.; Yao, C.; Liu, X.; Hu, X.Y.; Lin, C.; Wang, L. Dramatically promoted swelling of a hydrogel by pillar[6]arene-ferrocene complexation with multistimuli responsiveness. J. Am. Chem. Soc. 2016, 138, 6643–6649. [Google Scholar] [CrossRef]
  160. Liu, Y.; Shi, B.; Wang, H.; Shangguan, L.; Li, Z.; Zhang, M.; Huang, F. Construction of metallacage-cored supramolecular gel by hierarchical self-assembly of metal coordination and pillar[5]arene-based host−guest recognition. Macromol. Rapid Commun. 2018, 39, e1800655. [Google Scholar] [CrossRef]
  161. Fu, S.; Zhang, Y.; Guan, S.; Huang, Q.; Wang, R.; Tian, R.; Zang, M.; Qiao, S.; Zhang, X.; Liu, S.; et al. Reductive-responsive, single-molecular-layer polymer nanocapsules prepared by lateral-functionalized pillar[5]arenes for targeting anticancer drug delivery. ACS Appl. Mater. Interfaces 2018, 10, 14281–14286. [Google Scholar] [CrossRef]
  162. Dutta, D.; Ke, W.; Xi, L.; Yin, W.; Zhou, M.; Ge, Z. Block copolymer prodrugs: Synthesis, self-assembly, and applications for cancer therapy. WIREs Nanomed. Nanobiotechnol. 2020, 12, e1585. [Google Scholar] [CrossRef]
  163. Yasen, W.; Dong, R.; Aini, A.; Zhu, X. Recent advances in supramolecular block copolymers for biomedical applications. J. Mater. Chem. B 2020, 8, 8219–8231. [Google Scholar] [CrossRef] [PubMed]
  164. Sarkar, A.; Sasmal, R.; Empereur-mot, C.; Bochicchio, D.; Kompella, S.V.K.; Sharma, K.; Dhiman, S.; Sundaram, B.; Agasti, S.S.; Pavan, G.M.; et al. Self-sorted, random, and block supramolecular copolymers via sequence controlled, multicomponent self-assembly. J. Am. Chem. Soc. 2020, 142, 7606–7617. [Google Scholar] [CrossRef] [PubMed]
  165. Jung, S.H.; Bochicchio, D.; Pavan, G.M.; Takeuchi, M.; Sugiyasu, K. A block supramolecular polymer and its kinetically enhanced stability. J. Am. Chem. Soc. 2018, 140, 10570–10577. [Google Scholar] [CrossRef] [PubMed]
  166. Yang, S.K.; Ambade, A.V.; Weck, M. Main-chain supramolecular block copolymers. Chem. Soc. Rev. 2011, 40, 129–137. [Google Scholar] [CrossRef] [PubMed]
  167. Zhang, D.; Lv, P.; Zhou, C.; Zhao, Y.; Liao, X.; Yang, B. Cyclodextrin-based delivery systems for cancer treatment. Mater. Sci. Eng. C 2019, 96, 872–886. [Google Scholar] [CrossRef]
  168. Basilotta, R.; Mannino, D.; Filippone, A.; Casili, G.; Prestifilippo, A.; Colarossi, L.; Raciti, G.; Esposito, E.; Campolo, M. Role of calixarene in chemotherapy delivery strategies. Molecules 2021, 26, 3963. [Google Scholar] [CrossRef]
  169. Guan, S.; Liang, R.; Li, C.; Wei, M. A supramolecular material for dual-modal imaging and targeted cancer therapy. Talanta 2017, 165, 297–303. [Google Scholar] [CrossRef]
  170. Nguyen, B.-N.T.; Thoburn, J.D.; Grommet, A.B.; Howe, D.J.; Ronson, T.K.; Ryan, H.P.; Bolliger, J.L.; Nitschke, J.R. Coordination cages selectively transport molecular cargoes across liquid membranes. J. Am. Chem. Soc. 2021, 143, 12175–12180. [Google Scholar] [CrossRef]
  171. Paunovska, K.; Loughrey, D.; Dahlman, J.E. Drug delivery systems for RNA therapeutics. Nat. Rev. Genet. 2022, 23, 265–280. [Google Scholar] [CrossRef] [PubMed]
  172. Yu, G.; Yu, W.; Shao, L.; Zhang, Z.; Chi, X.; Mao, Z.; Gao, C.; Huang, F. Fabrication of a targeted drug delivery system from a pillar[5]arene-based supramolecular diblock copolymeric amphiphile for effective cancer therapy. Adv. Funct. Mater. 2016, 26, 8999–9008. [Google Scholar] [CrossRef]
  173. Wu, J.; Xia, L.; Liu, Z.; Xu, Z.; Cao, H.; Zhang, W. Fabrication of a dual-stimuli-responsive supramolecular micelle from a pillar[5]arene-based supramolecular diblock copolymer for photodynamic therapy. Macromol. Rapid. Commun. 2019, 40, e1900240. [Google Scholar] [CrossRef] [PubMed]
  174. He, J.; Chen, J.; Lin, S.; Niu, D.; Hao, J.; Jia, X.; Li, N.; Gu, J.; Li, Y.; Shi, J. Synthesis of a pillar[5]arene-based polyrotaxane for enhancing the drug loading capacity of PCL-based supramolecular amphiphile as an excellent drug delivery platform. Biomacromolecules 2018, 19, 2923–2930. [Google Scholar] [CrossRef]
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Figure 1. General molecular structures and schematic illustration of pillar[n]arenes.
Figure 1. General molecular structures and schematic illustration of pillar[n]arenes.
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Figure 2. Schematic representation of the structure of BP5A and iodide BODIPY, and the schematic illustration of photo-induced generation of reactive oxygen species (I). Cell viability of HeLa cells at different concentrations of supramolecular polymer under normoxia or hypoxia conditions (II). Confocal laser scanning microscopy images of calcein AM/PI-stained HeLa cells (III). (reproduced with permission of Royal Society of Chemistry from ref. [106]).
Figure 2. Schematic representation of the structure of BP5A and iodide BODIPY, and the schematic illustration of photo-induced generation of reactive oxygen species (I). Cell viability of HeLa cells at different concentrations of supramolecular polymer under normoxia or hypoxia conditions (II). Confocal laser scanning microscopy images of calcein AM/PI-stained HeLa cells (III). (reproduced with permission of Royal Society of Chemistry from ref. [106]).
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Figure 3. Schematic illustration of FA-Py/SP/GOx/Dox NPs in targeted synergistic chemo–chemodynamic therapy (I). Body weight curves of tumor-bearing mice after different formulations (II). Tumor growth inhibition curves of tumor-bearing mice after different formulations (III). (reproduced with permission of Springer Nature from ref. [111]).
Figure 3. Schematic illustration of FA-Py/SP/GOx/Dox NPs in targeted synergistic chemo–chemodynamic therapy (I). Body weight curves of tumor-bearing mice after different formulations (II). Tumor growth inhibition curves of tumor-bearing mice after different formulations (III). (reproduced with permission of Springer Nature from ref. [111]).
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Figure 5. Schematic illustration of Q-P–A@CP[5]A in antibacterial and antitumor therapies (I). Tumor growth inhibition curves of HT29 tumor-bearing nude mice after various formulations (* p < 0.05) (II). Body weights of HT29 tumor-bearing nude mice after various formulations (III). (reproduced with permission of Royal Society of Chemistry from ref. [136]).
Figure 5. Schematic illustration of Q-P–A@CP[5]A in antibacterial and antitumor therapies (I). Tumor growth inhibition curves of HT29 tumor-bearing nude mice after various formulations (* p < 0.05) (II). Body weights of HT29 tumor-bearing nude mice after various formulations (III). (reproduced with permission of Royal Society of Chemistry from ref. [136]).
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Figure 6. Schematic illustration of supramolecular polymersomes in targeted drug delivery (I). In vitro cytotoxicities of free MTZ, MTZ-loaded nontargeting and targeting polymersomes against HeLa cells (II). In vitro cytotoxicities of unloaded nontargeting and targeting polymersomes against HeLa cells (* p < 0.05) (III). (reproduced with permission of American Chemical Society from ref. [140]).
Figure 6. Schematic illustration of supramolecular polymersomes in targeted drug delivery (I). In vitro cytotoxicities of free MTZ, MTZ-loaded nontargeting and targeting polymersomes against HeLa cells (II). In vitro cytotoxicities of unloaded nontargeting and targeting polymersomes against HeLa cells (* p < 0.05) (III). (reproduced with permission of American Chemical Society from ref. [140]).
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Figure 7. Schematic illustration of crosslinked pillar[6]arene nanosponges (NS) in overcoming MDR (I). Viability of HeLa cells treated with NS at different concentrations (II). IC50 plot curve of DOX and DOX-loaded NS against MCF-7/ADR cell line (III). (reproduced with permission of Royal Society of Chemistry from ref. [150]).
Figure 7. Schematic illustration of crosslinked pillar[6]arene nanosponges (NS) in overcoming MDR (I). Viability of HeLa cells treated with NS at different concentrations (II). IC50 plot curve of DOX and DOX-loaded NS against MCF-7/ADR cell line (III). (reproduced with permission of Royal Society of Chemistry from ref. [150]).
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Figure 8. Schematic illustration of pillar[5]arene-based single-molecular-layer polymer nanocapsules in targeting anticancer drug delivery (I). In vitro cytotoxicity of different vehicles against HepG2 cell (II). Quantitative uptake of DOX, DOX-nanocap, and RGD ligand-DOX-nanocap by zebrafish larval at different concentrations (III). (reproduced with permission of American Chemical Society from ref. [161]).
Figure 8. Schematic illustration of pillar[5]arene-based single-molecular-layer polymer nanocapsules in targeting anticancer drug delivery (I). In vitro cytotoxicity of different vehicles against HepG2 cell (II). Quantitative uptake of DOX, DOX-nanocap, and RGD ligand-DOX-nanocap by zebrafish larval at different concentrations (III). (reproduced with permission of American Chemical Society from ref. [161]).
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Figure 9. Schematic illustration of supramolecular polymersome in drug delivery (I). Tumor growth inhibition curves of HeLa tumor with different formulations (II). Body weight changes in mice bearing HeLa tumors after different treatments (III). (reproduced with permission of John Wiley and Sons from ref. [172]).
Figure 9. Schematic illustration of supramolecular polymersome in drug delivery (I). Tumor growth inhibition curves of HeLa tumor with different formulations (II). Body weight changes in mice bearing HeLa tumors after different treatments (III). (reproduced with permission of John Wiley and Sons from ref. [172]).
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Figure 10. Schematic illustration of dual-stimuli-responsive supramolecular nanoparticles from a pillar[5]arene-based supramolecular diblock copolymer for PDT (I). Drug release profiles of supramolecular nanocarriers (II). The dark cytotoxicity of free PhA and PhA-loaded nanocarriers against A549 cells (III). (reproduced with permission of John Wiley and Sons from ref. [173]).
Figure 10. Schematic illustration of dual-stimuli-responsive supramolecular nanoparticles from a pillar[5]arene-based supramolecular diblock copolymer for PDT (I). Drug release profiles of supramolecular nanocarriers (II). The dark cytotoxicity of free PhA and PhA-loaded nanocarriers against A549 cells (III). (reproduced with permission of John Wiley and Sons from ref. [173]).
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Yan, M.; Zhou, J. Pillararene-Based Supramolecular Polymers for Cancer Therapy. Molecules 2023, 28, 1470. https://doi.org/10.3390/molecules28031470

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Yan M, Zhou J. Pillararene-Based Supramolecular Polymers for Cancer Therapy. Molecules. 2023; 28(3):1470. https://doi.org/10.3390/molecules28031470

Chicago/Turabian Style

Yan, Miaomiao, and Jiong Zhou. 2023. "Pillararene-Based Supramolecular Polymers for Cancer Therapy" Molecules 28, no. 3: 1470. https://doi.org/10.3390/molecules28031470

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