Development of Polymer-Assisted Nanoparticles and Nanogels for Cancer Therapy: An Update
Abstract
:1. Introduction
2. Types of Polymer-Based Nanoparticles and Nanogels
2.1. Formulation of Polymeric Nanoparticles and Nanogels
2.1.1. Core–Shell Nanoparticles
2.1.2. Dendrimer/Hyperbranched Polymer
2.1.3. Polymersome
2.1.4. Polyplex
2.1.5. Polymeric Micelles
2.1.6. Nanogels
2.2. Fabrication Strategies of Polymeric Nanoparticles
2.2.1. Emulsification
2.2.2. Nanoprecipitation
2.2.3. Electrospraying
2.2.4. Microfluidic Technology
2.2.5. Preparation of Nanogels
2.3. Types of Polymers for Polymeric Nanoparticles Formation
2.3.1. Natural Polymers
2.3.2. Synthetic Polymers
2.3.3. Peptide-Polymer Conjugates
3. Functionally Active Nanoparticles for Cancer Therapy
3.1. Specific Feature of Polymers for Cancer Therapy
3.2. Engineering Strategies of Nanogels for Cancer Therapy
3.3. Polymeric Nanomaterials Targeting Various Cancers
Nanoparticle | Polymer | Function of Polymer | Cancer Type | Year | Status | Reference |
---|---|---|---|---|---|---|
Magnetite nanoparticles | Magnetic nanoparticles, coated with antibodies | The coating of the magnetic nanoparticles consist of antibodies such as epithelial cell adhesion molecule (EpCAM) and CD52 as markers to attempt to remove tumor cells from the blood. | prostate, colon, lung or pancreatic cancer and lymphoma or leukemia | 2017–current | Recruiting | [147] |
Cetuximab nanoparticles | Ethylcellulose, decorated with somatostatin analogue | Release drug at only above pH 6.8. Holds Cetuximab at pH 1.5. | Colon Cancer | 2018–current | Recruiting | [148] |
Immuno-tethered lipoplex nanoparticle (ILN) biochip | Immuno-tethered lipoplex | To monitor treatment response and to detect relapse in patient. | B-cell lymphoma | 2018–current | Recruiting | [149] |
Gadolinium-chelated polysiloxane based nanoparticles | Gadolinium-chelated polysiloxane | Has great theronostic properties by radiosensitization and diagnosis by multimodal imaging. | Brain metastases | 2019–current | Recruiting | [150] |
Quantum dots nanoparticles | Cds/ZnS core–shell type quantum dots with carboxylic acid, decorated with veldoreotide | Using veldoreotide as a somatostatin analog to deliver anticancer drugs to target and for bioimaging of the cancer cells. | Breast Cancer | 2019–current | Recruiting | [151] |
PLGA nanoparticle | PLGA | PLGA nanoparticles are minimal in toxicity and is used for drug delivery for anti-tumor immune response. | New York Esophageal Squamous Cell Carcinoma-1 (NY-ESO-1) positive cancers | 2021–current | Recruiting | [152] |
Ultrasmall Superparamagentic Iron Oxide nanoparticles (USPION) | Ferrotran | To detect lymph node metastases of solid tumors with the assistance of MRI. | Pancreatic Cancer | 2017–2021 | Recruiting | [153] |
Superparamagentic Iron Oxide nanoparticles (SPION) | Iron Oxide | To trace delayed sentinel lymph node dissection. | Breast Cancer | 2020–current | Recruiting | [154] |
Superparamagentic Iron Oxide nanoparticles (SPION) | Iron Oxide | Increase the safety of liver after stereotactic body radiotherapy by assisting in the detection and the avoidance of high levels of radiation. | Hepatocellular carcinomas | 2020–current | Recruiting | [155] |
Hafnium Oxide-containing nanoparticles NBTXR3 | Hafnium Oxide | To target cancer cells for destruction through radiation therapy. | Pancreatic Cancer | 2020–current | Recruiting | [156] |
Hafnium Oxide-containing nanoparticles NBTXR3 | Hafnium Oxide | To improve sensitivity of tumor cells to radiation therapy. | Recurrent/Metastatic Head and Neck Squamous Cell Cancer | 2021–current | Recruiting | [158] |
Hafnium Oxide-containing nanoparticles NBTXR3 | Hafnium Oxide | Using NBTXR3 to improve the effectiveness of radiation therapy. | Head and Neck Squamous Cell Cancer | 2021–current | Recruiting | [157] |
Albumin-bound Rapamycin nanoparticle (Nab-rapamycin) | Albumin | Along with pazopanib hydrochloride, it may block cell growth enxymes which in turn halts the growth of tumor cells. | Advance Nonadipocytic Soft Tissue Sarcomas | 2019–current | Recruiting | [159] |
Albumin-bound rapamycin, temozolomide, and irinotecan nanoparticles | Albumin | To evaluate the drug response as a combinational therapy. | Solid Tumors | 2017–current | Recruiting | [160] |
Albumin-bound Rapamycin nanoparticles (Nab-Rapamycin) | Albumin | To evaluate the effect of Nab-rapamycin alone or in combination with various drugs in patients. | Glioma and Glioblastoma | 2018–current | Recruiting | [173] |
Paclitaxel Albumin-bound nanoparticles (Nab-Paclitaxel) | Paclitaxel Albumin-bound combining with gemcitabine, and cisplastin with high dose of Ascorbic Acid | To improve survival of paclitaxel albumin-bound nanoparticle with gemcitabine comparing to only gemcitabine. | Pancreatic cancer | 2017–current | Recruiting | [161] |
Albumin-bound Paclitaxel nanoparticle (Nab-paclitaxel) | Albumin | As combinational drug therapy with cisplastin and gemcitabine. | Pacreatic Adenocarcinoma | 2019–current | Recruiting | [162] |
Albumin-bound Paclitaxel nanoparticle (Nab-paclitaxel) | Albumin | Nab-paclitaxel is able to stop tumor growth by killing, arrest cell division, or by preventing it from metastasis. | Metastatic Pancreatic Cancer | 2020–current | Recruiting | [163] |
Albumin-bound Paclitaxel nanoparticle (Nab-paclitaxel) | Albumin | Nab-paclitaxel is able to stop tumor growth by killing, arrest cell division, or by preventing it from metastasis. | Metastatic Pancreatic Cancer | 2020–current | Recruiting | [164] |
Albumin-bound Paclitaxel nanoparticle (Nab-paclitaxel) | Albumin | As combinational drug therapy. | Pancreatic Cancer | 2020–current | Recruiting | [165] |
Albumin-bound Paclitaxel nanoparticle (Nab-paclitaxel) | Albumin | As combinational drug therapy. | Triple Negative Breat Cancer | 2018–current | Recruiting | [166] |
Albumin-bound Paclitaxel nanoparticle (Nab-paclitaxel) | Albumin | Nab-paclitaxel is able to stop tumor growth by killing, arrest cell division, or by preventing it from metastasis. | Triple Negative Breast Cancer | 2020–current | Recruiting | [174] |
Albumin-bound Paclitaxel nanoparticle (Nab-paclitaxel) | Albumin | Nab-paclitaxel is able to stop tumor growth by killing, arrest cell division, or by preventing it from metastasis. | Biliary Tract Cancer | 2018–current | Recruiting | [167] |
Albumin-bound Paclitaxel nanoparticle (Nab-paclitaxel) | Albumin | Combinining nab-paclitaxel, gemcitabine, and cisplastin to halt growth of tumor cells. | Liver Bile Duct Cancer | 2018–current | Recruiting | [168] |
Nab-paclitaxel/Rituximab-coated nanoparticle | Albumin | Combining Nab-paclitaxel to halt growth by killing or stopping the groth of tumor cells, while using rituximab may affec the growth and spreading of tumor cells. | Reccurent or refraxtory B-cell non-Hodgkin lymphoma | 2019–current | Recruiting | [169] |
Albumin-bound Paclitaxel nanoparticle (Nab-paclitaxel) | Albumin | To evaluate the drug response as a combinational therapy. | Non-squamous non-small cell lung cancer (NSCLS) | 2020–current | Recruiting | [170] |
Albumin-bound Paclitaxel nanoparticle (Nab-paclitaxel) | Albumin | As combinational drug therapy with cisplastin and capecitabine | Esophageal cancer | 2020–current | Recruiting | [171] |
Albumin-bound Paclitaxel nanoparticle (Nab-paclitaxel) | Albumin | As combinational drug therapy with cisplastin and sinitilimab. | Esophageal cancer | 2020–current | Recruiting | [172] |
4. Mechanism of Anticancer Action
4.1. Targeting
4.2. Cellular Uptake
4.3. Drug Release
5. Limitation and Challenges
6. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Nanoparticle | Polymer and Additives | Function of Polymer | Drug/Anticancer Compound | Cancer Type | Tested Model | Target Action | Year | Reference |
---|---|---|---|---|---|---|---|---|
Doxorubicin-IR780-PEG-PCL-SS NPs (DOX IR780-PEG-PCL-SS NPs) | PEG-PCL-SS | Drug delivery | Doxorubicin | Bladder Cancer | MB49 cells (Mouse, C57BL/Icrf-a’) | NIR laser-controlled drug release and imaging guidance for chemo-photothermal synergistic therapy reduce tumor size and inhibit growth | 2020 | [116] |
Albendazole-loaded polyurethane NPs (ABZ-polyurethane NPs) | Polyurethane | Compatible to ABZ, better drug delivery | Albendazole | Breast Cancer | MCF-7, MDA-MB-231 cells | Apoptosis, increase ABZ anticancer potency | 2020 | [135] |
Noscapine-loaded mPEG-PLGA NPs (NOS-mPEG-PLGA-NPs) | mPEG-PLGA | Anticancer effect of Noscapine improved when encapsulated in nanoparticles compared to free form | Noscapine | Breast Cancer | 4T1 cells, 4T1 in BALB/c | Antiangiogenic, apoptotic effects | 2020 | [117] |
mertansine (MRT) or cabazitaxel (CBZ) loaded TPC–CS NPs (MRT/CBZ-TPC-CS NPs) | Chitosan (CS) + tetraphenylchlorin (TPC) | Increase drug loading | Mertansine/Cabazitaxel | Breast Cancer | MDA-MB-231, MDA-MB-468 cells | MRT or CBZ had higher cytotoxic effect compared to free drug | 2020 | [130] |
A. absinthium extract loaded polymeric nanoparticles (NVA-AA) | NIPAAM-VP-AA | Drug delivery | Artemisia absinthium extract | Breast Cancer | MCF-7, MDA MB-231 cells | Induces cytotoxicity, inhibition of cellular proliferation, induction of apoptosis | 2020 | [136] |
Bortezomib (BTZ) loaded PNPs of HPLA-BT NPs | HPLA-BT | Drug delivery, higher drug load | Bortezomib | Breast Cancer | MCF-7 cells | Higher cytotoxic effects of DL (drug loaded) -HPLA-BT PNPs and significant anticancer activity | 2020 | [138] |
Anastrozole loaded PEGylated polymer–lipid hybrid nanoparticles (ANZ -PLNPs) | PEG and lipid | stable encapsulated system with a high percentage of entrapment efficiency | Anastrozole | Breast Cancer | MCF-7 cells | Induction of apoptosis | 2020 | [118] |
Estradiol-conjugated hypoxia-responsive polymeric nanoparticles encapsulating doxorubicin | PLA17000-PEG2000-Estradiol | targeted delivery into the hypoxic niches of estrogen-receptor-positive breast cancer microtumors | Doxorubicin | Breast Cancer | MCF7 cells | Higher cytotoxicity of targeted polymersomes in hypoxia compared to in normoxia | 2020 | [137] |
quercetin loaded chitosan nanoparticles (QCT-CS NPs) | Chitosan | Better drug delivery, enhanced encapsulation efficiency and sustained release property | Quercetin | Breast Cancer | MDA-MB-468 cells | Cytotoxicity, decrease tumor growth | 2018 | [131] |
Lung Cancer | A549 cells | |||||||
DOX-loaded PEGylated therapeutic nanosystem for pH-sensitive release | PEG | releasing the drug in a controlled manner at acidic pH, increasing efficacy compared to doxorubicin in solution | Doxorubicin | Breast Cancer | MDA-MB-231 cells | Better anti-tumor activity, inhibits cell proliferation | 2020 | [119] |
Lung Cancer | A549, H520 cells | |||||||
3A.1-loaded pH-sensitive chitosan nanoparticles | naphthyl-grafted succinyl chitosan (NSC), octyl-grafted succinyl chitosan (OSC), and benzyl-grafted succinyl chitosan (BSC) | delivering anticancer drugs to the targeted colon cancer sites | Andrographolide analog | Colon Cancer | HT-29 cells | significantly lower IC50 than free drug and promotes apoptosis | 2018 | [132] |
Linoleic acid conjugated SN38 (LA-SN38)-loaded NPs (EBNPs) | PEO-PBO diblock copolymer | EBNPs had high drug loading efficiency and entrapment efficiency for LA-SN38, release behaviour of EBNPs was slow and sustained | Linoleic acid conjugated SN38 | Colon Cancer | HCT-116, HT-29 cells | Growth inhibitory effects, EBNPs promotes the uptake in cancer cells. EBNPs had prolonged blood circulation time. | 2019 | [124] |
Cur-loaded phenylboronic acid-containing framboidal nanoparticles | PBAAM, PEGAM, MBAM | Improved chemical stability of Cur and sustained release under physiological conditions | Curcumin | Colon Cancer | HT-29 cells | Antiangiogenic, reduced tumor weight | 2019 | [139] |
Chondroitin sulphate functionalized campththecin-loaded polymeric nanoparticles (CS-CPT-NPs) | Chitosan | Targeted drug delivery | Campththecin | Colon Cancer | CT-26 cells (Mouse, BALB/c) | significantly improved the anti-colon cancer activities, promote apoptosis effects | 2019 | [133] |
Afatinib or miR- loaded polylactic-co-glycolic acid surrounded by PEG-lipids (shell modified with ligand R and pH-sensitive CPP H) nanoparticles (Afatinib or miR-loaded PLGA NPs) | PLGA | Protect Afatinib and miR, improve drug delivery | Afatinib/miR | Colon Cancer | Caco-2 cells | pH-responsive characteristics to increase the sensitivity of colon cancer cells to afatinib. | 2019 | [146] |
5-FU-Chrysin-loaded PLGA-PEG-PLGA nanoparticles (5FU-Chrysin-PLGA-PEG-PLGA NPs) | PLGA-PEG-PLGA | Improve the functional delivery efficacy of 5-FU and Chrysin in cancer | 5-FU, Chrysin | Colon Cancer | HT-29 cells | Apoptosis, growth inhibitory effects | 2020 | [120] |
Simvastatin (SV) chitosan nanoparticles co-crosslinked with tripolyphosphate and chondroitin sulfate (SVSChSNPs) | Chitosan co-crosslinked with tripolyphosphate and chondroitin sulfate | Control the release pattern of SV. Particle size and positive surface charge of NPs enhances the accumulation of SV in intracellular compartments. | Simvastatin | Hepatic Cancer | HepG2 cells | enhanced the cytotoxicity of SV against HepG2 cells owing to its enhanced cellular uptake. ChS improved oral bioavailability | 2020 | [134] |
Naringenin-loaded Hyaluronic acid (HA) decorated PCL NPs (NAR-HA@CH-PCL-NP) | PCL | Drug delivery | Naringenin | Lung cancer | A549 cells | Cytotoxic effect and active targeting of NAR-HA@CH-PCL-NP. Further treatment with NAR-HA@CH-PCL-NP was found effective in tumor growth inhibitory effect against urethane-induced lung cancer in rat | 2018 | [142] |
EGFR-targeted LPNs loaded with CDDP and DOX | EGF-PEG-DSPE | Target drug delivery, faster release of DOX from LPNs than CDDP. | Doxorubicin | Lung Cancer | A549 cells | Improved anticancer activity with lower toxicity. Drug-loaded LPNs improved cytotoxicity | 2019 | [125] |
platinum–curcumin complexes loaded into pH and redox dual-responsive nanoparticles (PteCUR@PSPPN) | mPEG-SS-PBAE-PLGA | control intracellular release, synergistic anticancer effects | Platinum–curcumin | Lung Cancer | A549 cells | Synergistic anticancer effects, enhanced anti-metastatic activity | 2019 | [140] |
sorafenib (SF)-loaded cationically-modified polymeric nanoparticles (NPs) | PLGA | aerosolization efficiency for pulmonary delivery | Sorafenib | Lung Cancer | A549 cells | enhanced cell migration inhibition, reduction in cell survival, inhibition in the formation of colonies | 2020 | [141] |
Uncaria tomentosa extract (UT)-PLGA & UTPCL | PCL and PLGA | Better drug delivery—UT-PLGA nanoparticles showed higher drug loading | Uncaria tomentosa extract | Prostate Cancer | LNCaP, DU145 cells | UT-PLGA showed higher cytotoxicity towards DU145 cells, UTPCL showed higher cytotoxicity against LNCaP cells | 2019 | [127] |
Gemcitabine (GEM) NPs conjugated with linoleic acid (GEM NPs) | Linoleic acid | high drug-load, controlled release, improved intracellular uptake | Gemcitabine | Thyroid Cancer | B-CPAP, FTC-133 cells | Enhanced cytotoxic activity, induces apoptosis | 2020 | [143] |
Ecoflex® NPs loaded with DTX (DTX-NPs) | PEG 6000 | Targeted drug delivery | Docetaxel | Ovarian Cancer | SKOV-3, MDA-468 cells | Increase antitumor efficacy, enhanced cellular uptake. | 2018 | [144] |
DOX-verapamil/MPEG-PLA nanoparticles (DOX-VER-MPEG-PLA) | MPEG-PLA | co-delivery system –efficiently coencapsulate verapamil and chemotherapeutic agents. | Doxorubicin, Verapamil | Ovarian Cancer | A2780, SKOV3 cells | Tumor suppression | 2018 | [121] |
Metformin-loaded PLGA-PEG nanoparticles (MET-PLGA-PEG NPs) | PLGA-PEG | Improve drug delivery | Metformin | Ovarian Cancer | SKOV3 cells | Increased nuclei fragmentation and amount of apoptotic cells induced by MET-NPs, enhance ani-cancer effects | 2018 | [122] |
Curcumin (Cur)- loaded Polymeric poly(lactic-co-glycolic acid) (PLGA) nanoparticles (Cur-PLGA NPs) | PLGA | Stabilize curcumin in the presence of light, improved serum stability compared to free curcumin | Curcumin | Ovarian Cancer | SKOV3 cells | Cytotoxic effects on tumor cells upon irradiation at a low intensity inhibit tumor growth | 2019 | [128] |
Nisin-loaded PLA-PEG-PLA nanoparticles | PLA-PEG-PLA | Better protection and sustained release for nisin | Nisin | Gastrointestinal Cancer | AGS, KYSE-30 cells | Higher cytotoxic effect in nisin-loaded NPs, increase cell growth reduction when comparing to free nisin | 2018 | [123] |
Hepatic Cancer | Hep-G2 cells | |||||||
Blood Cancer | K562 cells | |||||||
Benznidazoles (BNZ)-loaded cationic polymeric nanoparticles (NPs) (BNZ-SA-Chol-PMMA NPs) | cationic polymethyl-methacrylate (PMMA) NPs | Improves drug efficacy | Benznidazoles | Colon Cancer | HT-29 cells | BNZ-NPs improved anticancer effect | 2019 | [145] |
Cervical Cancer | HeLa cells | |||||||
Hepatic Cancer | Hep-G2 cells |
Advantages | Disadvantages/Limitations |
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Neerooa, B.N.H.M.; Ooi, L.-T.; Shameli, K.; Dahlan, N.A.; Islam, J.M.M.; Pushpamalar, J.; Teow, S.-Y. Development of Polymer-Assisted Nanoparticles and Nanogels for Cancer Therapy: An Update. Gels 2021, 7, 60. https://doi.org/10.3390/gels7020060
Neerooa BNHM, Ooi L-T, Shameli K, Dahlan NA, Islam JMM, Pushpamalar J, Teow S-Y. Development of Polymer-Assisted Nanoparticles and Nanogels for Cancer Therapy: An Update. Gels. 2021; 7(2):60. https://doi.org/10.3390/gels7020060
Chicago/Turabian StyleNeerooa, Bibi Noorheen Haleema Mooneerah, Li-Ting Ooi, Kamyar Shameli, Nuraina Anisa Dahlan, Jahid M. M. Islam, Janarthanan Pushpamalar, and Sin-Yeang Teow. 2021. "Development of Polymer-Assisted Nanoparticles and Nanogels for Cancer Therapy: An Update" Gels 7, no. 2: 60. https://doi.org/10.3390/gels7020060