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Application of Nanoscale Materials for Cancer Diagnostic and Therapy

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A special issue of Nanomaterials (ISSN 2079-4991). This special issue belongs to the section "Biology and Medicines".

Deadline for manuscript submissions: closed (31 December 2020) | Viewed by 55035

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Prof. Dr. Houria Boulaiz

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Biosanitary Institute of Granada (ibs.GRANADA), Universidad de Granada, Granada, Spain
Interests: nanomedicine; drug delivery; core-shell nanodevices; suicide gene therapy; cancer stem cells; cell death

Special Issue Information

Dear Colleagues,

Currently, the most commonly used treatments for cancer are surgery, radiotherapy and chemotherapy. All three methods could lead to normal tissue damage or incomplete eradication of the tumor. There has been significant interest in developing innovative strategies more targeted towards treating this pathology. Nanotechnology offers the means to i) guide the surgical resection of tumors; ii) target chemotherapies directly and selectively to cancerous cells; and iii) enhance the therapeutic efficacy of radiation-based and other current treatment modalities. The synthesis of materials at the nanoscale and their use as anticancer therapy is now increasingly directed towards providing function for the design of precise engineered systems. All this will benefit the patient who will suffer fewer side effects, and will have a higher survival rate with a higher quality of life.

Smart nanomaterials represent one of the most interesting classes of materials for use as therapeutic platforms, both in the diagnosis and treatment of neoplasms. Diagnostic methods are essential for the early detection of cancer to enable their prompt treatment, minimizing possible damage to the rest of the organism. Diagnostic tools such as nanobiosensors, lab-on-a-chip and imaging systems based on the use of nanoparticles offer higher sensitivity and assist the early detection of disease, offering a better prognosis and greater possibilities for successful treatment. Moreover, nanovehicles—nanoscale compounds used as a therapeutic tool and designed to specifically accumulate in the sites of the body where they are needed in order to improve pharmacotherapeutic outcomes—are one of the most important nanotechnology applications developed over the past decade. Diverse platforms of nanotechnology such as liposomes, micelles, core–shell nanodevices, hydrogels, and polymersomes can be utilized to develop more sophisticated, cancer-cell-targeted therapies and to combine different drugs into a single nanotherapeutic agent for synergistic therapeutic benefits.

Prof. Dr. Houria Boulaiz
Guest Editor

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Keywords

Nanobiosensors
Lab-on-a-Chip
Imaging systems
Drug delivery
Liposomes
Micelles
Core–Shell Nanodevices
Hydrogels

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Published Papers (11 papers)

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11 pages, 3236 KiB

Open AccessArticle

Polydopamine-Coated Laponite Nanoplatforms for Photoacoustic Imaging-Guided Chemo-Phototherapy of Breast Cancer

by Renna Liu, Fanli Xu, Lu Wang, Mengxue Liu, Xueyan Cao, Xiangyang Shi and Rui Guo

Nanomaterials 2021, 11(2), 394; https://doi.org/10.3390/nano11020394 - 4 Feb 2021

Cited by 21 | Viewed by 3403

Abstract

Theranostic nanoplatforms combining photosensitizers and anticancer drugs have aroused wide interest due to the real-time photoacoustic (PA) imaging capability and improved therapeutic efficacy by the synergistic effect of chemotherapy and phototherapy. In this study, polydopamine (PDA) coated laponite (LAP) nanoplatforms were synthesized to efficiently load indocyanine green (ICG) and doxorubicin (DOX), and modified with polyethylene glycol-arginine-glycine-aspartic acid (PEG-RGD) for PA imaging-guided chemo-phototherapy of cancer cells overexpressing α_vβ₃ integrin. The formed ICG/LAP-PDA-PEG-RGD/DOX nanoplatforms showed significantly higher photothermal conversion efficiency than ICG solution and excellent PA imaging capability, and could release DOX in a pH-sensitive and NIR laser-triggered way, which is highly desirable feature in precision chemotherapy. In addition, the ICG/LAP-PDA-PEG-RGD/DOX nanoplatforms could be uptake by cancer cells overexpressing α_vβ₃ integrin with high specificity, and thus serve as a targeted contrast agent for in vivo PA imaging of cancer. In vivo experiments with 4T1 tumor-bearing mouse model demonstrated that ICG/LAP-PDA-PEG-RGD/DOX nanoplatforms exhibited much stronger therapeutic effect and higher survival rate than monotherapy due to the synergetic chemo-phototherapy under NIR laser irradiation. Therefore, the reported ICG/LAP-PDA-PEG-RGD/DOX represents a promising theranostic nanoplatform for high effectiveness PA imaging-guided chemo-phototherapy of cancer cells overexpressing α_vβ₃ integrin. Full article

(This article belongs to the Special Issue Application of Nanoscale Materials for Cancer Diagnostic and Therapy)

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15 pages, 3728 KiB

Open AccessArticle

Solid Plasmonic Substrates for Breast Cancer Detection by Means of SERS Analysis of Blood Plasma

by Gabriela Fabiola Știufiuc, Valentin Toma, Mihail Buse, Radu Mărginean, Gabriela Morar-Bolba, Bogdan Culic, Romulus Tetean, Nicolae Leopold, Ioana Pavel, Constantin Mihai Lucaciu and Rareș Ionuț Știufiuc

Nanomaterials 2020, 10(6), 1212; https://doi.org/10.3390/nano10061212 - 21 Jun 2020

Cited by 27 | Viewed by 4029

Abstract

Surface enhanced Raman spectroscopy (SERS) represents a promising technique in providing specific molecular information that could have a major impact in biomedical applications, such as early cancer detection. SERS requires the presence of a suitable plasmonic substrate that can generate enhanced and reproducible diagnostic relevant spectra. In this paper, we propose a new approach for the synthesis of such a substrate, by using concentrated silver nanoparticles purified using the Tangential Flow Filtration method. The capacity of our substrates to generate reproducible and enhanced Raman signals, in a manner that can allow cancer detection by means of Multivariate Analysis (MVA) of Surface Enhanced Raman (SER) spectra, has been tested on blood plasma samples collected from 35 healthy donors and 29 breast cancer patients. All the spectra were analyzed by a combined Principal Component-Linear Discriminant Analysis. Our results facilitated the discrimination between healthy donors and breast cancer patients with 90% sensitivity, 89% specificity and 89% accuracy. This is a direct consequence of substrates’ ability to generate diagnostic relevant spectral information by performing SERS measurements on pristine blood plasma samples. Our results suggest that this type of solid substrate could be employed for the detection of other types of cancer or other diseases by means of MVA-SERS procedure. Full article

(This article belongs to the Special Issue Application of Nanoscale Materials for Cancer Diagnostic and Therapy)

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16 pages, 3169 KiB

Open AccessFeature PaperArticle

Superparamagnetic Iron Oxide Nanoparticles Modified with Silica Layers as Potential Agents for Lung Cancer Treatment

by Katarzyna Reczyńska, Marta Marszałek, Arkadiusz Zarzycki, Witold Reczyński, Kamil Kornaus, Elżbieta Pamuła and Wojciech Chrzanowski

Nanomaterials 2020, 10(6), 1076; https://doi.org/10.3390/nano10061076 - 31 May 2020

Cited by 64 | Viewed by 5534

Abstract

Superparamagnetic iron oxide nanoparticles (SPIONs) are promising drug delivery carriers and hyperthermia agents for the treatment of cancer. However, to ensure their safety in vivo, SPIONs must be modified in order to prevent unwanted iron release. Thus, SPIONs were coated with silica layers of different morphologies: non-porous (@SiO₂), mesoporous (@mSiO₂) or with a combination of non-porous and mesoporous layers (@SiO₂@mSiO₂) deposited via a sol–gel method. The presence of SiO₂ drastically changed the surface properties of the nanoparticles. The zeta potential changed from 19.6 ± 0.8 mV for SPIONs to −26.1 ± 0.1 mV for SPION@mSiO₂. The Brunauer–Emmett–Teller (BET) surface area increased from 7.54 ± 0.02 m²/g for SPIONs to 101.3 ± 2.8 m²/g for SPION@mSiO₂. All types of coatings significantly decreased iron release (at least 10 fold as compared to unmodified SPIONs). SPIONs and SPION@mSiO₂ were tested in vitro in contact with human lung epithelial cells (A549 and BEAS-2B). Both nanoparticle types were cytocompatible, although some delay in proliferation was observed for BEAS-2B cells as compared to A549 cells, which was correlated with increased cell velocity and nanoparticles uptake. Full article

(This article belongs to the Special Issue Application of Nanoscale Materials for Cancer Diagnostic and Therapy)

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11 pages, 1790 KiB

Open AccessCommunication

Tumor-Targeted Delivery of the p53-Activating Peptide VIP116 with PEG-Stabilized Lipodisks

by Sara Lundsten, Víctor Agmo Hernández, Lars Gedda, Tina Sarén, Christopher J. Brown, David P. Lane, Katarina Edwards and Marika Nestor

Nanomaterials 2020, 10(4), 783; https://doi.org/10.3390/nano10040783 - 19 Apr 2020

Cited by 16 | Viewed by 4149

Abstract

Stapled peptides targeting the interaction between p53 and its negative regulators MDM2 and MDM4 have exhibited great potential as anti-cancer drugs, albeit with room for improvement in formulation and tumor specificity. Lipid bilayer disks (lipodisks) have emerged as promising drug nanocarriers and can by attachment of targeting moieties be directed selectively towards tumor cells. Tumor-targeted delivery of stapled peptides by use of lipodisks may therefore increase the uptake in the tumors and limit toxicity in healthy tissue. Here, we utilized epidermal growth factor receptor (EGFR)-targeted lipodisks to deliver p53-activating stapled peptide VIP116 to EGFR-expressing tumor cells. We demonstrate that VIP116 can be stably formulated in lipodisks (maximum peptide/lipid molar ratio 0.11). In vitro cell studies verify specific binding of EGF-decorated lipodisks to tumor cells and confirm that targeted delivery of VIP116 significantly decreases tumor cell viability. Full article

(This article belongs to the Special Issue Application of Nanoscale Materials for Cancer Diagnostic and Therapy)

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21 pages, 4690 KiB

Open AccessArticle

Multifunctional, CD44v6-Targeted ORMOSIL Nanoparticles Enhance Drugs Toxicity in Cancer Cells

by Lucía Morillas-Becerril, Elektra Peta, Luca Gabrielli, Venera Russo, Elisa Lubian, Luca Nodari, Maria Grazia Ferlin, Paolo Scrimin, Giorgio Palù, Luisa Barzon, Ignazio Castagliuolo, Fabrizio Mancin and Marta Trevisan

Nanomaterials 2020, 10(2), 298; https://doi.org/10.3390/nano10020298 - 10 Feb 2020

Cited by 11 | Viewed by 3761

Abstract

Drug-loaded, PEGylated, organic-modified silica (ORMOSIL) nanoparticles prepared by microemulsion condensation of vinyltriethoxysilane (VTES) were investigated as potential nanovectors for cancer therapy. To target cancer stem cells, anti-CD44v6 antibody and hyaluronic acid (HA) were conjugated to amine-functionalized PEGylated ORMOSIL nanoparticles through thiol-maleimide and amide coupling chemistries, respectively. Specific binding and uptake of conjugated nanoparticles were studied on cells overexpressing the CD44v6 receptor. Cytotoxicity was subsequently evaluated in the same cells after the uptake of the nanoparticles. Internalization of nanocarriers loaded with the anticancer drug 3N-cyclopropylmethyl-7-phenyl-pyrrolo- quinolinone (MG2477) into cells resulted in a substantial increase of the cytotoxicity with respect to the free formulation. Targeting with anti-CD44v6 antibodies or HA yielded nanoparticles with similar effectiveness, in their optimized formulation. Full article

(This article belongs to the Special Issue Application of Nanoscale Materials for Cancer Diagnostic and Therapy)

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18 pages, 2890 KiB

Open AccessArticle

The Self-Adaptation Ability of Zinc Oxide Nanoparticles Enables Reliable Cancer Treatments

by Zane Taylor and Marcelo Marucho

Nanomaterials 2020, 10(2), 269; https://doi.org/10.3390/nano10020269 - 5 Feb 2020

Cited by 12 | Viewed by 3273

Abstract

Optimal procedures for reliable anti-cancer treatments involve the systematic delivery of zinc oxide nanoparticles, which spread through the circulatory system. The success of these procedures may largely depend on the NPs’ ability of self-adapting their physicochemical properties to overcome the different challenges facing at each stage on its way to the interior of a cancerous cell. In this article, we combine a multiscale approach, a unique nanoparticle model, and available experimental data to characterize the behavior of zinc oxide nanoparticles under different vessels rheology, pH levels, and biological environments. We investigate their ability to prevent aggregation, allow prolonged circulation time in the bloodstream, avoid clearance, conduct themselves through the capillarity system to reach damaged tissues, and selectively approach to target cancerous cells. Our results show that non-functionalized spherical zinc oxide nanoparticles with surface density N = 5.89 × 10⁻⁶ mol/m², protonation and deprotonation rates pKa = 10.9 and pKb = −5.5, and NP size in the range of 20–50 nm are the most effective, smart anti-cancer agents for biomedical treatments. Full article

(This article belongs to the Special Issue Application of Nanoscale Materials for Cancer Diagnostic and Therapy)

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19 pages, 5035 KiB

Open AccessArticle

Investigation of the Electrical Properties of Microtubule Ensembles under Cell-Like Conditions

by Aarat P. Kalra, Sahil D. Patel, Asadullah F. Bhuiyan, Jordane Preto, Kyle G. Scheuer, Usman Mohammed, John D. Lewis, Vahid Rezania, Karthik Shankar and Jack A. Tuszynski

Nanomaterials 2020, 10(2), 265; https://doi.org/10.3390/nano10020265 - 5 Feb 2020

Cited by 19 | Viewed by 5886

Abstract

Microtubules are hollow cylindrical polymers composed of the highly negatively-charged (~23e), high dipole moment (1750 D) protein α, β- tubulin. While the roles of microtubules in chromosomal segregation, macromolecular transport, and cell migration are relatively well-understood, studies on the electrical properties of microtubules have only recently gained strong interest. Here, we show that while microtubules at physiological concentrations increase solution capacitance, free tubulin has no appreciable effect. Further, we observed a decrease in electrical resistance of solution, with charge transport peaking between 20–60 Hz in the presence of microtubules, consistent with recent findings that microtubules exhibit electric oscillations at such low frequencies. We were able to quantify the capacitance and resistance of the microtubules (MT) network at physiological tubulin concentrations to be 1.27 × 10⁻⁵ F and 9.74 × 10⁴ Ω. Our results show that in addition to macromolecular transport, microtubules also act as charge storage devices through counterionic condensation across a broad frequency spectrum. We conclude with a hypothesis of an electrically tunable cytoskeleton where the dielectric properties of tubulin are polymerisation-state dependent. Full article

(This article belongs to the Special Issue Application of Nanoscale Materials for Cancer Diagnostic and Therapy)

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16 pages, 5574 KiB

Open AccessArticle

Eu-Doped Citrate-Coated Carbonated Apatite Luminescent Nanoprobes for Drug Delivery

by Ylenia Jabalera, Francesca Oltolina, Maria Prat, Concepcion Jimenez-Lopez, Jorge F. Fernández-Sánchez, Duane Choquesillo-Lazarte and Jaime Gómez-Morales

Nanomaterials 2020, 10(2), 199; https://doi.org/10.3390/nano10020199 - 23 Jan 2020

Cited by 11 | Viewed by 3568

Abstract

In the field of Nanomedicine, there is an increasing demand for new inorganic nanophosphors with low cytotoxicity and efficient loading-release ability of drugs for applications in bioimaging and drug delivery. This work assesses the potentiality of matured Eu-doped citrate-coated carbonated apatite nanoparticles to be used as theranostic platforms, for bioimaging, as luminescent nanoprobes, and for drug delivery applications, using Doxorubicin as a model drug. The drug adsorption isotherm fits the Langmuir–Freundlich (LF) model, showing that the Eu:cit-cAp nanoparticles can carry a maximum of 0.29 ± 0.02 mg Doxo mg Eu:cit-cAp⁻¹ (Q_max). The affinity constant K_FL for this binding is 44 ± 2 mL mg⁻¹, and the cooperativity coefficient r is 6 ± 1. The nanoparticle suspensions presented charge reversion from negative to positive after loading with Doxo as revealed by the ζ-potential versus pH characterization. The release of drug from the loaded nanoparticles was found to be strongly pH-dependent, being around 5 wt % at physiological pH 7.4 and 20 wt % at pH 5, in experiments lasting 24 h. Luminescence spectroscopic measurements of Doxo-loaded nanoparticles revealed the increase of luminescence with a decrease in the amount of adsorbed Doxo, due to the so-called inner filter effect. The nanoparticles free of Doxo were cytocompatible when interacted with two human cell lines derived respectively from a gastric carcinoma (GTL-16), and a hepatocarcinoma (Huh7), while Doxo-loaded nanoparticles displayed significant toxicity in a dose-dependent relationship. Therefore, the new nanoassemblies might have a dual function, as nanoprobes in bioimaging by detecting the fate of the nanoparticles in biological environments, and for monitoring the delivery of the drug in such environments, by measuring the rise of the luminescence provided by the desorption of Doxo. Full article

(This article belongs to the Special Issue Application of Nanoscale Materials for Cancer Diagnostic and Therapy)

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20 pages, 6752 KiB

Open AccessArticle

Synergistic Radiosensitization by Gold Nanoparticles and the Histone Deacetylase Inhibitor SAHA in 2D and 3D Cancer Cell Cultures

by Nóra Igaz, Krisztina Szőke, Dávid Kovács, Andrea Buhala, Zoltán Varga, Péter Bélteky, Zsolt Rázga, László Tiszlavicz, Csaba Vizler, Katalin Hideghéty, Zoltán Kónya and Mónika Kiricsi

Nanomaterials 2020, 10(1), 158; https://doi.org/10.3390/nano10010158 - 16 Jan 2020

Cited by 18 | Viewed by 4387

Abstract

Radiosensitizing agents are capable of augmenting the damage of ionizing radiation preferentially on cancer cells, thereby increasing the potency and the specificity of radiotherapy. Metal-based nanoparticles have recently gathered ground in radio-enhancement applications, owing to their exceptional competence in amplifying the cell-killing effects of irradiation. Our aim was to examine the radiosensitizing performance of gold nanoparticles (AuNPs) and the chromatin-modifying histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) alone and in combination. We observed that the colony-forming capability of cancer cells decreased significantly and the DNA damage, detected by γH2AX immunostaining, was substantially greater after combinational treatments than upon individual drug exposures followed by irradiation. Synergistic radiosensitizing effects of AuNPs and SAHA were proven on various cell lines, including radioresistant A549 and DU-145 cancer cells. 3D cultures often manifest radio- and drug-resistance, nevertheless, AuNPs in combination with SAHA could effectively enhance the potency of irradiation as the number of viable cells decreased significantly when spheroids received AuNP + SAHA prior to radiotherapy. Our results imply that a relaxed chromatin structure induced by SAHA renders the DNA of cancerous cells more susceptible to the damaging effects of irradiation-triggered, AuNP-released reactive electrons. This feature of AuNPs should be exploited in multimodal treatment approaches. Full article

(This article belongs to the Special Issue Application of Nanoscale Materials for Cancer Diagnostic and Therapy)

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Review

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25 pages, 5849 KiB

Open AccessReview

Nanotreatment and Nanodiagnosis of Prostate Cancer: Recent Updates

by Mahmood Barani, Fakhara Sabir, Abbas Rahdar, Rabia Arshad and George Z. Kyzas

Nanomaterials 2020, 10(9), 1696; https://doi.org/10.3390/nano10091696 - 28 Aug 2020

Cited by 75 | Viewed by 7829

Abstract

The fabrication and development of nanomaterials for the treatment of prostate cancer have gained significant appraisal in recent years. Advancements in synthesis of organic and inorganic nanomaterials with charge, particle size, specified geometry, ligand attachment etc have resulted in greater biocompatibility and active targeting at cancer site. Despite all of the advances made over the years in discovering drugs, methods, and new biomarkers for cancer of the prostate (PCa), PCa remains one of the most troubling cancers among people. Early on, effective diagnosis is an essential part of treating prostate cancer. Prostate-specific antigen (PSA) or serum prostate-specific antigen is the best serum marker widely accessible for diagnosis of PCa. Numerous efforts have been made over the past decade to design new biosensor-based strategies for biomolecules detection and PSA miniaturization biomarkers. The growing nanotechnology is expected to have a significant effect in the immediate future on scientific research and healthcare. Nanotechnology is thus predicted to find a way to solve one of the most and long-standing problem, “early cancer detection”. For early diagnosis of PCa biomarkers, different nanoparticles with different approaches have been used. In this review, we provide a brief description of the latest achievements and advances in the use of nanoparticles for PCa biomarker diagnosis. Full article

(This article belongs to the Special Issue Application of Nanoscale Materials for Cancer Diagnostic and Therapy)

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24 pages, 5099 KiB

Open AccessReview

Biomarkers-based Biosensing and Bioimaging with Graphene for Cancer Diagnosis

by Hui Gu, Huiling Tang, Ping Xiong and Zhihua Zhou

Nanomaterials 2019, 9(1), 130; https://doi.org/10.3390/nano9010130 - 21 Jan 2019

Cited by 56 | Viewed by 8204

Abstract

At the onset of cancer, specific biomarkers get elevated or modified in body fluids or tissues. Early diagnosis of these biomarkers can greatly improve the survival rate or facilitate effective treatment with different modalities. Potential nanomaterial-based biosensing and bioimaging are the main techniques in nanodiagnostics because of their ultra-high selectivity and sensitivity. Emerging graphene, including two dimensional (2D) graphene films, three dimensional (3D) graphene architectures and graphene hybrids (GHs) nanostructures, are attracting increasing interests in the field of biosensing and bioimaging. Due to their remarkable optical, electronic, and thermal properties; chemical and mechanical stability; large surface area; and good biocompatibility, graphene-based nanomaterials are applicable alternatives as versatile platforms to detect biomarkers at the early stage of cancer. Moreover, currently, extensive applications of graphene-based biosensing and bioimaging has resulted in promising prospects in cancer diagnosis. We also hope this review will provide critical insights to inspire more exciting researches to address the current remaining problems in this field. Full article

(This article belongs to the Special Issue Application of Nanoscale Materials for Cancer Diagnostic and Therapy)

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