Nanoparticles for Cancer Therapy

A special issue of Biomolecules (ISSN 2218-273X).

Deadline for manuscript submissions: closed (31 May 2019) | Viewed by 47737

Special Issue Editor


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Guest Editor
1. Nuffield Department of Women’s and Reproductive Health, Oxford University, John Radcliffe Hospital, Headington, Oxford OX3 9DU, UK
2. Department of Engineering Science, Oxford University, Parks Road, Oxford OX1 3PJ, UK
Interests: nanoparticles; cancer therapy; cancer imaging; drug delivery
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Special Issue Information

Dear Colleagues,

Cancer still remains one of the main causes of death in the Western world. New and innovative ways to tackle the disease are needed. Nanoparticle technology has the potential to provide such an opportunity due to the molecular scale and unique properties of nancoscale materials. Nanoparticles can be used to carry chemotherapeutics, peptides, nucleotides; may carry imaging agents; or have intrinsic properties such as radiosensitization. Furthermore, multimodal particles may be able to combine all of these properties to effect localization, monitoring and therapy all from one construct. This Special Issue will highlight the most novel and promising developments in the field.

Dr. Helen Townley
Guest Editor

Manuscript Submission Information

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Keywords

  • Oncology
  • Cancer
  • Nanoparticle
  • delivery
  • release
  • therapy
  • multimodal
  • targetted
  • controlled
  • drug
  • chemotherapeutic
  • radiosensitizer
  • EPR
  • RNAi
  • Peptide
  • encapsulation.

Published Papers (10 papers)

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Editorial

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3 pages, 180 KiB  
Editorial
Nanoparticles as Vectors to Tackle Cancer
by Chengchen Duan and Helen E Townley
Biomolecules 2021, 11(11), 1729; https://doi.org/10.3390/biom11111729 - 19 Nov 2021
Cited by 4 | Viewed by 1683
Abstract
The aim of this Special Issue, “Nanoparticles for cancer therapy”, was to offer readers a comprehensive and up-to-date insight into the various applications of nanoparticles in cancer treatments [...] Full article
(This article belongs to the Special Issue Nanoparticles for Cancer Therapy)

Research

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13 pages, 1938 KiB  
Article
Monte Carlo Simulations of Heat Deposition during Photothermal Skin Cancer Therapy Using Nanoparticles
by J. Charles G. Jeynes, Freddy Wordingham, Laura J. Moran, Alison Curnow and Tim J. Harries
Biomolecules 2019, 9(8), 343; https://doi.org/10.3390/biom9080343 - 5 Aug 2019
Cited by 16 | Viewed by 5654
Abstract
Photothermal therapy using nanoparticles is a promising new approach for the treatment of cancer. The principle is to utilise plasmonic nanoparticle light interaction for efficient heat conversion. However, there are many hurdles to overcome before it can be accepted in clinical practice. One [...] Read more.
Photothermal therapy using nanoparticles is a promising new approach for the treatment of cancer. The principle is to utilise plasmonic nanoparticle light interaction for efficient heat conversion. However, there are many hurdles to overcome before it can be accepted in clinical practice. One issue is a current poor characterization of the thermal dose that is distributed over the tumour region and the surrounding normal tissue. Here, we use Monte Carlo simulations of photon radiative transfer through tissue and subsequent heat diffusion calculations, to model the spatial thermal dose in a skin cancer model. We validate our heat rise simulations against experimental data from the literature and estimate the concentration of nanorods in the tumor that are associated with the heat rise. We use the cumulative equivalent minutes at 43 °C (CEM43) metric to analyse the percentage cell kill across the tumour and the surrounding normal tissue. Overall, we show that computer simulations of photothermal therapy are an invaluable tool to fully characterize thermal dose within tumour and normal tissue. Full article
(This article belongs to the Special Issue Nanoparticles for Cancer Therapy)
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12 pages, 1828 KiB  
Article
Combinatorial Use of Chitosan Nanoparticles, Reversine, and Ionising Radiation on Breast Cancer Cells Associated with Mitosis Deregulation
by Sofia Piña Olmos, Roberto Díaz Torres, Eman Elbakrawy, Louise Hughes, Joseph Mckenna, Mark A. Hill, Munira Kadhim, Patricia Ramírez Noguera and Victor M. Bolanos-Garcia
Biomolecules 2019, 9(5), 186; https://doi.org/10.3390/biom9050186 - 12 May 2019
Cited by 13 | Viewed by 3972
Abstract
Breast cancer is the most commonly occurring cancer in women worldwide and the second most common cancer overall. The development of new therapies to treat this devastating malignancy is needed urgently. Nanoparticles are one class of nanomaterial with multiple applications in medicine, ranging [...] Read more.
Breast cancer is the most commonly occurring cancer in women worldwide and the second most common cancer overall. The development of new therapies to treat this devastating malignancy is needed urgently. Nanoparticles are one class of nanomaterial with multiple applications in medicine, ranging from their use as drug delivery systems and the promotion of changes in cell morphology to the control of gene transcription. Nanoparticles made of the natural polymer chitosan are easy to produce, have a very low immunogenic profile, and diffuse easily into cells. One hallmark feature of cancer, including breast tumours, is the genome instability caused by defects in the spindle-assembly checkpoint (SAC), the molecular signalling mechanism that ensures the timely and high-fidelity transmission of the genetic material to an offspring. In recent years, the use of nanoparticles to treat cancer cells has gained momentum. This is in part because nanoparticles made of different materials can sensitise cancer cells to chemotherapy and radiotherapy. These advances prompted us to study the potential sensitising effect of chitosan-based nanoparticles on breast cancer cells treated with reversine, which is a small molecule inhibitor of Mps1 and Aurora B that induces premature exit from mitosis, aneuploidy, and cell death, before and after exposure of the cancer cells to X-ray irradiation. Our measurements of metabolic activity as an indicator of cell viability, DNA damage by alkaline comet assay, and immunofluorescence using anti-P-H3 as a mitotic biomarker indicate that chitosan nanoparticles elicit cellular responses that affect mitosis and cell viability and can sensitise breast cancer cells to X-ray radiation (2Gy). We also show that such a sensitisation effect is not caused by direct damage to the DNA by the nanoparticles. Taken together, our data indicates that chitosan nanoparticles have potential application for the treatment of breast cancer as adjunct to radiotherapy. Full article
(This article belongs to the Special Issue Nanoparticles for Cancer Therapy)
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18 pages, 2720 KiB  
Article
Targeted Delivery of Nanoparticulate Cytochrome C into Glioma Cells Through the Proton-Coupled Folate Transporter
by Yuriy V. Kucheryavykh, Josue Davila, Jescelica Ortiz-Rivera, Mikhael Inyushin, Luis Almodovar, Miguel Mayol, Moraima Morales-Cruz, Alejandra Cruz-Montañez, Vanessa Barcelo-Bovea, Kai Griebenow and Lilia Y. Kucheryavykh
Biomolecules 2019, 9(4), 154; https://doi.org/10.3390/biom9040154 - 18 Apr 2019
Cited by 15 | Viewed by 4567
Abstract
In this study, we identified the proton-coupled folate transporter (PCFT) as a route for targeted delivery of drugs to some gliomas. Using the techniques of confocal imaging, quantitative reverse transcription-polymerase chain reaction (qRT-PCR), and small interfering (siRNA) knockdown against the PCFT, we demonstrated [...] Read more.
In this study, we identified the proton-coupled folate transporter (PCFT) as a route for targeted delivery of drugs to some gliomas. Using the techniques of confocal imaging, quantitative reverse transcription-polymerase chain reaction (qRT-PCR), and small interfering (siRNA) knockdown against the PCFT, we demonstrated that Gl261 and A172 glioma cells, but not U87 and primary cultured astrocytes, express the PCFT, which provides selective internalization of folic acid (FA)-conjugated cytochrome c-containing nanoparticles (FA-Cyt c NPs), followed by cell death. The FA-Cyt c NPs (100 µg/mL), had no cytotoxic effects in astrocytes but caused death in glioma cells, according to their level of expression of PCFT. Whole-cell patch clamp recording revealed FA-induced membrane currents in FA-Cyt c NPs-sensitive gliomas, that were reduced by siRNA PCFT knockdown in a similar manner as by application of FA-Cyt c NPs, indicating that the PCFT is a route for internalization of FA-conjugated NPs in these glioma cells. Analysis of human glioblastoma specimens revealed that at least 25% of glioblastomas express elevated level of either PCFT or folate receptor (FOLR1). We conclude that the PCFT provides a mechanism for targeted delivery of drugs to some gliomas as a starting point for the development of efficient methods for treating gliomas with high expression of PCFT and/or FOLR1. Full article
(This article belongs to the Special Issue Nanoparticles for Cancer Therapy)
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20 pages, 3208 KiB  
Article
Toxicity Mechanism of Low Doses of NaGdF4:Yb3+,Er3+ Upconverting Nanoparticles in Activated Macrophage Cell Lines
by Edyta Wysokińska, Jakub Cichos, Agnieszka Kowalczyk, Mirosław Karbowiak, Leon Strządała, Artur Bednarkiewicz and Wojciech Kałas
Biomolecules 2019, 9(1), 14; https://doi.org/10.3390/biom9010014 - 3 Jan 2019
Cited by 25 | Viewed by 4087
Abstract
Gadolinium-doped nanoparticles (NPs) are regarded as promising luminescent probes. In this report, we studied details of toxicity mechanism of low doses of NaGdF4-based fluorescent nanoparticles in activated RAW264.7, J774A.1 macrophages. These cell lines were specifically sensitive to the treatment with nanoparticles. [...] Read more.
Gadolinium-doped nanoparticles (NPs) are regarded as promising luminescent probes. In this report, we studied details of toxicity mechanism of low doses of NaGdF4-based fluorescent nanoparticles in activated RAW264.7, J774A.1 macrophages. These cell lines were specifically sensitive to the treatment with nanoparticles. Using nanoparticles of three different sizes, but with a uniform zeta potential (about −11 mV), we observed rapid uptake of NPs by the cells, resulting in the increased lysosomal compartment and subsequent superoxide induction along with a decrease in mitochondrial potential, indicating the impairment of mitochondrial homeostasis. At the molecular level, this led to upregulation of proapoptotic Bax and downregulation of anti-apoptotic Bcl-2, which triggered the apoptosis with phosphatidylserine externalization, caspase-3 activation and DNA fragmentation. We provide a time frame of the toxicity process by presenting data from different time points. These effects were present regardless of the size of nanoparticles. Moreover, despite the stability of NaGdF4 nanoparticles at low pH, we identified cell acidification as an essential prerequisite of cytotoxic reaction using acidification inhibitors (NH4Cl or Bafilomycin A1). Therefore, approaching the evaluation of the biocompatibility of such materials, one should keep in mind that toxicity could be revealed only in specific cells. On the other hand, designing gadolinium-doped NPs with increased resistance to harsh conditions of activated macrophage phagolysosomes should prevent NP decomposition, concurrent gadolinium release, and thus the elimination of its toxicity. Full article
(This article belongs to the Special Issue Nanoparticles for Cancer Therapy)
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21 pages, 6302 KiB  
Article
pH-Sensitive Co-Adsorption/Release of Doxorubicin and Paclitaxel by Carbon Nanotube, Fullerene, and Graphene Oxide in Combination with N-isopropylacrylamide: A Molecular Dynamics Study
by Milad Rezaian, Reza Maleki, Mohammad Dahri Dahroud, Abdolmohammad Alamdari and Milad Alimohammadi
Biomolecules 2018, 8(4), 127; https://doi.org/10.3390/biom8040127 - 29 Oct 2018
Cited by 43 | Viewed by 5095
Abstract
Nanotechnology based drug delivery systems for cancer therapy have been the topic of interest for many researchers and scientists. In this research, we have studied the pH sensitive co-adsorption and release of doxorubicin (DOX) and paclitaxel (PAX) by carbon nanotube (CNT), fullerene, and [...] Read more.
Nanotechnology based drug delivery systems for cancer therapy have been the topic of interest for many researchers and scientists. In this research, we have studied the pH sensitive co-adsorption and release of doxorubicin (DOX) and paclitaxel (PAX) by carbon nanotube (CNT), fullerene, and graphene oxide (GO) in combination with N-isopropylacrylamide (PIN). This simulation study has been performed by use of molecular dynamics. Interaction energies, hydrogen bond, and gyration radius were investigated. Results reveal that, compared with fullerene and GO, CNT is a better carrier for the co-adsorption and co-release of DOX and PAX. It can adsorb the drugs in plasma pH and release it in vicinity of cancerous tissues which have acidic pH. Investigating the number of hydrogen bonds revealed that PIN created many hydrogen bonds with water resulting in high hydrophilicity of PIN, hence making it more stable in the bloodstream while preventing from its accumulation. It is also concluded from this study that CNT and PIN would make a suitable combination for the delivery of DOX and PAX, because PIN makes abundant hydrogen bonds and CNT makes stable interactions with these drugs. Full article
(This article belongs to the Special Issue Nanoparticles for Cancer Therapy)
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13 pages, 2624 KiB  
Article
α-Tocopheryl Succinate-Based Polymeric Nanoparticles for the Treatment of Head and Neck Squamous Cell Carcinoma
by Carolina Sánchez-Rodríguez, Raquel Palao-Suay, Laura Rodrigáñez, María Rosa Aguilar, Sergio Martín-Saldaña, Julio San Román and Ricardo Sanz-Fernández
Biomolecules 2018, 8(3), 97; https://doi.org/10.3390/biom8030097 - 19 Sep 2018
Cited by 16 | Viewed by 4226
Abstract
The aim of this work is to study, in an in vitro head and neck squamous cell carcinomas model the anti-angiogenic and anti-migratory properties of self-assembled polymeric nanoparticles (NPs) with demonstrated selective anticancer activity. The NPs are based on α-tocopheryl succinate (α-TOS) encapsulated [...] Read more.
The aim of this work is to study, in an in vitro head and neck squamous cell carcinomas model the anti-angiogenic and anti-migratory properties of self-assembled polymeric nanoparticles (NPs) with demonstrated selective anticancer activity. The NPs are based on α-tocopheryl succinate (α-TOS) encapsulated in the hydrophobic core of the NPs. We analyzed the effect of the newly synthetized α-TOS-loaded NPs in proliferating endothelial cells and hypopharynx carcinoma squamous cells and measured markers of angiogenesis, apoptosis and reactive oxygen species (ROS). α-TOS-loaded NPs suppressed angiogenesis by inducing accumulation of ROS and inducing apoptosis of proliferating endothelial cells. These NPs also decrease the number and quality of capillary-like tubes in an in vitro three-dimensional (3D) experiment, decrease the production of the pro-angiogenic vascular endothelial growth factor and down-regulate the expression of its receptor. The anti-migratory efficacy of α-TOS is corroborated in hypopharynx carcinoma cells by decreasing the secretion of matrix metalloproteases 2 and 9 (MMP-2 and MMP-9) and inhibiting cell migration. These results confirm that α-TOS-based NPs not only present anticancer properties, but also antiangiogenic properties, therefore making them promising candidates for multi-active combinatorial anticancer therapy. Full article
(This article belongs to the Special Issue Nanoparticles for Cancer Therapy)
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Review

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23 pages, 2750 KiB  
Review
Albumin Nanovectors in Cancer Therapy and Imaging
by Alessandro Parodi, Jiaxing Miao, Surinder M. Soond, Magdalena Rudzińska and Andrey A. Zamyatnin
Biomolecules 2019, 9(6), 218; https://doi.org/10.3390/biom9060218 - 5 Jun 2019
Cited by 89 | Viewed by 8158
Abstract
Albumin nanovectors represent one of the most promising carriers recently generated because of the cost-effectiveness of their fabrication, biocompatibility, safety, and versatility in delivering hydrophilic and hydrophobic therapeutics and diagnostic agents. In this review, we describe and discuss the recent advances in how [...] Read more.
Albumin nanovectors represent one of the most promising carriers recently generated because of the cost-effectiveness of their fabrication, biocompatibility, safety, and versatility in delivering hydrophilic and hydrophobic therapeutics and diagnostic agents. In this review, we describe and discuss the recent advances in how this technology has been harnessed for drug delivery in cancer, evaluating the commonly used synthesis protocols and considering the key factors that determine the biological transport and the effectiveness of such technology. With this in mind, we highlight how clinical and experimental albumin-based delivery nanoplatforms may be designed for tackling tumor progression or improving the currently established diagnostic procedures. Full article
(This article belongs to the Special Issue Nanoparticles for Cancer Therapy)
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26 pages, 1958 KiB  
Review
Nanoparticle Activation Methods in Cancer Treatment
by Benjamin D White, Chengchen Duan and Helen E Townley
Biomolecules 2019, 9(5), 202; https://doi.org/10.3390/biom9050202 - 24 May 2019
Cited by 34 | Viewed by 4759
Abstract
In this review, we intend to highlight the progress which has been made in recent years around different types of smart activation nanosystems for cancer treatment. Conventional treatment methods, such as chemotherapy or radiotherapy, suffer from a lack of specific targeting and consequent [...] Read more.
In this review, we intend to highlight the progress which has been made in recent years around different types of smart activation nanosystems for cancer treatment. Conventional treatment methods, such as chemotherapy or radiotherapy, suffer from a lack of specific targeting and consequent off-target effects. This has led to the development of smart nanosystems which can effect specific regional and temporal activation. In this review, we will discuss the different methodologies which have been designed to permit activation at the tumour site. These can be divided into mechanisms which take advantage of the differences between healthy cells and cancer cells to trigger activation, and those which activate by a mechanism extrinsic to the cell or tumour environment. Full article
(This article belongs to the Special Issue Nanoparticles for Cancer Therapy)
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14 pages, 2227 KiB  
Review
The ROMP: A Powerful Approach to Synthesize Novel pH-Sensitive Nanoparticles for Tumor Therapy
by Philippe Bertrand, Christophe Blanquart and Valérie Héroguez
Biomolecules 2019, 9(2), 60; https://doi.org/10.3390/biom9020060 - 12 Feb 2019
Cited by 14 | Viewed by 3974
Abstract
Fast clearance, metabolism, and systemic toxicity are major limits for the clinical use of anti-cancer drugs. Histone deacetylase inhibitors (HDACi) present these defects, despite displaying promising anti-tumor properties on tumor cells in vitro and in in vivo models of cancer. The specific delivery [...] Read more.
Fast clearance, metabolism, and systemic toxicity are major limits for the clinical use of anti-cancer drugs. Histone deacetylase inhibitors (HDACi) present these defects, despite displaying promising anti-tumor properties on tumor cells in vitro and in in vivo models of cancer. The specific delivery of anti-cancer drugs into the tumor should improve their clinical benefit by limiting systemic toxicity and by increasing the anti-tumor effect. This paper deals with the synthesis of the polymeric nanoparticle platform, which was produced by Ring-Opening Metathesis Polymerization (ROMP), able to release anti-cancer drugs in dispersion, such as histone deacetylase inhibitors, into mesothelioma tumors. The core-shell nanoparticles (NPs) have stealth properties due to their poly(ethylene oxide) shell and can be viewed as universal nano-carriers on which any alkyne-modified anti-cancer molecule can be grafted by click chemistry. A cleavage reaction of the chemical bond between NPs and drugs through the contact of NPs with a medium presenting an acidic pH, which is typically a cancer tumor environment or an acidic intracellular compartment, induces a controlled release of the bioactive molecule in its native form. In our in vivo syngeneic model of mesothelioma, a highly selective accumulation of the particles in the tumor was obtained. The release of the drugs led to an 80% reduction of tumor weight for the best compound without toxicity. Our work demonstrates that the use of theranostic nanovectors leads to an optimized delivery of epigenetic inhibitors in tumors, which improves their anti-tumor properties in vivo. Full article
(This article belongs to the Special Issue Nanoparticles for Cancer Therapy)
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