Biomolecules

Editorial

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3 pages, 180 KiB

Open AccessEditorial

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 1872

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

Open AccessArticle

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 5975

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

Open AccessArticle

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 4178

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

Open AccessArticle

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 4815

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

Open AccessArticle

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 26 | Viewed by 4314

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

Open AccessArticle

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 5341

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

Open AccessArticle

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 17 | Viewed by 4459

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

Open AccessEditor’s ChoiceReview

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 95 | Viewed by 8694

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

Open AccessReview

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 35 | Viewed by 5029

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

Open AccessReview

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 15 | Viewed by 4156

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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