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Nanoparticle-Based Radiosensitization

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Physical Chemistry and Chemical Physics".

Deadline for manuscript submissions: closed (31 January 2020) | Viewed by 61601

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Dr. Ivan Kempson

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Future Industries Institute, University of South Australia, Mawson Lakes, SA 5095, Australia
Interests: nanomedicine; bio-inorganic interactions; physical chemistry; nanoparticles; radiotherapy; trace-elements
Special Issues, Collections and Topics in MDPI journals

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Dear Colleagues,

Radiotherapies are highly effective and economical. For instance, in cancer treatment radiotherapy contributes about 40% of cures, yet accounts for less than 10% of cancer-treatment costs. The delivery of electromagnetic radiation and energetic particles has advanced tremendously due to technical, engineering, and physical accomplishments. However, many treatments now have limited scope for further improvements without advancing our basic understanding and exploitation or manipulation of the physical, chemical, and biologcal attributes associated with the morbidity in question.

In this regard, nanoparticles offer avenues for enhancing current therapies and the exploration of experimental therapies by preferentially sensitizing target-tissues. A wave of ideas and technologies is building, with a number entering clinical trials. This spans diverse concepts aimed at enhancing physcial, chemical, and biologcal mechanisms, as well as developing nanoparticles for targetted delivery, and controlled delivery and release of radiosensitizing agents (small molecules, biologicals, and nanoparticles themselves).

With emerging knowledge, the molecular-scale roles in radiosensitization are increasingly critical to undertsanding mechanisms and developing radiosensitizers to enhance the interaction of electromagnetic radiation and particle interactions with biology. This Special Issue of the International Journal of Molecular Sciences provides exciting insight into the state-of–the-art of radiosensitization with nanoparticle technologies.

Dr. Ivan Kempson
Guest Editor

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Keywords

Nanoparticles
Radiosensitizers
External beam radiotherapy
Photodynamic therapy
Brachytherapy
Targeted alpha/beta therapy
Particle therapy

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Related Special Issue

Nanoparticle-Based Radiosensitization 2.0 in International Journal of Molecular Sciences (6 articles)

Published Papers (12 papers)

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Editorial

Jump to: Research, Review

3 pages, 178 KiB

Open AccessEditorial

Nanoparticle-Based Radiosensitization

by Ivan Kempson

Int. J. Mol. Sci. 2020, 21(8), 2879; https://doi.org/10.3390/ijms21082879 - 20 Apr 2020

Cited by 6 | Viewed by 1915

Abstract

Radiotherapy is a highly multidisciplinary field with respect to its foundations of research and development, and in its clinical utility [...] Full article

(This article belongs to the Special Issue Nanoparticle-Based Radiosensitization)

Research

Jump to: Editorial, Review

20 pages, 20694 KiB

Open AccessArticle

A Facile One-Pot Synthesis of Versatile PEGylated Platinum Nanoflowers and Their Application in Radiation Therapy

by Xiaomin Yang, Daniela Salado-Leza, Erika Porcel, César R. González-Vargas, Farah Savina, Diana Dragoe, Hynd Remita and Sandrine Lacombe

Int. J. Mol. Sci. 2020, 21(5), 1619; https://doi.org/10.3390/ijms21051619 - 27 Feb 2020

Cited by 42 | Viewed by 4989

Abstract

Nanomedicine has stepped into the spotlight of radiation therapy over the last two decades. Nanoparticles (NPs), especially metallic NPs, can potentiate radiotherapy by specific accumulation into tumors, thus enhancing the efficacy while alleviating the toxicity of radiotherapy. Water radiolysis is a simple, fast and environmentally-friendly method to prepare highly controllable metallic nanoparticles in large scale. In this study, we used this method to prepare biocompatible PEGylated (with Poly(Ethylene Glycol) diamine) platinum nanoflowers (Pt NFs). These nanoagents provide unique surface chemistry, which allows functionalization with various molecules such as fluorescent markers, drugs or radionuclides. The Pt NFs were produced with a controlled aggregation of small Pt subunits through a combination of grafted polymers and radiation-induced polymer cross-linking. Confocal microscopy and fluorescence lifetime imaging microscopy revealed that Pt NFs were localized in the cytoplasm of cervical cancer cells (HeLa) but not in the nucleus. Clonogenic assays revealed that Pt NFs amplify the gamma rays induced killing of HeLa cells with a sensitizing enhancement ratio (SER) of 23%, thus making them promising candidates for future cancer radiation therapy. Furthermore, the efficiency of Pt NFs to induce nanoscopic biomolecular damage by interacting with gamma rays, was evaluated using plasmids as molecular probe. These findings show that the Pt NFs are efficient nano-radio-enhancers. Finally, these NFs could be used to improve not only the performances of radiation therapy treatments but also drug delivery and/or diagnosis when functionalized with various molecules. Full article

(This article belongs to the Special Issue Nanoparticle-Based Radiosensitization)

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18 pages, 4868 KiB

Open AccessArticle

A Novel Approach for Non-Invasive Lung Imaging and Targeting Lung Immune Cells

by Amlan Chakraborty, Simon G. Royce, Cordelia Selomulya and Magdalena Plebanski

Int. J. Mol. Sci. 2020, 21(5), 1613; https://doi.org/10.3390/ijms21051613 - 27 Feb 2020

Cited by 17 | Viewed by 3935

Abstract

Despite developments in pulmonary radiotherapy, radiation-induced lung toxicity remains a problem. More sensitive lung imaging able to increase the accuracy of diagnosis and radiotherapy may help reduce this problem. Super-paramagnetic iron oxide nanoparticles are used in imaging, but without further modification can cause unwanted toxicity and inflammation. Complex carbohydrate and polymer-based coatings have been used, but simpler compounds may provide additional benefits. Herein, we designed and generated super-paramagnetic iron oxide nanoparticles coated with the neutral natural dietary amino acid glycine (GSPIONs), to support non-invasive lung imaging and determined particle biodistribution, as well as understanding the impact of the interaction of these nanoparticles with lung immune cells. These GSPIONs were characterized to be crystalline, colloidally stable, with a size of 12 ± 5 nm and a hydrodynamic diameter of 84.19 ± 18 nm. Carbon, Hydrogen, Nitrogen (CHN) elemental analysis estimated approximately 20.2 × 10³ glycine molecules present per nanoparticle. We demonstrated that it is possible to determine the biodistribution of the GSPIONs in the lung using three-dimensional (3D) ultra-short echo time magnetic resonance imaging. The GSPIONs were found to be taken up selectively by alveolar macrophages and neutrophils in the lung. In addition, the GSPIONs did not cause changes to airway resistance or induce inflammatory cytokines. Alveolar macrophages and neutrophils are critical regulators of pulmonary inflammatory diseases, including allergies, infections, asthma and chronic obstructive pulmonary disease (COPD). Therefore, pulmonary Magnetic Resonance (MR) imaging and preferential targeting of these lung resident cells by our nanoparticles offer precise imaging tools, which can be utilized to develop precision targeted radiotherapy as well as diagnostic tools for lung cancer, thereby having the potential to reduce the pulmonary complications of radiation. Full article

(This article belongs to the Special Issue Nanoparticle-Based Radiosensitization)

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12 pages, 1772 KiB

Open AccessArticle

Megavoltage Radiosensitization of Gold Nanoparticles on a Glioblastoma Cancer Cell Line Using a Clinical Platform

by Farasat Kazmi, Katherine A. Vallis, Balamurugan A. Vellayappan, Aishwarya Bandla, Duan Yukun and Robert Carlisle

Int. J. Mol. Sci. 2020, 21(2), 429; https://doi.org/10.3390/ijms21020429 - 9 Jan 2020

Cited by 28 | Viewed by 4285

Abstract

Gold nanoparticles (GNPs) have demonstrated significant dose enhancement with kilovoltage (kV) X-rays; however, recent studies have shown inconsistent findings with megavoltage (MV) X-rays. We propose to evaluate the radiosensitization effect on U87 glioblastoma (GBM) cells in the presence of 42 nm GNPs and irradiated with a clinical 6 MV photon beam. Cytotoxicity and radiosensitization were measured using MTS and clonogenic cellular radiation sensitivity assays, respectively. The sensitization enhancement ratio was calculated for 2 Gy (SER_2Gy) with GNP (100 μg/mL). Dark field and MTS assays revealed high co-localization and good biocompatibility of the GNPs with GBM cells. A significant sensitization enhancement of 1.45 (p = 0.001) was observed with GNP 100 μg/mL. Similarly, at 6 Gy, there was significant difference in the survival fraction between the GBM alone group (mean (M) = 0.26, standard deviation (SD) = 0.008) and the GBM plus GNP group (M = 0.07, SD = 0.05, p = 0.03). GNPs enabled radiosensitization in U87 GBM cells at 2 Gy when irradiated using a clinical platform. In addition to the potential clinical utility of GNPs, these studies demonstrate the effectiveness of a robust and easy to standardize an in-vitro model that can be employed for future studies involving metal nanoparticle plus irradiation. Full article

(This article belongs to the Special Issue Nanoparticle-Based Radiosensitization)

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17 pages, 5510 KiB

Open AccessArticle

Fluorescent Radiosensitizing Gold Nanoparticles

by Gloria Jiménez Sánchez, Pauline Maury, Lenka Stefancikova, Océane Campion, Gautier Laurent, Alicia Chateau, Farhan Bouraleh Hoch, Frédéric Boschetti, Franck Denat, Sophie Pinel, Jérôme Devy, Erika Porcel, Sandrine Lacombe, Rana Bazzi and Stéphane Roux

Int. J. Mol. Sci. 2019, 20(18), 4618; https://doi.org/10.3390/ijms20184618 - 18 Sep 2019

Cited by 19 | Viewed by 3982

Abstract

Ultrasmall polyaminocarboxylate-coated gold nanoparticles (NPs), Au@DTDTPA and Au@TADOTAGA, that have been recently developed exhibit a promising potential for image-guided radiotherapy. In order to render the radiosensitizing effect of these gold nanoparticles even more efficient, the study of their localization in cells is required to better understand the relation between the radiosensitizing properties of the agents and their localization in cells and in tumors. To achieve this goal, post-functionalization of Au@DTDTPA nanoparticles by near-infrared (NIF) organic dyes (aminated derivative of cyanine 5, Cy5-NH₂) was performed. The immobilization of organic Cy5-NH₂ dyes onto the gold nanoparticles confers to these radiosensitizers fluorescence properties which can be exploited for monitoring their internalization in cancerous cells, for determining their localization in cells by fluorescence microscopy (a common and powerful imaging tool in biology), and for following up on their accumulation in tumors after intravenous injection. Full article

(This article belongs to the Special Issue Nanoparticle-Based Radiosensitization)

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14 pages, 3145 KiB

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Combined Effects of Gold Nanoparticles and Ionizing Radiation on Human Prostate and Lung Cancer Cell Migration

by Elham Shahhoseini, Bryce N. Feltis, Masao Nakayama, Terrence J. Piva, Dodie Pouniotis, Salem S. Alghamdi and Moshi Geso

Int. J. Mol. Sci. 2019, 20(18), 4488; https://doi.org/10.3390/ijms20184488 - 11 Sep 2019

Cited by 19 | Viewed by 3072

Abstract

The effect of 15 nm-sized gold nanoparticles (AuNPs) and/or ionizing radiation (IR) on the migration and adhesion of human prostate (DU145) and lung (A549) cancer cell lines was investigated. Cell migration was measured by observing the closing of a gap created by a pipette tip on cell monolayers grown in 6-well plates. The ratio of the gap areas at 0 h and 24 h were used to calculate the relative migration. The relative migration of cells irradiated with 5 Gy was found to be 89% and 86% for DU145 and A549 cells respectively. When the cells were treated with 1 mM AuNPs this fell to ~75% for both cell lines. However, when the cells were treated with both AuNPs and IR an additive effect was seen, as the relative migration rate fell to ~60%. Of interest was that when the cells were exposed to either 2 or 5 Gy IR, their ability to adhere to the surface of a polystyrene culture plate was significantly enhanced, unlike that seen for AuNPs. The delays in gap filling (cell migration) in cells treated with IR and/or AuNPs can be attributed to cellular changes which also may have altered cell motility. In addition, changes in the cytoskeleton of the cancer cells may have also affected adhesiveness and thus the cancer cell’s motility response to IR. Full article

(This article belongs to the Special Issue Nanoparticle-Based Radiosensitization)

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22 pages, 7149 KiB

Open AccessArticle

Gold Nanoparticle Enhanced Proton Therapy: Monte Carlo Modeling of Reactive Species’ Distributions Around a Gold Nanoparticle and the Effects of Nanoparticle Proximity and Clustering

by Dylan Peukert, Ivan Kempson, Michael Douglass and Eva Bezak

Int. J. Mol. Sci. 2019, 20(17), 4280; https://doi.org/10.3390/ijms20174280 - 1 Sep 2019

Cited by 26 | Viewed by 3838

Abstract

Gold nanoparticles (GNPs) are promising radiosensitizers with the potential to enhance radiotherapy. Experiments have shown GNP enhancement of proton therapy and indicated that chemical damage by reactive species plays a major role. Simulations of the distribution and yield of reactive species from 10 ps to 1 µs produced by a single GNP, two GNPs in proximity and a GNP cluster irradiated with a proton beam were performed using the Geant4 Monte Carlo toolkit. It was found that the reactive species distribution at 1 µs extended a few hundred nm from a GNP and that the largest enhancement occurred over 50 nm from the nanoparticle. Additionally, the yield for two GNPs in proximity and a GNP cluster was reduced by up to 17% and 60% respectively from increased absorption. The extended range of action from the diffusion of the reactive species may enable simulations to model GNP enhanced proton therapy. The high levels of absorption for a large GNP cluster suggest that smaller clusters and diffuse GNP distributions maximize the total radiolysis yield within a cell. However, this must be balanced against the high local yields near a cluster particularly if the cluster is located adjacent to a biological target. Full article

(This article belongs to the Special Issue Nanoparticle-Based Radiosensitization)

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Review

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18 pages, 2046 KiB

Open AccessReview

Novel Strategies for Nanoparticle-Based Radiosensitization in Glioblastoma

by Henry Ruiz-Garcia, Cristopher Ramirez-Loera, Timothy D. Malouff, Danushka S. Seneviratne, Joshua D. Palmer and Daniel M. Trifiletti

Int. J. Mol. Sci. 2021, 22(18), 9673; https://doi.org/10.3390/ijms22189673 - 7 Sep 2021

Cited by 18 | Viewed by 3963

Abstract

Radiotherapy (RT) is one of the cornerstones in the current treatment paradigm for glioblastoma (GBM). However, little has changed in the management of GBM since the establishment of the current protocol in 2005, and the prognosis remains grim. Radioresistance is one of the hallmarks for treatment failure, and different therapeutic strategies are aimed at overcoming it. Among these strategies, nanomedicine has advantages over conventional tumor therapeutics, including improvements in drug delivery and enhanced antitumor properties. Radiosensitizing strategies using nanoparticles (NP) are actively under study and hold promise to improve the treatment response. We aim to describe the basis of nanomedicine for GBM treatment, current evidence in radiosensitization efforts using nanoparticles, and novel strategies, such as preoperative radiation, that could be synergized with nanoradiosensitizers. Full article

(This article belongs to the Special Issue Nanoparticle-Based Radiosensitization)

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23 pages, 686 KiB

Open AccessReview

Chemical Mechanisms of Nanoparticle Radiosensitization and Radioprotection: A Review of Structure-Function Relationships Influencing Reactive Oxygen Species

by Douglas Howard, Sonia Sebastian, Quy Van-Chanh Le, Benjamin Thierry and Ivan Kempson

Int. J. Mol. Sci. 2020, 21(2), 579; https://doi.org/10.3390/ijms21020579 - 16 Jan 2020

Cited by 74 | Viewed by 7342

Abstract

Metal nanoparticles are of increasing interest with respect to radiosensitization. The physical mechanisms of dose enhancement from X-rays interacting with nanoparticles has been well described theoretically, however have been insufficient in adequately explaining radiobiological response. Further confounding experimental observations is examples of radioprotection. Consequently, other mechanisms have gained increasing attention, especially via enhanced production of reactive oxygen species (ROS) leading to chemical-based mechanisms. Despite the large number of variables differing between published studies, a consensus identifies ROS-related mechanisms as being of significant importance. Understanding the structure-function relationship in enhancing ROS generation will guide optimization of metal nanoparticle radiosensitisers with respect to maximizing oxidative damage to cancer cells. This review highlights the physico-chemical mechanisms involved in enhancing ROS, commonly used assays and experimental considerations, variables involved in enhancing ROS generation and damage to cells and identifies current gaps in the literature that deserve attention. ROS generation and the radiobiological effects are shown to be highly complex with respect to nanoparticle physico-chemical properties and their fate within cells. There are a number of potential biological targets impacted by enhancing, or scavenging, ROS which add significant complexity to directly linking specific nanoparticle properties to a macroscale radiobiological result. Full article

(This article belongs to the Special Issue Nanoparticle-Based Radiosensitization)

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22 pages, 2886 KiB

Open AccessReview

Delivery of Nanoparticle-Based Radiosensitizers for Radiotherapy Applications

by Francis Boateng and Wilfred Ngwa

Int. J. Mol. Sci. 2020, 21(1), 273; https://doi.org/10.3390/ijms21010273 - 31 Dec 2019

Cited by 81 | Viewed by 7946

Abstract

Nanoparticle-based radiosensitization of cancerous cells is evolving as a favorable modality for enhancing radiotherapeutic ratio, and as an effective tool for increasing the outcome of concomitant chemoradiotherapy. Nevertheless, delivery of sufficient concentrations of nanoparticles (NPs) or nanoparticle-based radiosensitizers (NBRs) to the targeted tumor without or with limited systemic side effects on healthy tissues/organs remains a challenge that many investigators continue to explore. With current systemic intravenous delivery of a drug, even targeted nanoparticles with great prospect of reaching targeted distant tumor sites, only a portion of the administered NPs/drug dosage can reach the tumor, despite the enhanced permeability and retention (EPR) effect. The rest of the targeted NPs/drug remain in systemic circulation, resulting in systemic toxicity, which can decrease the general health of patients. However, the dose from ionizing radiation is generally delivered across normal tissues to the tumor cells (especially external beam radiotherapy), which limits dose escalation, making radiotherapy (RT) somewhat unsafe for some diseased sites despite the emerging development in RT equipment and technologies. Since radiation cannot discriminate healthy tissue from diseased tissue, the radiation doses delivered across healthy tissues (even with nanoparticles delivered via systemic administration) are likely to increase injury to normal tissues by accelerating DNA damage, thereby creating free radicals that can result in secondary tumors. As a result, other delivery routes, such as inhalation of nanoparticles (for lung cancers), localized delivery via intratumoral injection, and implants loaded with nanoparticles for local radiosensitization, have been studied. Herein, we review the current NP delivery techniques; precise systemic delivery (injection/infusion and inhalation), and localized delivery (intratumoral injection and local implants) of NBRs/NPs. The current challenges, opportunities, and future prospects for delivery of nanoparticle-based radiosensitizers are also discussed. Full article

(This article belongs to the Special Issue Nanoparticle-Based Radiosensitization)

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29 pages, 1506 KiB

Open AccessReview

Extracellular Vesicles in Modifying the Effects of Ionizing Radiation

by Tünde Szatmári, Rita Hargitai, Géza Sáfrány and Katalin Lumniczky

Int. J. Mol. Sci. 2019, 20(22), 5527; https://doi.org/10.3390/ijms20225527 - 6 Nov 2019

Cited by 39 | Viewed by 5858

Abstract

Extracellular vesicles (EVs) are membrane-coated nanovesicles actively secreted by almost all cell types. EVs can travel long distances within the body, being finally taken up by the target cells, transferring information from one cell to another, thus influencing their behavior. The cargo of EVs comprises of nucleic acids, lipids, and proteins derived from the cell of origin, thereby it is cell-type specific; moreover, it differs between diseased and normal cells. Several studies have shown that EVs have a role in tumor formation and prognosis. It was also demonstrated that ionizing radiation can alter the cargo of EVs. EVs, in turn can modulate radiation responses and they play a role in radiation-induced bystander effects. Due to their biocompatibility and selective targeting, EVs are suitable nanocarrier candidates of drugs in various diseases, including cancer. Furthermore, the cargo of EVs can be engineered, and in this way they can be designed to carry certain genes or even drugs, similar to synthetic nanoparticles. In this review, we describe the biological characteristics of EVs, focusing on the recent efforts to use EVs as nanocarriers in oncology, the effects of EVs in radiation therapy, highlighting the possibilities to use EVs as nanocarriers to modulate radiation effects in clinical applications. Full article

(This article belongs to the Special Issue Nanoparticle-Based Radiosensitization)

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17 pages, 885 KiB

Open AccessReview

Review of Therapeutic Applications of Radiolabeled Functional Nanomaterials

by Jongho Jeon

Int. J. Mol. Sci. 2019, 20(9), 2323; https://doi.org/10.3390/ijms20092323 - 10 May 2019

Cited by 71 | Viewed by 9520

Abstract

In the last two decades, various nanomaterials have attracted increasing attention in medical science owing to their unique physical and chemical characteristics. Incorporating radionuclides into conventionally used nanomaterials can confer useful additional properties compared to the original material. Therefore, various radionuclides have been used to synthesize functional nanomaterials for biomedical applications. In particular, several α- or β-emitter-labeled organic and inorganic nanoparticles have been extensively investigated for efficient and targeted cancer treatment. This article reviews recent progress in cancer therapy using radiolabeled nanomaterials including inorganic, polymeric, and carbon-based materials and liposomes. We first provide an overview of radiolabeling methods for preparing anticancer agents that have been investigated recently in preclinical studies. Next, we discuss the therapeutic applications and effectiveness of α- or β-emitter-incorporated nanomaterials in animal models and the emerging possibilities of these nanomaterials in cancer therapy. Full article

(This article belongs to the Special Issue Nanoparticle-Based Radiosensitization)

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