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      Gold Nanoparticles as a Potent Radiosensitizer: A Transdisciplinary Approach from Physics to Patient

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          Abstract

          Over the last decade, a growing interest in the improvement of radiation therapies has led to the development of gold-based nanomaterials as radiosensitizer. Although the radiosensitization effect was initially attributed to a dose enhancement mechanism, an increasing number of studies challenge this mechanistic hypothesis and evidence the importance of chemical and biological contributions. Despite extensive experimental validation, the debate regarding the mechanism(s) of gold nanoparticle radiosensitization is limiting its clinical translation. This article reviews the current state of knowledge by addressing how gold nanoparticles exert their radiosensitizing effects from a transdisciplinary perspective. We also discuss the current and future challenges to go towards a successful clinical translation of this promising therapeutic approach.

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          Cellular uptake of nanoparticles: journey inside the cell

          Cellular association and trafficking of nanoscale materials enables us to both understand and exploit context-dependent phenomena in various disease states, their pathogenesis, and potential therapeutic approaches. Nanoscale materials are increasingly found in consumer goods, electronics, and pharmaceuticals. While these particles interact with the body in myriad ways, their beneficial and/or deleterious effects ultimately arise from interactions at the cellular and subcellular level. Nanoparticles (NPs) can modulate cell fate, induce or prevent mutations, initiate cell–cell communication, and modulate cell structure in a manner dictated largely by phenomena at the nano–bio interface. Recent advances in chemical synthesis have yielded new nanoscale materials with precisely defined biochemical features, and emerging analytical techniques have shed light on nuanced and context-dependent nano-bio interactions within cells. In this review, we provide an objective and comprehensive account of our current understanding of the cellular uptake of NPs and the underlying parameters controlling the nano-cellular interactions, along with the available analytical techniques to follow and track these processes.
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            Mediating tumor targeting efficiency of nanoparticles through design.

            Here we systematically examined the effect of nanoparticle size (10-100 nm) and surface chemistry (i.e., poly(ethylene glycol)) on passive targeting of tumors in vivo. We found that the physical and chemical properties of the nanoparticles influenced their pharmacokinetic behavior, which ultimately determined their tumor accumulation capacity. Interestingly, the permeation of nanoparticles within the tumor is highly dependent on the overall size of the nanoparticle, where larger nanoparticles appear to stay near the vasculature while smaller nanoparticles rapidly diffuse throughout the tumor matrix. Our results provide design parameters for engineering nanoparticles for optimized tumor targeting of contrast agents and therapeutics.
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              Hard and soft acids and bases, HSAB, part 1: Fundamental principles

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                Author and article information

                Journal
                Cancers (Basel)
                Cancers (Basel)
                cancers
                Cancers
                MDPI
                2072-6694
                23 July 2020
                August 2020
                : 12
                : 8
                : 2021
                Affiliations
                [1 ]Research Center for the Physics of Matter and Radiation (PMR-LARN), Namur Research Institute For Life Sciences (NARILIS), University of Namur, Rue de Bruxelles 61, B-5000 Namur, Belgium; sebastien.penninckx@ 123456unamur.be (S.P.); anne-catherine.heuskin@ 123456unamur.be (A.-C.H.); stephane.lucas@ 123456unamur.be (S.L.)
                [2 ]Unité de Recherche en Biologie Cellulaire (URBC), Namur Research Institute For Life Sciences (NARILIS), University of Namur, Rue de Bruxelles 61, B-5000 Namur, Belgium
                Author notes
                Author information
                https://orcid.org/0000-0002-3016-778X
                https://orcid.org/0000-0002-9169-1294
                Article
                cancers-12-02021
                10.3390/cancers12082021
                7464732
                32718058
                df79847c-6b8d-4923-9b1d-e1637e5f9ed2
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 17 June 2020
                : 21 July 2020
                Categories
                Review

                gold nanoparticle,radiosensitizer,protontherapy,mechanism,oxidative stress,clinical translation,nanomedicine

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