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WIREs Nanomed Nanobiotechnol
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Mechanisms of nanoparticle radiosensitization

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Abstract Metal‐based nanoparticles applied to potentiating the effects of radiotherapy have drawn significant attention from the research community and are now available clinically. By improving our mechanistic understanding, nanoparticles are likely to evolve to provide very significant improvements in radiotherapy outcomes with only incremental increase in cost. This review critically assesses the inconsistent observations surrounding physical, physicochemical, chemical and biological mechanisms of radiosensitization. In doing so, a number of needs are identified for continuing research and are highlighted. The large degree of variability from one nanoparticle to another emphasizes that it is a mistake to generalize nanoparticle radiosensitizer mechanisms. Nanoparticle formulations should be considered in an analogous way as pharmacological agents and as a broad class of therapeutic agents, needing to be considered with a high degree of individuality with respect to their interactions and ultimate impact on radiobiological response. In the same way that no universal anti‐cancer drug exists, it is unlikely that a single nanoparticle formulation will lead to the best therapeutic outcomes for all cancers. The high degree of complexity and variability in mechanistic action provides notable opportunities for nanoparticle formulations to be optimized for specific indications. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Nanotechnology Approaches to Biology > Nanoscale Systems in Biology
Average tumor volume after: (a) no treatment (triangles, n = 12); (b) gold only (diamonds, n = 4); (c) irradiation only (30 Gy, 250 kVp, circles, n = 11); (d) intravenous gold injection (1.35 g Au/kg) followed by irradiation (squares, n = 10). (Reprinted with permission from Hainfeld et al. (2004). Copyright 2004 IPEM. IOP Publishing
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A model of the surface of a cell nucleus with an intensity map of reactive oxygen species, enhanced by the presence of gold nanoparticles, interacting with the membrane transposed. The lighter spots indicate highly localized and heterogeneous damage can result. Courtesy of Dylan Peukert
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An incident X‐ray (green) is incident on a 20 nm diameter nanoparticle (yellow) which results in the ejection and multiple ionizing interactions of electrons (red tracks). (Reprinted with permission from Butterworth et al. (2012). Copyright 2012 The Royal Society of Chemistry
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Three‐dimensional magnetic resonance imaging reconstructions of brain metastases from various primary sites after intravenous injection of AGuIX nanoparticles. (Reprinted with permission from Lux et al. (2019). Copyright 2019
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