Nanoparticles for targeted cancer radiotherapy
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Nanoparticles for targeted cancer radiotherapy Roger M. Pallares1 and Rebecca J. Abergel1,2 () 1 2
Chemical Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA Department of Nuclear Engineering, University of California, Berkeley, CA 94720, USA
© Tsinghua University Press and Springer-Verlag GmbH Germany, part of Springer Nature 2020 Received: 10 May 2020 / Revised: 17 June 2020 / Accepted: 26 June 2020
ABSTRACT Radiotherapy, where ionizing radiation is locally delivered either through an external beam or by surgically implanting radionuclidebased seeds in the tumor, is one of the gold standard treatments for cancer. Due to the non-selective nature of radiation, healthy tissue surrounding the cancerous region is usually affected by the treatment. Hence, new strategies, including targeted alpha therapy, are being studied to improve the selectivity of the treatment and minimize side effects. Several challenges, however, limit the current development of targeted radiotherapy, such as the functionalization of the therapeutic agent with targeting vectors and controlling the release of recoiling daughters. Nanoparticles offer unique opportunities as drug delivery vehicles, since they are biocompatible, enhance the cellular uptake of drugs, and are easily functionalized with targeting molecules. In this review, we examine how nanoparticles can be used for targeted radiotherapy, either as sensitizers of external beams or as delivery vehicles for therapeutic radionuclides. We describe the clinical relevance of different types of nanoparticles, followed by an analysis of how these nanoconstructs can solve some of the main limitations of conventional radiotherapy. Finally, we critically discuss the current situation of nanoparticle-based radiotherapy in clinical settings and challenges that need to be overcome in the future for further development of the field.
KEYWORDS radiotherapy, targeted cancer radiotherapy, nanoparticles, cancer, targeted alpha therapy, external beam
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Introduction
Therapy based on ionizing radiation is used to treat primary tumors as well as to prevent cancer relapse after the main tumor has been surgically removed [1–3]. For example, radiotherapy and surgery are the standard protocols to treat risky localized prostate cancer patients [1]. Radiotherapy can also interact synergistically with other treatments; it is frequently applied either before, during or after chemotherapy [4–6]. Radiation can be delivered to cancer cells either externally via a beam or internally (brachytherapy) through an implanted radiation source (Fig. 1) [7, 8]. Ionizing radiation damages multiple intracellular components, such as DNA, through molecule ionization that generates a free radical cascade [9, 10]. Although it is very effective at damaging tumor cells, ionizing radiation also affects surrounding healthy tissue. Hence, control over the administered radiation dose is fundamental to minimizing toxicity for normal tissues, and new strategies to target cancer cells are under investiga
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