Enhancing Proton Therapy Efficacy Through Nanoparticle-Mediated Radiosensitization

Abstract

Proton therapy, characterized by its unique Bragg peak, offers the potential to optimize the destruction of cancer cells while sparing healthy tissues, positioning it as one of the most advanced cancer treatment modalities currently available. However, in comparison to heavy ions, protons exhibit a relatively lower relative biological effectiveness (RBE), which limits the efficacy of proton therapy. The incorporation of nanoparticles for radiosensitization presents a novel approach to enhance the RBE of protons. This review provides a comprehensive discussion of the recent advancements in augmenting the biological effects of proton therapy through the use of nanoparticles. It examines the various types of nanoparticles that have been the focus of extensive research, elucidates their mechanisms of radiation sensitization, and evaluates the factors influencing the efficiency of this sensitization process. Furthermore, this review discusses the latest synergistic therapeutic strategies that integrate nanoparticle-mediated radiosensitization and outlines prospective directions for the future application of nanoparticles in conjunction with proton therapy.

Keywords: RBE; cancer cells; nanoparticle radiosensitization; proton therapy.

Figure 1

Classification of nanoparticles (NPs) with potential radiosensitization effects in proton therapy.

Figure 2

Mechanisms of nanoparticle radiosensitization in proton therapy. (a) Processes of ionization and emission of proton-induced X-rays and Auger electrons resulting from interactions between protons and target atoms. (b) Process of Auger cascade. (c) Illustration of increased physical dose deposition and enhanced radiolysis in cancer cell with presence of nanoparticles.

Figure 3

Nanoparticle-mediated enhancement of physical dose deposition of protons in comparison to conventional methods that do not utilize nanoparticles, specifically within Bragg peak region of proton therapy.

Figure 4

Models of nanoparticle distribution in terms of cellular geometry. (a) Gold nanoparticles randomly distributed in cell nucleus (nucleus model). (b) Gold nanoparticles randomly distributed in whole cell (CellHomo model). (c) Gold nanoparticles randomly distributed in cytoplasm (cytoplasm model). (d) Gold nanoparticles randomly distributed in extracellular media (media model). (e) Gold nanoparticles randomly distributed both inside cell and within extracellular media (complex model). Note that the models depicted in (a–e) were used in simulations by Lin et al. [124]. (f) Gold nanoparticles accumulated in perinuclear configuration (perinuclear model). (g) Gold nanoparticles aggregated in single compartment that sits in cytoplasm (single endosome model). (h) Gold nanoparticles split evenly among four spheres placed at four vertices of tetrahedron (four endosome model). Note that models depicted in (f–h) were used in simulations by Martinov et al. [125].