Nanoparticle-Mediated Radiosensitization in Breast Cancer: A Systematic Review of Preclinical Evidence and Translational Challenges
Abstract
Radiotherapy is a cornerstone of breast cancer treatment, but its efficacy is frequently limited by intrinsic and acquired radioresistance as well as dose-limiting toxicity to surrounding normal tissues. Nanoparticle-mediated radiosensitization has emerged as a promising strategy to enhance the therapeutic index of irradiation by combining physical dose amplification with biological, microenvironmental, and immunological modulation. In this systematic review, we evaluated preclinical evidence on nanoparticle-mediated radiosensitization in breast cancer, with emphasis on nanoplatform design, mechanistic patterns, therapeutic efficacy, and translational relevance. A total of 66 studies published between 2015 and 2026 were included. The identified systems encompassed a broad range of materials, including gold-, silver-, platinum-, bismuth-, gadolinium-, polymer-, lipid-, and hybrid-based nanoplatforms, frequently incorporating targeting ligands, catalytic components, biomimetic coatings, or therapeutic payloads. Enhanced radiation responses were most commonly associated with high-atomic-number (high-Z)-mediated energy deposition, increased reactive oxygen species generation, and enhanced DNA damage persistence. Additional mechanisms, including redox modulation, hypoxia targeting, regulated cell death, and immune activation, reflect the evolution of nanoparticle-assisted radiotherapy from predominantly physical radioenhancement toward multifunctional physicobiological…
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