Nanoparticle-Based Radiosensitization in Breast Cancer: A Multimodal Approach to Therapy and Immune Regulation.

Radiotherapy is essential for breast cancer treatment, especially after lumpectomy. Its effectiveness, however, is hindered by tumor resistance, which causes recurrence and poorer outcomes. In the last decade, nanoparticle-mediated radiosensitization has emerged as a promising strategy to improve radiotherapy in breast cancer. Metal nanoparticles, such as gold, silver, platinum, and bismuth, increase the localized radiation dose through secondary electron emission and generate reactive oxygen species (ROS). Polymeric, liposomal, and hydrogel nanocarriers deliver radiosensitizers directly to tumors with sustained release. These features increase cytotoxicity and reduce hypoxia-related radioresistance. Nanoparticles also inhibit DNA repair pathways and modulate the tumor microenvironment, which enhances the radiation response. Additionally, nanoparticles can boost the effects of immunotherapy by activating dendritic cells, strengthening immune checkpoint blockade, and promoting anti-tumor immune memory. Recent preclinical studies have shown that combining nanoparticles loaded with natural compounds, such as curcumin, polyphenols, flavonoids, and metformin, increases oxidative stress and radiosensitivity in breast tumors while sparing healthy tissue. We provide an overview of nanoparticle-mediated radiosensitization mechanisms and novel supporting approaches for achieving better tumor responses with reduced toxicity.