Redox-responsive nanoparticles enhance radiation therapy by altering multifaceted radio-resistance mechanisms in human castration-resistant prostate cancer cells and xenografts

•Tumor-reactive hybrid PLMD sensitizes hypoxic human prostate cancer cells to RT.•PLMD enhances RT-induced DNA double strand breaks and inhibits DNA repair mechanism.•PLMD reduces post-RT angiogenesis, vascular abnormality, and tumor growth.•PLMD enhances RT efficacy with prolonged mean survival by 77–93% in PCa xenografts.•PLMD+RT results in 27–40% survival of host while fractionated RT alone does not.