Light-Enhanced O₂-Evolving Nanoparticles Boost Photodynamic Therapy To Elicit Antitumor Immunity

Breast cancer remains to show high mortality and poor prognosis in women despite of significant progress in recent diagnosis and treatment. Herein, we report the rational design of a highly efficient ultrasmall nanotheranostic agent with excellent photodynamic therapy (PDT) performance to against breast cancer and its metastasis by eliciting antitumor immunity. The ultrasmall nanoagent (3.1 ± 0.4 nm) was fabricated from polyethylene glycol modified Cu_{2- x}Se nanoparticles, β-cyclodextrin, and chlorin e6 under ambient conditions. The resultant nanoplatform (CS-CD-Ce6 NPs) can be passively accumulated into the tumor to exhibit dramatic antitumor efficacy through the excellent PDT effect under near-infrared irradiation. The excellent PDT performance of this nanoplatform is owing to its role as a Fenton-like Haber-Weiss catalyst for the efficient degradation of H₂O₂ within the tumor to release hydroxyl radicals (^·OH) and very toxic singlet oxygen (¹O₂) under irradiation. The generated vast amounts of reactive oxygen species not only killed primary tumor cells but also elicited immunogenic cell death (ICD) to release damage-associated molecular patterns (DAMPs) and induced proinflammatory M1-macrophages polarization. Thereby, antitumor immune responses against the metastasis of breast cancer were robustly evoked. Our work demonstrates that ultrasmall Cu_{2- x}Se nanoparticle-based nanoplatform offers a promising way to prevent cancer metastasis via immunogenic effects through its excellent PDT performance.