Singlet oxygen-responsive nanoplatform for synergetic photodynamic-immunotherapy guided by NIR-II imaging

Triple-negative breast cancer (TNBC) presents significant treatment challenges due to its lack of clear molecular targets and immunosuppressive tumor microenvironment (TME). This study reports the development of a light-triggered biomimetic nanodelivery system (OPTC-RNP@CM) to overcome these hurdles. The system integrates a semiconducting polymer for second near-infrared (NIR-II) imaging, a photosensitizer (Ce6), and CRISPR/Cas9 ribonucleoprotein targeting PD-L1 via a singlet oxygen-cleavable linker. Coated with homologous tumor cell membranes for enhanced targeting, the nanoparticles accumulate at the tumor site. Upon NIR irradiation, generated singlet oxygen simultaneously triggers the release of Cas9 RNP for PD-L1 gene editing and induces photodynamic therapy (PDT). This dual action promotes immunogenic cell death (ICD) and, synergistically with PD-1/PD-L1 pathway blockade, effectively remodels the immunosuppressive TME, amplifying the antitumor immune response. This versatile platform offers a promising strategy for precise and enhanced immunotherapy against TNBC.