Membrane-anchoring nanoengineered carbon dots as a pyroptosis amplifier for robust tumor photodynamic-immunotherapy

Photodynamic therapy (PDT), as a FDA-approved therapeutic modality, has witnessed substantial advancements in the field of oncology. However, the conventional PDT may suffer poor prognosis due to the transient nature of ROS, excessive phototoxicity, and inducing traditional apoptosis. In this study, a nanoengineered carbon dots (NCDs) was constructed through electrostatic interaction between a positive-charged carbon dots photosensitizers (PCDs) and new indocyanine green (IR820). The introduction of IR820 at variable ratios could change the surface charge and amphiphilic characteristics of NCDs, thereby modulating the membrane-anchoring capability of NCDs. Besides, the J-aggregation of IR820 led to a redshift of fluorescence from NIR-I to NIR-II region, thereby achieving NIR-II imaging. Furthermore, the photoactivity of PCDs was quenched by IR820, with subsequent restoration of PDT occurring contingent on the photobleaching of IR820 via 750 nm laser irradiation. Finally, both in vitro and in vivo studies had demonstrated that under a cascaded laser irradiation, the membrane-targeted NCDs could effectively induce cell pyroptosis, thereby eradicating tumors with minimal side effects while simultaneously activating immune responses to inhibit tumor lung metastasis. This study developed a multifunctional nanoengieering carbon dots and offered novel perspectives for tumor photodynamic-immunotherapy with enhanced controllability, improved efficacy and high security.