Cryoshocked Adipocytes Mediated Dual-Modal Strategy Combining Photodynamic Therapy and Triptolide Palmitate for Pulmonary Metastatic Melanoma Treatment.

Pulmonary metastasis represents one of the most prevalent forms of metastasis in advanced melanoma, with mortality rates reaching 70%. Current treatments including chemotherapy, targeted therapy, and immunotherapy frequently exhibit limited efficacy or present high costs. To address these clinical needs, this study presents a biomimetic drug delivery system (Ce6-pTP-CsA) utilizing cryoshocked adipocytes (CsA) encapsulating the prodrug triptolide palmitate (pTP) and the photosensitizer Ce6, exploiting the characteristic of tumor cells to recruit and lipolyze adipocytes for energy. CsA substantially enhances the drug-loading capacity of adipocytes, with its particle size characteristics enabling targeted delivery of pTP to the lungs. The combination of photodynamic therapy (PDT) and pTP activates the caspase cascade, promoting apoptosis in tumor cells. Notably, the cleavage of disulfide bonds in pTP depletes glutathione (GSH), reducing its scavenging effect on reactive oxygen species (ROS) and enhancing the efficacy of PDT. Results demonstrate that Ce6-pTP-CsA effectively inhibits the proliferation and invasion of pulmonary metastatic melanoma cells in vitro and induces apoptosis, while significantly suppressing lung metastasis of SCID mice models in vivo. In conclusion, this novel biomimetic drug delivery system based on adipocytes provides a promising strategy for targeted therapy in pulmonary metastatic melanoma.