Engineering Study on Targeted Therapy of Osteosarcoma Using Tripterine Loaded Polydopamine Mesoporous Microspheres Combined with Photothermal Therapy.

PURPOSE: Osteosarcoma poses significant clinical challenges due to its high recurrence, metastatic potential, and poor prognosis. Celastrol (CLT), known for its antitumor, immunomodulatory, and osteogenic regulatory properties, has garnered substantial interest. Developing a targeted CLT delivery system is critical to enable precise drug release, integrate photothermal therapy, remodel the tumor microenvironment, and improve post-surgical treatment and repair in osteosarcoma. METHODS: Using emulsion-induced interface assembly, we synthesized mesoporous polydopamine-polyethylene glycol (MPDA-PEG) nanospheres and loaded them with celastrol to fabricate the targeted system MPDA-PEG-CLT. We characterized the nanospheres' physicochemical properties and evaluated MPDA-PEG-CLT's efficacy in synergistic drug-photothermal therapy for osteosarcoma through in vitro and in vivo experiments. RESULTS: MPDA-PEG-CLT achieved a drug loading capacity of ~14% and a photothermal conversion efficiency of 37.6% under 808 nm NIR irradiation, which enhanced celastrol release. The system induced osteosarcoma cell apoptosis, promoted bone marrow mesenchymal stem cell (BMSC) differentiation, and ameliorated the lesion microenvironment, resulting in efficient tumor ablation in mice. CONCLUSION: MPDA-PEG-CLT significantly enhances celastrol's targeted delivery efficiency, promotes mitochondrial apoptosis in osteosarcoma cells, synergizes with photothermal therapy to eradicate tumors, and improves the bone tissue microenvironment in lesions. This system offers a promising strategy for post-surgical osteosarcoma treatment and repair.