Black Phosphorus-Loaded Manganese Nanosystem Embedded in Thermosensitive Polymer Gels as an Injectable Platform for Osteosarcoma Therapy

Osteosarcoma has the characteristics of rapid recurrence, metastasis, and difficulty in repairing bone defects caused by tumorectomy. A therapeutic strategy with multimode synergistic antitumor effects and benefits for the bone repair are needed. Herein, a multifunctional nanoplatform based on PAH-MnO2@BP nanosheets loaded on thermosensitive gel poly(d,l-lactide)-poly(ethylene glycol)-poly(d,l-lactide) (PDLLA-PEG-PDLLA, PLEL) was designed for in situ osteosarcoma synergy therapy (photothermal/photodynamic/chemotherapy, PTT/PDT/CHT) and bone regeneration. The manganese dioxide loaded on BP NSs converts the surplus hydrogen peroxide into oxygen, ameliorating tumor hypoxia and enhancing the photodynamic effect. Simultaneously, the photothermal effect of BP NSs promotes oxygen transport and controls the release of doxorubicin. Furthermore, the slow degradation of PLEL is beneficial for bone repair and bone regeneration. This hydrogel composite effectively integrates PTT/PDT/CHT therapies, synergistically enhancing tumor efficacy and minimizing the risk of relapse. This study may offer a strategy for the therapeutic approach of osteosarcoma and enlightenment for more precise and customized cancer therapy.