Developing a Versatile Multiscale Therapeutic Platform for Osteosarcoma Synergistic Photothermo-Chemotherapy with Effective Osteogenicity and Antibacterial Capability.

Abstract

Osteosarcoma is a devastating malignant neoplasm that seriously threatens human health. After an osteosarcoma resection, the simultaneous treatment of tumor recurrence, postoperative infection, and large bone loss remains a formidable challenge clinically. Herein, a versatile multiscale therapeutic platform (Fs-BP-DOX@PDA) is engineered based on NiTi alloys with versatile properties for near-infrared (NIR)-mediated osteosarcoma synergistic photothermo-chemotherapy, bone regeneration, and bacterial elimination. First, an intriguing method for fabricating groovelike micro-nanostructures (Fs-NiTi) through femtosecond laser direct writing to enhance osseointegration with strong contact guidance is proposed. Then, black phosphorus (BP) nanosheets as gratifying photothermal conversion agents, osteogenetic agents, and a drug delivery platform are decorated on Fs-NiTi to construct multiscale hierarchical structures (Fs-BP). Finally, the polydopamine (PDA) modification is utilized to enhance the photothermal performance, biocompatibility, and chemical stability of doxorubicin (DOX)-loaded Fs-BP and endow NIR/pH-dual-responsive DOX release properties. Fs-BP-DOX@PDA effectively induces tumor cell (Saos-2 and MDA-MB-231) death in vitro, completely eradicates osteosarcoma in mice, and observably promotes bone-regeneration bioactivity. Furthermore, it possesses prominent antibacterial efficiencies toward Staphylococcus aureus (99.2%) and Pseudomonas aeruginosa (99.6%). Overall, this work presents a smart comprehensive fabrication methodology to construct a versatile multiscale therapeutic platform for multimodal osteosarcoma treatment and biomedical tissue engineering.