Thermo-sensitive hydrogel-mediated locally sequential release of doxorubicin and palbociclib for chemo-immunotherapy of osteosarcoma

•The ring-opening polymerization of l-Ala NCA was triggered by mPEG45-NH2 to obtain mPEG45-PLAal20, which exhibited suitable sol–gel transition temperature and superior biodegradability, laying the foundation for local injection drug delivery in tumors.•The temperature-sensitive hydrogels exhibited sequential drug release behavior after piggybacking on dual drugs, which synergistically exerted anti-tumor immunotherapeutic effects in osteosarcoma.•Temperature-sensitive hydrogel-based drug delivery systems showed enhanced antitumor and anti-bone destruction effects, reduced pulmonary metastasis, and improved biosafety.