Intelligent drug codelivery platform for immune microenvironment reconstruction and immunochemotherapy in osteosarcoma treatment

Immunotherapy has emerged as a new strategy for tumor suppression, but its effectiveness is restricted by the immunosuppressive tumor microenvironment (TME) in the context of osteosarcoma treatment. Therefore, a series of therapies focused on immune activation have been introduced as combination treatments with immunotherapy, especially chemotherapies with the ability to induce immunogenic cell death (ICD). In this study, we designed a nanosized platform (^CCHANP_DOX) to codeliver doxorubicin (DOX) and cisplatin (CDDP) to the tumor site for synergistic killing of malignant cells. Due to the ability of DOX to induce ICD, the immunogenicity of the TME was reconstructed via tumor-specific antigen exposure and dendritic cell maturation. Furthermore, ^CCHANP_DOX treatment increased the sensitivity of tumors to anti-programmed cell death-1 (aPD-1). Our in vivo results demonstrated that the combination of ^CCHANP_DOX and aPD-1 not only successfully depressed tumor growth but also inhibited tumor recurrence and lung metastasis. The enhanced anti-tumor effect can be attributed to the activated immune response and established immune memory. This combination may be a potential immunochemotherapy option for osteosarcoma.