Macrophage Membrane-Coated Liposomes as Controlled Drug Release Nanocarriers for Precision Treatment of Osteosarcoma

Abstract

Osteosarcoma has a relatively high incidence rate among primary malignant tumors, and the survival rate is low. Clinically, surgical resection and chemotherapy are mainly used, which are difficult to utilize to treat metastatic or recurrent osteosarcoma. The combination of chemotherapy and immunotherapy can achieve a better tumor treatment effect. M1 macrophages (M1 Mø) can kill tumor cells and have tumor-targeting and phagocytosis ability, which are an ideal tool for tumor-targeted drug delivery. However, as carriers, living cells have the disadvantages of uncontrollable size, poor tissue permeability, and poor stability. In this study, the M1 macrophage membrane (M1M) was used as the carrier and loaded with MMP-2 (matrix metalloproteinase-2)-sensitive drug-loaded liposomes (GL) to prepare a complex nanovesicle drug delivery system M1M (GL/DOX/TPI-1), with a tumor active targeting function, for combined chemical and immune therapy from doxorubicin (DOX) and tyrosine phosphatase inhibitor 1 (TPI-1). The complex nanovesicles not only retain the tumor-targeting ability from the M1 macrophage membrane but also have the advantages of controllable size, responsive drug release, and high stability. The results of in vivo efficacy test show that the drug delivery system realizes active targeted enrichment in osteosarcoma tissue. Under the response of MMP-2, the internally encapsulated antitumor drugs DOX and TPI-1 from the system are released. This drug delivery system combined with chemical and immune treatment can effectively achieve the aim of the treatment of osteosarcoma.