A Novel Anti-PD-L1 Functionalized Protopanaxadiol-Liposome Loading Paclitaxel for Synergistic Immunochemical Therapy of Triple-Negative Breast Cancer

Chemotherapy combined with immune checkpoint blockade (ICB) has shown a significant therapeutic effect in triple negative breast cancer (TNBC). However, due to the existence of a tumor immunosuppressive microenvironment and the influence of the autoregulatory mechanism of related receptors, the response to ICB therapy is still limited; there is a low response rate of patients, and the clinical treatment success rate is still less than 20%. In this study, we developed novel chemo-immunosynergistic therapies aimed at safe and effective treatment of TNBC. A novel liposome loaded paclitaxel (PTX) was prepared using protopanaxadiol (PPD) as a membrane material to reshape the tumor microenvironment (TME) and improve the delivery of PTX in vivo. In vitro studies have demonstrated that PPD-PTX-lipo can target and reshape the TME, inhibit tumor cell proliferation and migration, and induce tumor cell apoptosis. Anti-PD-L1 was further modified on the surface of the liposome (anti-PD-L1-PPD-PTX-lipo) for chemotherapy and immunosynergistic treatment. The combination of anti-PD-L1 and liposome further promotes the uptake of liposome by tumor cells and at the same time promotes the degradation of PD-L1 in vivo to achieve long-term immunotherapy. In summary, this study has developed a highly effective immunochemical synergistic therapy that provides a new strategy for TNBC treatment.