Multifunctional Biomimetic Liposomes with Improved Tumor-Targeting for TNBC Treatment by Combination of Chemotherapy, Anti-Angiogenesis and Immunotherapy.

Abstract

Triple negative breast cancer (TNBC) featuring high relapses and metastasis showed limited clinical therapeutic efficiency with chemotherapy for the extremely complex tumor microenvironment (TME), especially angiogenesis and immunosuppression. Combination of anti-angiogenesis and immunotherapy holds promise for effective inhibition of tumor proliferation and invasion, while it remains challenging for specific targeting drug delivery to tumors and metastatic lesions. Here, a multifunctional biomimetic liposome loading Gambogic acid (G/R-MLP) was developed using Ginsenoside Rg3 (Rg3) to substitute cholesterol and cancer cell membrane coating, which was designed to increase long-circulating action by a low immunogenicity and specifically deliver Gambogic acid (GA) to tumor site and metastatic lesions by homologous targeting and glucose transporter (GLUT) targeting. After G/R-MLP accumulated in the primary tumors and metastatic nodules, it synergistically enhanced the anti-tumor efficacy of GA, effectively suppressing the tumor growth and lung metastasis by killing tumor cells, inhibiting tumor cell migration and invasion, achieving anti-angiogenesis and improving the anti-tumor immunity. All in all, the strategy combining chemotherapy, anti-angiogenesis and immunotherapy improved therapeutic efficiency and prolonged survival, providing a new perspective for the clinical treatment of TNBC. This article is protected by copyright. All rights reserved.