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

Adv Healthc Mater. 2024 Oct;13(26):e2400046. doi: 10.1002/adhm.202400046. Epub 2024 Jun 5.

Abstract

Triple negative breast cancer (TNBC) featuring high relapses and metastasis shows limited clinical therapeutic efficiency with chemotherapy for the extremely complex tumor microenvironment, especially angiogenesis and immunosuppression. Combination of antiangiogenesis 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) is developed using Ginsenoside Rg3 (Rg3) to substitute cholesterol and cancer cell membrane coating, which is 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 targeting. After G/R-MLP accumulates in the primary tumors and metastatic nodules, it synergistically enhances the antitumor efficacy of GA, effectively suppressing the tumor growth and lung metastasis by killing tumor cells, inhibiting tumor cell migration and invasion, achieving antiangiogenesis and improving the antitumor immunity. All in all, the strategy combining chemotherapy, antiangiogenesis, and immunotherapy improves therapeutic efficiency and prolonged survival, providing a new perspective for the clinical treatment of TNBC.

Keywords: Ginsenoside Rg3; biomimetic liposomes; gambogic acid; tumor active targeting; tumor microenvironment.

MeSH terms

  • Angiogenesis Inhibitors* / chemistry
  • Angiogenesis Inhibitors* / pharmacology
  • Animals
  • Biomimetic Materials / chemistry
  • Biomimetic Materials / pharmacology
  • Cell Line, Tumor
  • Female
  • Humans
  • Immunotherapy* / methods
  • Liposomes* / chemistry
  • Mice
  • Mice, Inbred BALB C
  • Neovascularization, Pathologic / drug therapy
  • Triple Negative Breast Neoplasms* / drug therapy
  • Triple Negative Breast Neoplasms* / pathology
  • Triple Negative Breast Neoplasms* / therapy
  • Xanthones* / chemistry
  • Xanthones* / pharmacology

Substances

  • Liposomes
  • Xanthones
  • Angiogenesis Inhibitors
  • gambogic acid