Astragalus polysaccharide-based nano-platforms loading PTX to boost chemo-immunotherapy for triple-negative breast cancer with intrinsic GLUT-targeting ability and immunoregulatory activity

Abstract

Chemo-immunotherapy shows great promises for triple-negative breast cancer (TNBC) treatment, including PTX. However, the chemo-immunotherapy of PTX is limited, due to its upregulation of PD-L1 expression on tumor cells and bone marrow suppression. In addition, nano drug delivery systems of PTX encounter substantial challenges against tumors, such as inefficient encapsulation and inadequate tumor targeting efficacy. Here, PTX-loaded nanoparticles (APS-PTX NPs) based on astragalus polysaccharide (APS) was successfully developed to address these challenges. In APS-PTX NPs, APS could form amphiphilic polymers to highly load PTX, in which APS worked as the carrier, active targeting ligand, immunoregulator and chemotherapy adjuvant at the same time. Compared to PTX or Lipusu® (PTX-Lipo), APS-PTX NPs increased cellular uptake by binding to high expressed glucose transporter of 4T1 cells, and synergistically enhanced cytotoxicity of PTX. Meanwhile, APS-PTX NPs induced immunogenic cell death to induce DC maturation and decreased PD-L1 expression of 4T1 cells. In the TNBC model, APS-PTX NPs synergistically activates a potent systemic anti-tumor immunity, effectively inhibiting tumor growth and lung metastasis, and alleviating the reduction of white blood cell induced by PTX. Overall, the multifunctional nanoplatforms based on APS could overcome the harsh tumor biological barriers, and boost chemo-immunotherapy for TNBC treatment.