Harnessing PD-1 cell membrane-coated paclitaxel dimer nanoparticles for potentiated chemoimmunotherapy

Abstract

Chemoimmunotherapy has emerged as a promising strategy for improving the efficacy of cancer treatment. Herein, we present PD-1 receptor-presenting membrane-coated paclitaxel dimers nanoparticles (PD-1@PTX₂ NPs) for enhanced treatment efficacy. PD-1 cell membrane-cloaked PTX dimer exhibited effective cellular uptake and increased cytotoxicity against cancer cells. PD-1@PTX₂ NPs could selectively bind with PD-L1 ligands expressed on breast cancer cells. Our nanoparticles exhibit a remarkable tumor growth inhibition rate of 71.3% in mice bearing 4T1 xenografts and significantly prolong survival in mouse models of breast cancer. Additionally, our nanoparticles promoted a significant 3.2-fold increase in CD8⁺ T cell infiltration and 73.7% regulatory T cell (Treg) depletion within tumors, boosting a robust antitumor immune response. These findings underscore the potential of utilizing immune checkpoint receptor-presented PTX nanoparticles to enhance the efficacy of chemoimmunotherapy, providing an alternative approach for improving cancer treatment.

Keywords: Cell membrane; Chemoimmunotherapy; Drug delivery; PD-1; Paclitaxel dimer.