Neutrophil-Mediated Delivery Platforms for Synergistic Chemo-Immunotherapy of Non-Small-Cell Lung Cancer Therapy.

Abstract

Traditional nanocarriers possess good therapeutic efficacy in the treatment of non-small-cell lung cancer (NSCLC), but usually suffer from high immunogenicity, poor biosafety, and low targeting. In this work, a neutrophil-mediated delivery platform constructed from neutrophils (NEs) and paclitaxel/transforming growth factor-β (TGF-β) siRNA loaded cationic liposome, namely, siTGFβ-PLP-NEs, is fabricated for the combination therapy of NSCLC via synergistic chemo-immunotherapy. siTGFβ-PLP-NEs can be targeted to the tumor site and effectively release paclitaxel and siTGFβ, which is conducive to simultaneously inhibiting the proliferation of tumor cells and the expression of TGF-β. The experimental results demonstrate that siTGFβ-PLP-NEs can prevent the transition of tumor-associated NEs from an anti-tumor (N1) phenotype to a pro-tumor (N2) phenotype, enhance CD8⁺ T cell infiltration, and reduce regulatory T cell (Treg) infiltration, which provides a great promising combination therapy option to use neutrophil-mediated systems as a general-purpose delivery platform for the treatment of NSCLC.