Hybrid Cellular Nanovesicles Block PD‐L1 Signal and Repolarize M2 Macrophages for Cancer Immunotherapy

• DOI: 10.1002/smll.202311702
• Publication Date: 2024-03-08T10:49:37Z
• Authors: Chenchen Zhao; Yuanwei Pan; Lujie Liu; Jing Zhang; Xianjia Wu; Yu Liu; Xing‐Zhong Zhao; Lang Rao
• Keywords: Cancer Immunotherapy; Immune checkpoint; Immunosuppression

Abstract The PD1/PD‐L1 immune checkpoint blocking is a promising therapy, while immunosuppressive tumor microenvironment (TME) and poor penetration of therapeutic antibodies limit its efficacy. Repolarization tumor‐associated macrophages (TAMs) offers potential method to ameliorate immunosuppression TME further boost T cell antitumor immunity. Herein, hybrid membrane biomimetic nanovesicles (hNVs) are developed by fusing M1 macrophage‐derived (M1‐NVs) PD1‐overexpressed cell‐derived (PD1‐NVs) improve cancer immunotherapy. M1‐NVs promote the transformation M2‐like TAMs M1‐like phenotype increase release pro‐inflammatory cytokines, resulting in improved TME. Concurrently, PD1‐NVs block pathway, which boosts immunotherapy when combined with M1‐NVs. In breast mouse model, hNVs efficiently accumulate at site after intravenous injection significantly inhibit growth. Mechanically, CD8 + lymphocytes twofold treatment, indicating effective activation. These results suggest as strategy integrate improvement blockade for