Polymeric Nanoparticles Enable CRISPR/Cas9-Mediated CD24 Silencing to Enhance Immunotherapy in Triple-Negative Breast Cancer
발표자
ZHANG ZHENGZHENG (Chonnam National University)
연구책임자
남주택 (Chonnam National University)
공동저자
ZHANG ZHENGZHENG (Chonnam National University), 남주택 (Chonnam National University)
초록
내용
Immune evasion and limited response to immunotherapy remain major challenges in triple-negative breast cancer (TNBC). CD24 is highly expressed on tumor cells and interacts with Siglec-10 on immune cells, which suppresses macrophage-mediated phagocytosis and makes it a potential immune checkpoint (ICB) target. Herein, we developed a polyethyleneimine (PEI) based nanoparticle system (PDGCS) to deliver CRISPR/Cas9 plasmid for targeted CD24 gene silencing. Our PDGCS nanoparticles enable stable gene delivery and efficient intracellular genome editing, which effectively block the CD24-Siglec-10 signaling. Consequently, enhanced phagocytosis by tumor-associated macrophages. Moreover, CD24 knockdown significantly improve the therapeutic efficacy of ICB immunotherapy in vivo. This study demonstrates a safe and effective polymeric CRISPR delivery platform and provides a promising strategy for synergistic immunotherapy in TNBC.