1. A siRNA-Assisted Assembly Strategy to Simultaneously Suppress 'Self' and Upregulate 'Eat-Me' Signals for Nanoenabled Chemo-Immunotherapy
- Author
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Senlin Li, Xianzhu Yang, Zhenghai Zhang, Ziyang Cao, Liang Zhao, Xiao-Ding Xu, Dongdong Li, and Yuxi Zhang
- Subjects
biology ,Chemistry ,CD47 ,medicine.medical_treatment ,Melanoma ,Antigen presentation ,General Engineering ,General Physics and Astronomy ,CD47 Antigen ,Immunotherapy ,medicine.disease ,Immune system ,Phagocytosis ,Neoplasms ,Cancer cell ,Cancer research ,medicine ,biology.protein ,Animals ,Gene silencing ,General Materials Science ,RNA, Small Interfering ,Receptors, Immunologic ,Calreticulin - Abstract
Effectively activating macrophages that can engulf cancer cells is a promising immunotherapeutic strategy but remains a major challenge due to the expression of "self" signals (e.g., CD47 molecules) by tumor cells to prevent phagocytosis. Herein, we explored a siRNA-assisted assembly strategy for the simultaneous delivery of siRNA and mitoxantrone hydrochloride (MTO·2HCl) via PLGA-based nanoparticles. The siRNA suppressed a "self" signal by silencing the CD47 gene, while the MTO induced surface exposure of calreticulin (CRT) to provide an "eat-me" signal. The siRNA-assisted assembly strategy synergistically increased the phagocytosis of tumor cells by macrophages, promoted effective antigen presentation, and initiated T cell-mediated immune responses in two aggressive tumor animal models of melanoma and colon cancer, eventually achieving significantly improved antitumor activity. This study provides a straightforward codelivery strategy to simultaneously suppress "self" and upregulate "eat-me" signals to potentiate macrophage-mediated immunotherapy.
- Published
- 2021