A siRNA-Assisted Assembly Strategy to Simultaneously Suppress Self and Upregulate Eat-Me Signals for Nanoenabled Chemo-Immunotherapy

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 center dot 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.

Automated summary

The study utilized a siRNA-assisted assembly strategy to deliver siRNA and MTO simultaneously, effectively enhancing phagocytosis of tumor cells by macrophages. This approach promoted antigen presentation and triggered T cell-mediated immune responses, leading to significantly improved antitumor activity in aggressive tumor animal models.