Biomimetic etoposide-loaded PLGA nanoparticles induce immunogenic cell death against colorectal cancer

Colorectal cancer (CRC) is a prevalent malignancy, ranking third in incidence among all cancers. The inherent heterogeneity and the immunosuppressive tumor microenvironment (ITME) of CRC poses significant challenges in developing effective treatment strategies. In this study, we found that etoposide (ETO) could induce immunogenic cell death (ICD) in CRC cells, highlighting its potential to activate anti-tumor immunity. To overcome the limitations of ETO's poor solubility and low bioavailability, we developed ETO-loaded poly (lactic-co-glycolic acid) (PLGA) nanoparticles. Additionally, we employed biomimetic modification using CT26 cell-derived membranes to enhance tumor accumulation through homologous targeting and to evade macrophage phagocytosis. In vitro experiments confirmed the enhanced cytotoxicity and ICD characteristics in CT26 cells. In vivo studies further validated the improved tumor targeting, resulting in significant tumor inhibition. Notably, there was a marked increase in the proportion of CD8+T cells in tumors and lymph nodes (LNs), indicating an improved immunosuppressive microenvironment. The construction of ETO-PLGA@CM presents a promising approach for CRC treatment by synergistically activating specific anti-tumor immune responses. [Display omitted] •Etoposide could induce immunogenic cell death in colorectal cancer cells.•PLGA nanoparticles improved the poor solubility and bioavailability of etoposide.•Biomimetic nanoparticles possess homologous targeting and immune evasion capabilities.•ETO-PLGA@CM augmented the therapeutic efficacy with synergistic immune activation.