Protein corona-guided delivery of dextran-PLGA NPs for enhanced dendritic cell uptake, maturation and improved cancer immunotherapy.

The formation of a protein corona (PC) significantly influences the behavior of nanoparticles (NPs) in biological fluids; however, its impact on immune modulation and therapeutic efficacy has not been completely understood. The dextran coating of NPs has demonstrated promising effects, including complement system activation and enhanced immune cell uptake. The stimulator of interferon genes (STING) pathway plays a vital role in coordinating innate and adaptive immunity, making STING agonists attractive candidates for cancer immunotherapy. In this study, we developed dextran-coated PLGA nanoparticles loaded with SR717 (Dex-PLGA@SR717 NPs) for enhanced uptake by immature dendritic cells (iDCs) and for promoting tumor-targeted immune activation. Following incubation with human serum (HS), Dex-PLGA NPs formed a PC enriched in the complement component C3, which resulted in superior cellular internalization compared with uncoated PLGA NPs. The significant role of Dex-PLGA@SR717 NPs in promoting iDC maturation and enhancing antigen presentation was confirmed through in vitro studies. This facilitated robust T cell activation and cytotoxicity against B16F10 melanoma cells. Biodistribution analysis revealed preferential accumulation of Dex-PLGA@SR717 NPs in immune-related organs, such as the spleen and lymph nodes, further supporting their immunostimulatory potential. In a murine tumor model, intravenous administration of Dex-PLGA@SR717 NPs (10 mg/kg SR717) was observed to effectively suppressed tumor growth by eliciting a potent antitumor immune response. These findings highlight the potential of Dex-PLGA@SR717 NPs as a promising immunotherapeutic nanoplatform for enhancing dendritic cell-mediated cancer treatment.