Intestinal Probiotic Lysate Modified Bifunctional Nanoparticle for Efficient Colon Cancer Immunotherapy.

In cancer immunotherapy, gene therapy has become a promising strategy through the introduction of immunostimulatory components into its formulation. However, ideal non-viral gene delivery platforms capable of simultaneously maintaining a high delivery efficiency and immune activation are still in demand. As an intestinal probiotic, has potential correlation with cancer progression. Its unique antigenicity also confers its immunomodulatory activity. We engineered a new non-viral siRNA delivery system, DMPLAC. By wrapping the lysate of , it is expected to enhance the anti-cancer immunostimulatory properties. Supported by certain internalization pathways, the prepared DMPLAC nanoparticles showed high siRNA delivery efficiency in vitro (up to 97.62%). They also strongly promoted the maturation and activation of immune cells, including dendritic and T cells, both in vitro and in vivo. By loading siRNA targeting the immune checkpoint CD47 gene, the DMPLAC/siCD47 complex strongly suppressed the growth of multiple colon cancer models through local administration with high safety. Our study developed a novel intestinal probiotic lysate-based gene delivery system with dual immunomodulatory abilities, suggesting a potential strategy for cancer immunotherapy.