A smart DNA hydrogel for isolation of bacterial outer membrane vesicles and localized cancer immunotherapy

Bacterial outer membrane vesicles (OMVs) have shown great potential in cancer immunotherapy. The isolation of OMVs from complex media with high purity and high bioactivity is the prerequisite of therapeutic applications, which remains highly challenging. Herein, we report a smart DNA hydrogel for the efficient isolation of OMVs from bacterial culture medium, which is further applied for localized cancer immunotherapy. The DNA hydrogel is constructed through the cross-linking of two ultralong DNA chains generated via rolling circle amplification (RCA). One chain contains polyvalent GN6 aptamer for the specific capture of OMVs, and the other contains polyvalent programmed death-1 (PD-1) aptamer for the blocking of PD-1 immune checkpoint on the surface of T lymphocytes. The OMVs capsulated by DNA hydrogel maintain high immunostimulatory bioactivity. In the mouse model of melanoma, this OMVs-containing DNA hydrogel shows a remarkable tumor inhibition rate of ∼95%. This smart DNA hydrogel represents a promising biomedical platform for the efficient isolation of bacterial-derived OMVs, and provides a powerful strategy for cancer immunotherapy.