A combinational chemo-immune therapy using outer membrane vesicles for enhanced cancer therapy by RGD targeting.

ABSTRACT

Cancer therapies are limited by poor drug penetration that impedes effective tumor treatment. This was overcome in the present study by loading the immune reaction inducing nanocarriers of the bacterial outer membrane vesicles (OMVs) and doxorubicin (DOX) into the natural immunity platform OMV via incubation. Drug accumulation at the tumor site was improved by using the targeting peptide 6-Mal- Arg-Gly-Asp (RGD) on the surface of OMVs to increase internalization via binding to cell surface integrin αvß3. OMVs stimulate immune responses by reversing the immune-suppressive tumor microenvironment (TME) via decreasing TAM and Treg, increasing CD8+ T and M1, and promoting DC maturation. The combination of DOX and OMVs compensates for the shortcomings of monotherapy (e.g., chemotherapy and immunotherapy) and amplifies the therapeutic efficacy of cancer treatment, while aiding selection of novel nanocarriers and development of effective therapeutic regimens.