cGAS-STING activation by nanodelivery of teniposide achieves colorectal cancer chemo-immunotherapy

Colorectal cancer (CRC) has become the second leading cause of cancer-related death. Recently, the strategies to combine chemotherapy and immunotherapy (termed chemo-immunotherapy) have provided new opportunities for treating cancers. The activation of cyclic guanosine monophosphate-adenosine monophosphate synthasestimulator of interferon genes (cGAS-STING) signaling pathway elicits the anticancer immune response. Certain chemotherapy drugs can not only cause cancer cell death, but are also able to trigger the cGAS-STING activation of cancer cells, giving rise to chemo-immunotherapy to cancers. In the present study, teniposide (TEN; a semi-synthetic derivative of podophyllotoxin) caused the cytotoxicity and apoptosis to CRC cells and, during this process, induced the cGAS-STING activation in CRC cells. A nanoformulation was prepared using the aminoethyl anisamide (AEAA)-targeted polyethylene glycol (PEG)-decorated poly(lactic-co-glycolic acid) (PLGA) to achieve CRC-specific delivery of TEN. Consequently, the obtained nanoformulation caused the cancer cell apoptosis, and induced the cGAS-STING-mediated anticancer immune response, collectively leading to chemotherapeutic and immunotherapeutic effects in mice orthotopically grafted by CRC. The present study confirms the capacity of TEN for inducing the cGAS-STING activation of CRC cells, and demonstrates the feasibility of nanodelivery of TEN for CRC chemo-immunotherapy.