Full encapsulation of oncolytic virus using hybrid erythroctye-liposome membranes for augmented anti-refractory tumor effectiveness

Intravenous delivery of oncolytic virus (OVs) is promising in cancer treatment. Unfortunately, fast clearance of OVs and the severe cytokine release syndrome impede its wide application. It has been shown that nanoparticles coated with cell membranes display less toxicity and slower clearance. However, different from conventional nanoparticles, the characteristic spike-like structure and abundant antigens on the surface make it difficult for intravenously delivered OVs to take advantage of cell membrane coating to shield their surface antigens. To overcome this challenge, we, for the first time, used erythrocyte-lipid hybrid membrane vesicle (erythroliposome) to fully encapsulate OVs for their intravenous delivery. We found that adding artificial membranes to cell membranes reduced the fluidity of the membranes, leading to an extraordinary shielding effect on OV antigens. Consequently, circulation of OVs was significantly prolonged and their oncolytic efficacy to metastatic and refractory tumors was markedly enhanced.