Bacterial outer membrane vesicles encapsulating oncolytic virus for targeted nose-to-brain delivery

Abstract

Oncolytic virus therapy, as an emerging anti-tumor biological therapy, has demonstrated significant therapeutic potential for brain tumors in clinical studies. However, due to the special anatomical barrier of the brain tissue, the application of oncolytic viruses is currently limited to the intracranial administration route, which restricts its clinical convenience and safety. Herein, we propose a biomimetic composite strategy, utilizing the characteristic of Escherichia coli K1 (EC-K1) that can efficiently enter the brain through the nasal-brain pathway, and modifying its outer membrane vesicles (OMVs) on the surface of oncolytic adenovirus serotype 11 (Ad11@dOMV). The results show that the efficiency of Ad11@dOMV crossing the nasal-brain barrier after nasal administration in vivo is about 581 times higher than that of the unmodified virus, and it achieves comparable anti-tumor efficacy to intracranial administration in the lung cancer brain metastasis model. This strategy provides a feasible path for non-invasive nasal delivery of oncolytic viruses.