ApoE-Corona oncolytic adenovirus nanoparticles enable blood-brain barrier penetration for glioblastoma immunotherapy.

Oncolytic adenovirus (OA) therapy, an emerging cancer immunotherapy, is on the rise. However, intravenous delivery of OA has not yielded success in the treatment of glioblastoma (GBM) due to inefficient blood-brain barrier (BBB) penetration and poor glioma-targeting effectiveness. Therefore, oncolytic adenovirus nanoparticles (OA@Aβ-am NPs) have been successfully designed for efficient targeted delivery to GBM. The prepared platform uses OA as the core and then interacts with apolipoprotein E (ApoE) and LDLR-associated protein 1 (LRP1), which is overexpressed within glioma, as the target. Modified amyloid beta peptide (Aβ-am) actively accumulates ApoE in plasma to form a protein corona and promotes binding to LRP1, thus achieving dual targeting of the BBB and GBM. In addition, systematic studies confirm that OA@Aβ-am NPs possess excellent targeting ability and can prolong the survival of in situ GBM-bearing mice. OA@Aβ-am NPs can induce anti-tumor immune responses after reaching the GBM site, turning the "cold" GBM into a "hot" tumor and causing immunogenic cell death (ICD). In summary, this constructed OA@Aβ-am NP platform provides a promising strategy for oncolytic adenovirus-targeted therapy for GBM.