Engineering Macrophage Exosome Disguised Biodegradable Nanoplatform for Enhanced Sonodynamic Therapy of Glioblastoma.

Sonodynamic therapy (SDT) exhibits high tissue penetration and negligible radiation damage to normal tissues, and thus emerges as a promising cancer therapeutic modality for glioblastoma (GBM). However, the blood-brain barrier (BBB) and hypoxic microenvironment greatly limit the SDT efficiency. In this work, a biodegradable nanoplatform (termed as CSI) is fabricated by encapsulating catalase (CAT) into silica nanoparticles (CAT@SiO 2 ) for tumor hypoxia relief, and then loaded with the sonosensitizer indocyanine green (ICG). Inspired by the ability of macrophages to cross the BBB, CSI is further coated with AS1411 aptamer-modified macrophage exosomes to form CSI@Ex-A, which possesses efficient BBB penetration and good cancer-cell-targeting capability. After tumor cell endocytosis, highly expressed glutathione (GSH) triggeres biodegradation of the nanoplatform and the released CAT catalyzes hydrogen peroxide (H 2 O 2 ) to produce O 2 to relieve tumor hypoxia. The GSH depletion and O 2 self-supplying effectively enhances the SDT efficiency both in vitro and in vivo. In addition, the resulting CSI@Ex-A exhibits good biocompatibility and long circulation time. These findings demonstrate that CSI@Ex-A may serve as a competent nanoplatform for GBM therapy, with potential for clinical translation.