Zinc Sulfide-Based Hybrid Exosome-Coated Autophagy-Mediated H2S-sensitized PDTchemotherapeutic Synergistic Nanoplatform for Targeted Treatment of Glioblastoma Stem-Like Cells in Orthotopic Mouse Glioblastoma Model

Published: July 30, 2020, 10:03 a.m.

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.07.28.226076v1?rss=1 Authors: Mo, J. Abstract: To eliminate glioblastoma stem-like cells, fine core-shell nanoparticles, consisting of hollow ZnS nanoparticles covered by hybrid exosome shell containing exosome and dual responsive iRGD derived phosphatidylserine, and incorporated with autophagic inhibitor hydroxychloroquine (HCQ), denoted as HCQ@ZnS@exo@iRGD were synthesized, characterized and evaluated in vitro and in vivo. The highest release performance of HCQ from HCQ@ZnS@exo@iRGD was attained under low pH and high glutathione conditions. Hybrid exosomes enabled the glioblastoma stem-like cells (GSCs) targeting properties along with excellent permeated ability across BBB were observed both in 3D cells spheroids and in orthotopic mouse glioblastoma model. Visible light source is used to trigger the ROS induction of hollow ZnS nanopartilces. Meanwhile ZnS could produce H2S gas and release its cargo of HCQ as well in situ. Consequently, significant targeted damage to GSCs is achieved due to the combined cytotoxic effects and autophagy-deactivation enabled by HCQ@ZnS@exo@iRGD nanocomposites, indicating its considerable potential for effective GBM treatment. Copy rights belong to original authors. Visit the link for more info