Upconversion Nanoparticle-Based Cell Membrane-Coated cRGD Peptide Bioorthogonally Labeled Nanoplatform for Glioblastoma Treatment

Glioblastoma is hard to be eradicated partly because of the obstructive blood-brain barrier (BBB) and the dynamic autophagy activities of glioblastoma. Here, hydroxychloroquine (HDX)-loaded yolk-shell upconversion nanoparticle (UCNP)@Zn_0.5Cd_0.5S nanoparticle coating with the cyclic Arg-Gly-Asp (cRGD)-grafted glioblastoma cell membrane for near-infrared (NIR)-triggered treatment of glioblastoma is prepared for the first time. UCNPs@Zn_0.5Cd_0.5S (abbreviated as YSN, yolk-shell nanoparticle) under NIR radiation will generate reactive oxygen species for imposing cytotoxicity. HDX, the only available autophagy inhibitor in clinical studies, can enhance cytotoxicity by preventing damaged organelles from being recycled. The cRGD-decorated cell membrane allowed the HDX-loaded nanoparticles to efficiently bypass the BBB and specifically target glioblastoma cells. Exceptional treatment efficacy of the NIR-triggered chemotherapy and photodynamic therapy was achieved in U87 cells and in the mouse glioblastoma model as well. Our results provided proof-of-concept evidence that HDX@YSN@CCM@cRGD could overcome the delivery barriers and achieve targeted treatment of glioblastoma.