PT - JOURNAL ARTICLE AU - Cai, Qi AU - Li, Xiaoqing AU - Xiong, Hejian AU - Fan, Hanwen AU - Gao, Xiaofei AU - Vemireddy, Vamsidhara AU - Margolis, Ryan AU - Li, Junjie AU - Ge, Xiaoqian AU - Giannotta, Monica AU - Dejana, Elisabetta AU - Hoyt, Kenneth AU - Bachoo, Robert AU - Qin, Zhenpeng TI - Optical Modulation of Blood-Brain-Tumor Barrier Permeability Enhances Drug Delivery in Diverse Preclinical Glioblastoma Models AID - 10.1101/2022.06.07.495027 DP - 2022 Jan 01 TA - bioRxiv PG - 2022.06.07.495027 4099 - http://biorxiv.org/content/early/2022/06/09/2022.06.07.495027.short 4100 - http://biorxiv.org/content/early/2022/06/09/2022.06.07.495027.full AB - Glioblastoma multiforme (GBM) is the most prevalent malignant tumor in the central nervous system. It has diverse phenotypes, including diffuse single-cell infiltration in which the tumor cells co-opt the normal microvasculature, and the neovascularization of an expanding tumor mass. The blood-brain-tumor barrier (BBTB) is a significant obstacle to GBM treatment and restricts entry of most FDA-approved effective oncology drugs. Herein, we report that picosecond laser excitation of vascular-targeted plasmonic gold nanoparticles (AuNPs) can non-invasively and reversibly modulate the BBTB permeability (optoBBTB). OptoBBTB enhances the delivery of paclitaxel (Taxol) in two genetically engineered glioma models (GEMM) that span the spectrum of GBM phenotypes. OptoBBTB followed by Taxol delivery effectively suppresses tumor growth and prolongs the survival time of both GEMM. Moreover, our results raise the possibility that paclitaxel, which is amongst the most widely used oncology drugs because of its proven efficacy but has been abandoned for GBM following its failure to efficacy in early phase clinical trials due to poor blood-brain barrier (BBB) penetration, could now be reconsidered in combination with strategies to increase BBB permeability. In summary, optoBBTB is a novel and effective approach to increase the delivery of therapeutics with limited BBB permeability to treat neoplastic and non-neoplastic brain diseases.Competing Interest StatementThe authors have declared no competing interest.