PT  - JOURNAL ARTICLE
AU  - Qi Cai
AU  - Xiaoqing Li
AU  - Hejian Xiong
AU  - Hanwen Fan
AU  - Xiaofei Gao
AU  - Vamsidhara Vemireddy
AU  - Ryan Margolis
AU  - Junjie Li
AU  - Xiaoqian Ge
AU  - Monica Giannotta
AU  - Elisabetta Dejana
AU  - Kenneth Hoyt
AU  - Robert Bachoo
AU  - Zhenpeng Qin
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.