RT Journal Article
SR Electronic
T1 Optical Modulation of Blood-Brain-Tumor Barrier Permeability Enhances Drug Delivery in Diverse Preclinical Glioblastoma Models
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.06.07.495027
DO 10.1101/2022.06.07.495027
A1 Cai, Qi
A1 Li, Xiaoqing
A1 Xiong, Hejian
A1 Fan, Hanwen
A1 Gao, Xiaofei
A1 Vemireddy, Vamsidhara
A1 Margolis, Ryan
A1 Li, Junjie
A1 Ge, Xiaoqian
A1 Giannotta, Monica
A1 Dejana, Elisabetta
A1 Hoyt, Kenneth
A1 Bachoo, Robert
A1 Qin, Zhenpeng
YR 2022
UL http://biorxiv.org/content/early/2022/06/09/2022.06.07.495027.abstract
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.