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Sphingosine 1‐Phosphate Liposomes for Targeted Nitric Oxide Delivery to Mediate Anticancer Effects against Brain Glioma Tumors
Author(s) -
Liu Yang,
Wang Xiao,
Li Jing,
Tang Jian,
Li Bin,
Zhang Yu,
Gu Ning,
Yang Fang
Publication year - 2021
Publication title -
advanced materials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 10.707
H-Index - 527
eISSN - 1521-4095
pISSN - 0935-9648
DOI - 10.1002/adma.202101701
Subject(s) - glioma , liposome , drug delivery , prodrug , s1pr1 , blood–brain barrier , nitric oxide , transcytosis , brain tumor , sphingosine , sphingosine 1 phosphate receptor , pharmacology , cancer research , sphingosine 1 phosphate , in vivo , targeted drug delivery , biology , receptor , materials science , medicine , endocytosis , biochemistry , nanotechnology , pathology , neuroscience , central nervous system , vascular endothelial growth factor , vascular endothelial growth factor a , vegf receptors , microbiology and biotechnology
Specifically targeting glioblastoma multiforme (GBM) blood vessels and actively enhancing the permeability of the brain–blood–tumor barrier (BBTB) are two extremely difficult challenges currently hindering the development of effective therapies against GBM. Herein, a liposome drug delivery system (S1P/JS‐K/Lipo) is described, which delivers the nitric oxide (NO) prodrug JS‐K, O 2 ‐(2,4‐dinitrophenyl) 1‐[(4‐ethoxycarbonyl) piperazin‐1‐yl] diazen‐1‐ium‐1,2‐diolate, to GBM tumors using sphingosine‐1‐phosphate (S1P)‐signaling molecules as active targeting lipid ligands. It is revealed that S1P/JS‐K/Lipo actively penetrates the BBTB, aided by caveolin‐1‐mediated transcytosis, and it is demonstrated that the system specifically interacts with S1P receptors (S1PRs), which are highly expressed on GBM cells. Nondestructive ultrasound imaging in GBM mouse models is also utilized to observe microsized NO bubble production from JS‐K, as catalyzed by the glutathione S ‐transferases (GSTs) resident in GBM cells. Given that these NO bubbles strongly promote GBM cell death in vivo, the S1PR‐targeted liposome delivery system—which successfully achieves BBTB penetration and tumor targeted delivery of a complex multicomponent drug regimen—represents a promising approach for targeted therapies against GBM and other carcinomas characterized by elevated S1PR expression.