Reactive Oxygen Species (ROS) Activated Liposomal Cell Delivery using a Boronate-Caged Guanidine Lipid

被引：6
|
作者：
Lou, Jinchao [1 ]
Qualls, Megan L. [1 ]
Hudson, Macy M. [1 ]
McBee, Dillon P. [1 ]
Baccile, Joshua A. [1 ]
Best, Michael D. [1 ]
机构：
[1] Univ Tennessee, Dept Chem, 1420 Circle Dr, Knoxville, TN 37996 USA
来源：
CHEMISTRY-A EUROPEAN JOURNAL | 2022年 / 28卷 / 46期
基金：
美国国家卫生研究院;
关键词：
caged guanidine; drug delivery; liposomes; reactive oxygen species; targeted cellular delivery; PENETRATING PEPTIDES; HYDROGEN-PEROXIDE; OXIDATIVE STRESS; DRUG-DELIVERY; INTRACELLULAR DELIVERY; PH; CHEMISTRY; CANCER; PHOSPHATIDYLSERINE; METABOLISM;
D O I：
10.1002/chem.202201057
中图分类号：
O6 [化学];
学科分类号：
0703 ;
摘要：
We report boronate-caged guanidine-lipid 1 that activates liposomes for cellular delivery only upon uncaging of this compound by reactive oxygen species (ROS) to produce cationic lipid products. These liposomes are designed to mimic the exceptional cell delivery properties of cell-penetrating peptides (CPPs), while the inclusion of the boronate cage is designed to enhance selectivity such that cell entry will only be activated in the presence of ROS. Boronate uncaging by hydrogen peroxide was verified by mass spectrometry and zeta potential (ZP) measurements. A microplate-based fluorescence assay was developed to study the ROS-mediated vesicle interactions between 1-liposomes and anionic membranes, which were further elucidated via dynamic light scattering (DLS) analysis. Cellular delivery studies utilizing fluorescence microscopy demonstrated significant enhancements in cellular delivery only when 1-liposomes were incubated with hydrogen peroxide. Our results showcase that lipid 1 exhibits strong potential as an ROS-responsive liposomal platform for targeted drug delivery applications.
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页数：7
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