Reactive Oxygen Species (ROS) Activated Liposomal Cell Delivery using a Boronate-Caged Guanidine Lipid.
Jinchao LouMegan L QuallsMacy M HudsonDillon P McBeeJoshua A BaccileMichael D BestPublished in: Chemistry (Weinheim an der Bergstrasse, Germany) (2022)
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.
Keyphrases
- reactive oxygen species
- hydrogen peroxide
- drug delivery
- single cell
- cell death
- dna damage
- cell therapy
- mass spectrometry
- cancer therapy
- nitric oxide
- drug release
- single molecule
- high throughput
- high resolution
- stem cells
- fatty acid
- bone marrow
- mesenchymal stem cells
- simultaneous determination
- optical coherence tomography