Abstract
Surface charge plays a fundamental role in determining the fate of a nanoparticle, and any encapsulated contents, in vivo. Herein, we describe, and visualise in real time, light-triggered switching of liposome surface charge, from neutral to cationic, in situ and in vivo (embryonic zebrafish). Prior to light activation, intravenously administered liposomes, composed of just two lipid reagents, freely circulate and successfully evade innate immune cells present in the fish. Upon in situ irradiation and surface charge switching, however, liposomes rapidly adsorb to, and are taken up by, endothelial cells and/or are phagocytosed by blood resident macrophages. Coupling complete external control of nanoparticle targeting together with the intracellular delivery of encapsulated (and membrane impermeable) cargos, these compositionally simple liposomes are proof that advanced nanoparticle function in vivo does not require increased design complexity but rather a thorough understanding of the fundamental nano-bio interactions involved.
Highlights
Surface charge plays a fundamental role in determining the fate of a nanoparticle, and any encapsulated contents, in vivo
We have previously shown that i.v. administered liposomes with neutral surface charge, and optimally 100 nm in size, tend to freely circulate in embryonic zebrafish (Danio rerio)[25]
To achieve intracellular delivery of drugs, encapsulated payloads should remain entrapped within liposomes, before, during and after light activation
Summary
Surface charge plays a fundamental role in determining the fate of a nanoparticle, and any encapsulated contents, in vivo. We describe, and visualise in real time, light-triggered switching of liposome surface charge, from neutral to cationic, in situ and in vivo (embryonic zebrafish). Following intravenous (i.v.) injection, nanoparticles with high surface charge density, either anionic or cationic, are rapidly cleared from circulation by specialised cells of the reticulo-endothelial system (RES)[3,4,5]. While usually considered detrimental to in vivo performance, the non-specific, cellular interactions of cationic nanoparticles/complexes (e.g. LipofectamineTM) have been widely exploited to deliver membrane impermeable, (genetic) material across cell membranes in vitro[27,28,29,30]. Following in situ light activation, rapid surface charge switching results in non-specific adsorption and uptake of liposomes across the entire endothelium of the fish, as well as phagocytic uptake in blood resident macrophages. Light triggered surface charge switching does not disrupt liposome integrity and encapsulated, membrane impermeable payloads are successfully transported across cell membranes following surface charge switching
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