In recent years we developed a drug delivery method based on the fusion of liposomes with live cells and this process was controlled by a complementary pair of lipopeptides. While this method is succesful in an in vitro environment, achieving selectivity in vivo is still a challenge. More general, cell-type specific targeting is a common goal in nanoparticle drug delivery, yet for most cell types, in vivo targeting efficiencies remain less than 1%. Here we use a zebrafish model to dynamically assess nanoparticle fate in vivo and uncover targeting specificities of various liposomes composed of naturally occurring phospholipids alone. We identify formulations highly selective for a subset of endothelial cells and through encapsulation of clodronic acid, a cytotoxic and membrane impermeable drug, demonstrate selective deletion of a single blood vessel type in vivo. Mechanistically, we identify endothelial scavenger receptor stabilin-2 as mediator of liposome targeting, extending the function of these receptors to the recognition of neutral nanoparticles. Our findings establish the zebrafish as a powerful model organism for understanding and optimising liposomal drug delivery, reveal a critical importance of lipid composition to in vivo liposome fate and identify a novel drug formulation with potential application in anti-angiogenic therapy.

Selective blood vessel deletion using liposomes: Studying the effect of liposome composition on in vivo behavior

253rd National Meeting (2017)

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