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Title of Journal: Pharm Res

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Abbravation: Pharmaceutical Research

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Springer US

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DOI

10.1007/bf01452223

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1573-904X

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Targeting Endocytosis and Lysosomal Delivery of

Authors: Janet Hsu Janet Hoenicka Silvia Muro
Publish Date: 2014/10/16
Volume: 32, Issue: 4, Pages: 1264-1278
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Abstract

Delivery of therapeutics to neurons is paramount to treat neurological conditions including many lysosomal storage disorders However key aspects of drugcarrier behavior in neurons are relatively unknown the occurrence of noncanonical endocytic pathways present in other cells whether carriers that traverse the blood–brain barrier are contrarily retained within neurons if neuronsurface receptors are accessible to bulky carriers compared to small ligands or if there are differences regarding neuronal compartments neuron body vs neurites pertaining said parameters We have explored these questions using model polymer nanocarriers targeting intercellular adhesion molecule1 ICAM1ICAM1 expression and nanocarrier binding was enhanced in altered TNFα vs control conditions While small ICAM1 ligands antiICAM preferentially accessed the cell body antiICAM nanocarriers bound with faster kinetics to neurites yet reached similar saturation over time AntiICAM nanocarriers were also endocytosed with faster kinetics and lower saturation levels in neurites Nonclassical cell adhesion molecule CAM endocytosis ruled uptake and neuritetocell body transport was inferred Nanocarriers trafficked to lysosomes delivering active enzymes dextranase with substrate reduction in a lysosomalstorage disease model

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