Enhanced delivery of α-glucosidase for Pompe disease by ICAM-1-targeted nanocarriers: comparative performance of a strategy for three distinct lysosomal storage disorders.

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TitleEnhanced delivery of α-glucosidase for Pompe disease by ICAM-1-targeted nanocarriers: comparative performance of a strategy for three distinct lysosomal storage disorders.
Publication TypeJournal Article
Year of Publication2012
AuthorsHsu, J, Northrup, L, Bhowmick, T, Muro, S
JournalNanomedicine
Volume8
Issue5
Pagination731-9
Date Published2012 Jul
ISSN1549-9642
Keywordsalpha-Glucosidases, Animals, Antibodies, Monoclonal, Disaccharides, Drug Carriers, Enzyme Replacement Therapy, Glycogen, Glycogen Storage Disease Type II, Human Umbilical Vein Endothelial Cells, Humans, Intercellular Adhesion Molecule-1, Lysosomal Storage Diseases, Lysosomes, Mice, Mice, Inbred C57BL, Molecular Targeted Therapy, Muscle, Skeletal, Nanoparticles, Polymers, Saccharomyces cerevisiae, Tissue Distribution
Abstract

UNLABELLED: Enzyme replacement therapies for lysosomal storage disorders are often hindered by suboptimal biodistribution of recombinant enzymes after systemic injection. This is the case for Pompe disease caused by acid α-glucosidase (GAA) deficiency, leading to excess glycogen storage throughout the body, mainly the liver and striated muscle. Targeting intercellular adhesion molecule-1 (ICAM-1), a protein involved in inflammation and overexpressed on most cells under pathological conditions, provides broad biodistribution and lysosomal transport of therapeutic cargoes. To improve its delivery, we coupled GAA to polymer nanocarriers (NCs; ∼180 nm) coated with an antibody specific to ICAM-1. Fluorescence microscopy showed specific targeting of anti-ICAM/GAA NCs to cells, with efficient internalization and lysosomal transport, enhancing glycogen degradation over nontargeted GAA. Radioisotope tracing in mice demonstrated enhanced GAA accumulation in all organs, including Pompe targets. Along with improved delivery of Niemann-Pick and Fabry enzymes, previously described, these results indicate that ICAM-1 targeting holds promise as a broad platform for lysosomal enzyme delivery.

FROM THE CLINICAL EDITOR: In this study, ICAM-1 targeted nanocarriers were used to deliver GAA (acid alpha glucosidase) into cells to address the specific enzyme deficiency in Pompe's disease. The results unequivocally demonstrate enhanced enzyme delivery over nontargeted GAA in a mice model.

DOI10.1016/j.nano.2011.08.014
Alternate JournalNanomedicine
PubMed ID21906578
PubMed Central IDPMC3279604
Grant ListR01 HL098416 / HL / NHLBI NIH HHS / United States
R01 HL098416-01 / HL / NHLBI NIH HHS / United States
R01HL098416 / HL / NHLBI NIH HHS / United States