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• W2024016899 abstract "Coupling therapeutic proteins to targeted nanocarriers can enhance their biodistribution. This is the case for enzyme replacement therapies where intravenously injected enzymes must avoid prolonged blood exposure while reaching body organs. We have shown enhanced tissue targeting of various lysosomal enzymes by coupling to nanocarriers targeted to intercellular adhesion molecule-1 (ICAM-1). Here, we varied design parameters to modify tissue enzyme levels without affecting specific targeting and relative biodistribution. We coupled a-galactosidase (aGal; affected in Fabry disease) to model polymer nanocarriers and varied enzyme load (50 vs. 500 molecules/particle), anti-ICAM surface density (80 vs. 180 molecules/particle), and nanocarrier concentration (1.6 x 1013 vs. 2.4 x 1013 carriers/kg) to render three formulations (45, 449, 555 microg alphaGal/kg). Naked alpha Gal preferentially distributed in blood vs. organs, while nanocarriers shifted biodistribution from blood to tissues. Accumulation in brain, kidneys, heart, liver, lungs, and spleen did not vary among nanocarrier formulations, with enhanced specific tissue accumulation compared to naked aGal. The highest specificity was associated with lowest antibody density and nanocarrier concentration, but highest enzyme load; possibly because of synergistic enzyme affinity toward cell-surface markers. Variation of these parameters significantly increased absolute enzyme accumulation. This strategy may help optimize delivery of lysosomal enzyme replacement and, likely, other protein delivery approaches." @default.
• W2024016899 created "2016-06-24" @default.
• W2024016899 creator A5000819682 @default.
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• W2024016899 date "2014-02-01" @default.
• W2024016899 modified "2023-10-17" @default.
• W2024016899 title "Enhancing Biodistribution of Therapeutic Enzymes <i>In Vivo</i> by Modulating Surface Coating and Concentration of ICAM-1-Targeted Nanocarriers" @default.
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• W2024016899 doi "https://doi.org/10.1166/jbn.2014.1718" @default.
• W2024016899 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4000549" @default.
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