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Nanomedicine. 2010 Apr;6(2):334-43. doi: 10.1016/j.nano.2009.09.001. Epub 2009 Oct 2.

Ligand-modified gene carriers increased uptake in target cells but reduced DNA release and transfection efficiency.

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  • 1Department of Biomedical Engineering, Yale University, New Haven, Connecticut 06511, USA.

Abstract

DNA delivery to cells can be improved by using particle carriers made from biodegradable polymers such as poly(lactic-co-glycolic)acid (PLGA). It is speculated that addition of targeting moieties to the particle surface to facilitate uptake can further enhance gene expression in specific cells or tissues. Taking advantage of well-known receptor/ligand interactions in intestinal and renal epithelial cells, we formulated PLGA particles with high density of surface-bound bovine serum albumin (BSA; approximately 768 molecules/particle). BSA-coated particles exhibited significantly higher uptake by cells expressing the albumin receptor, megalin, and resisted degradation in low pH. However, gene expression from BSA-coated particles was 3- to 10-fold lower than that from unmodified particles; this reduction in transfection efficiency was probably due to the slower DNA release rate from modified particles. In this setting, addition of a targeting feature to particles reduced their effectiveness. Our study highlights the importance of the interplay between cell uptake and payload release in the design of polymer drug carriers.

FROM THE CLINICAL EDITOR:

DNA delivery to cells can be improved by using particle carriers such as PLGA. Taking advantage of known receptor/ligand interactions in intestinal and renal epithelial cells, PLGA particles with high density surface-bound BSA were formulated. BSA-coated particles exhibited significantly higher uptake; however, gene expression was 3 to 10-fold lower. Unexpectedly, the addition of a targeting feature to these particles reduced their overall effectiveness.

PMID:
19800989
PMCID:
PMC2847641
[PubMed - indexed for MEDLINE]
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