PMID- 19800989
OWN - NLM
STAT- MEDLINE
DCOM- 20100630
LR  - 20220309
IS  - 1549-9642 (Electronic)
IS  - 1549-9634 (Print)
IS  - 1549-9634 (Linking)
VI  - 6
IP  - 2
DP  - 2010 Apr
TI  - Ligand-modified gene carriers increased uptake in target cells but reduced DNA 
      release and transfection efficiency.
PG  - 334-43
LID - 10.1016/j.nano.2009.09.001 [doi]
AB  - 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.
CI  - Copyright 2010 Elsevier Inc. All rights reserved.
FAU - Cu, Yen
AU  - Cu Y
AD  - Department of Biomedical Engineering, Yale University, New Haven, Connecticut 
      06511, USA.
FAU - LeMoellic, Cathy
AU  - LeMoellic C
FAU - Caplan, Michael J
AU  - Caplan MJ
FAU - Saltzman, W Mark
AU  - Saltzman WM
LA  - eng
GR  - R01 EB000487-18A2/EB/NIBIB NIH HHS/United States
GR  - R01 EB000487-15/EB/NIBIB NIH HHS/United States
GR  - EB000487/EB/NIBIB NIH HHS/United States
GR  - R01 EB000487-17/EB/NIBIB NIH HHS/United States
GR  - R01 EB000487/EB/NIBIB NIH HHS/United States
GR  - R56 EB000487/EB/NIBIB NIH HHS/United States
GR  - R01 EB000487-16/EB/NIBIB NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20091002
PL  - United States
TA  - Nanomedicine
JT  - Nanomedicine : nanotechnology, biology, and medicine
JID - 101233142
RN  - 0 (Drug Carriers)
RN  - 0 (Ligands)
RN  - 9007-49-2 (DNA)
SB  - IM
MH  - Animals
MH  - Cells, Cultured
MH  - DNA/*administration & dosage/*pharmacokinetics
MH  - Drug Carriers/*chemistry
MH  - Kidney/*chemistry/*physiology
MH  - Ligands
MH  - Opossums
MH  - Transfection/*methods
PMC - PMC2847641
MID - NIHMS150435
COIS- The authors declare no conflict of interest
EDAT- 2009/10/06 06:00
MHDA- 2010/07/01 06:00
PMCR- 2011/04/01
CRDT- 2009/10/06 06:00
PHST- 2009/03/01 00:00 [received]
PHST- 2009/08/27 00:00 [revised]
PHST- 2009/09/03 00:00 [accepted]
PHST- 2009/10/06 06:00 [entrez]
PHST- 2009/10/06 06:00 [pubmed]
PHST- 2010/07/01 06:00 [medline]
PHST- 2011/04/01 00:00 [pmc-release]
AID - S1549-9634(09)00184-1 [pii]
AID - 10.1016/j.nano.2009.09.001 [doi]
PST - ppublish
SO  - Nanomedicine. 2010 Apr;6(2):334-43. doi: 10.1016/j.nano.2009.09.001. Epub 2009 
      Oct 2.