PMID- 21219848
OWN - NLM
STAT- MEDLINE
DCOM- 20110406
LR  - 20181201
IS  - 1090-2104 (Electronic)
IS  - 0006-291X (Linking)
VI  - 405
IP  - 2
DP  - 2011 Feb 11
TI  - 'IntraCell' plugin for assessment of intracellular localization of nano-delivery 
      systems and their targeting to the individual organelles.
PG  - 228-33
LID - 10.1016/j.bbrc.2011.01.015 [doi]
AB  - Efficient intracellular targeting of drugs and drug delivery systems (DDSs) is a 
      major challenge that should be overcome to enhance the therapeutic efficiency of 
      biopharmaceuticals and other intracellularly-acting drugs. Studies that 
      quantitatively assess the mechanisms, barriers, and efficiency of intracellular 
      drug delivery are required to determine the therapeutic potential of 
      intracellular targeting of nano-delivery systems. In this study we report 
      development and application of a novel 'IntraCell' plugin for ImageJ that is 
      useful for quantitative assessment of uptake and intracellular localization of 
      the drug/DDS and estimation of targeting efficiency. The developed plugin is 
      based on threshold-based identification of borders of cell and of the individual 
      organelles on confocal images and pixel-by-pixel analysis of fluorescence 
      intensities. We applied the developed 'IntraCell' plugin to investigate uptake 
      and intracellular targeting of novel endoplasmic reticulum (ER)-targeted delivery 
      system based on PLGA nanoparticles decorated with ER-targeting or control 
      peptides and encapsulating antigenic peptide and fluorescent marker. Decoration 
      of the nanoparticles with peptidic residues affected their uptake and 
      intracellular trafficking in HeLa cells, indicating that the targeting peptide 
      was identified as ER-targeting signal by the intracellular trafficking mechanisms 
      in HeLa cells and that these mechanisms can handle nano-DDS of the size 
      comparable to some intracellular vesicles (hundreds of nanometers in diameter). 
      We conclude that decoration of nanoparticles with peptidic residues affects their 
      intracellular localization and trafficking and can be potentially used for 
      intracellularly-targeted drug delivery. 'IntraCell' plugin is an useful tool for 
      quantitative assessment of efficiency of uptake and intracellular drug targeting. 
      In combination with other experimental approaches, it will be useful for the 
      development of intracellularly-targeted formulations with enhanced and controlled 
      drug pharmacological activities, such as delivery of antigenic peptides for 
      anticancer vaccination and for other applications.
CI  - Copyright (c) 2011 Elsevier Inc. All rights reserved.
FAU - Sneh-Edri, Hadas
AU  - Sneh-Edri H
AD  - Department of Pharmacology, Ben-Gurion University of the Negev, Beer-Sheva, 
      Israel.
FAU - Stepensky, David
AU  - Stepensky D
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110108
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 1SIA8062RS (Polylactic Acid-Polyglycolic Acid Copolymer)
RN  - 26009-03-0 (Polyglycolic Acid)
RN  - 33X04XA5AT (Lactic Acid)
SB  - IM
MH  - Biological Transport
MH  - *Drug Delivery Systems
MH  - HeLa Cells
MH  - Humans
MH  - Lactic Acid/chemistry
MH  - Nanoparticles/*chemistry
MH  - Organelles/metabolism
MH  - Polyglycolic Acid/chemistry
MH  - Polylactic Acid-Polyglycolic Acid Copolymer
EDAT- 2011/01/12 06:00
MHDA- 2011/04/07 06:00
CRDT- 2011/01/12 06:00
PHST- 2011/01/03 00:00 [received]
PHST- 2011/01/04 00:00 [accepted]
PHST- 2011/01/12 06:00 [entrez]
PHST- 2011/01/12 06:00 [pubmed]
PHST- 2011/04/07 06:00 [medline]
AID - S0006-291X(11)00025-8 [pii]
AID - 10.1016/j.bbrc.2011.01.015 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2011 Feb 11;405(2):228-33. doi: 
      10.1016/j.bbrc.2011.01.015. Epub 2011 Jan 8.