Document Detail


Programmable nanoparticle functionalization for in vivo targeting.
MedLine Citation:
PMID:  23047896     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The emerging demand for programmable functionalization of existing base nanocarriers necessitates development of an efficient approach for cargo loading that avoids nanoparticle redesign for each individual application. Herein, we demonstrate in vivo a postformulation strategy for lipidic nanocarrier functionalization with the use of a linker peptide, which rapidly and stably integrates cargos into lipidic membranes of nanocarriers after simple mixing through a self-assembling process. We exemplified this strategy by generating a VCAM-1-targeted perfluorocarbon nanoparticle for in vivo targeting in atherosclerosis (ApoE-deficient) and breast cancer (STAT-1-deficient) models. In the atherosclerotic model, a 4.1-fold augmentation in binding to affected aortas was observed for targeted vs. nontargeted nanoparticles (P<0.0298). Likewise, in the breast cancer model, a 4.9-fold increase in the nanoparticle signal from tumor vasculature was observed for targeted vs. nontargeted nanoparticles (P<0.0216). In each case, the nanoparticle was registered with fluorine ((19)F) magnetic resonance spectroscopy of the nanoparticle perfluorocarbon core, yielding a quantitative estimate of the number of tissue-bound nanoparticles. Because other common nanocarriers with lipid coatings (e.g., liposomes, micelles, etc.) can employ this strategy, this peptide linker postformulation approach is applicable to more than half of the available nanosystems currently in clinical trials or clinical uses.
Authors:
Hua Pan; Jacob W Myerson; Lingzhi Hu; Jon N Marsh; Kirk Hou; Michael J Scott; John S Allen; Grace Hu; Susana San Roman; Gregory M Lanza; Robert D Schreiber; Paul H Schlesinger; Samuel A Wickline
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-10-09
Journal Detail:
Title:  FASEB journal : official publication of the Federation of American Societies for Experimental Biology     Volume:  27     ISSN:  1530-6860     ISO Abbreviation:  FASEB J.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-01-03     Completed Date:  2013-03-07     Revised Date:  2014-01-09    
Medline Journal Info:
Nlm Unique ID:  8804484     Medline TA:  FASEB J     Country:  United States    
Other Details:
Languages:  eng     Pagination:  255-64     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Breast Neoplasms / metabolism,  pathology
Circular Dichroism
Disease Models, Animal
Humans
Mice
Nanoparticles*
Spectrometry, Fluorescence
Vascular Cell Adhesion Molecule-1 / metabolism
Grant Support
ID/Acronym/Agency:
CA-119342/CA/NCI NIH HHS; HL-073646/HL/NHLBI NIH HHS; R01 AR056223/AR/NIAMS NIH HHS; R01 CA043059/CA/NCI NIH HHS; R01 HL073646/HL/NHLBI NIH HHS; U54 CA119342/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Vascular Cell Adhesion Molecule-1
Comments/Corrections

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