Proximity-activated nanoparticles: in vitro performance of specific structural modification by enzymatic cleavage

R Adam Smith, Sarah L Sewell, Todd D GiorgioDepartment of Biomedical Engineering, Vanderbilt University, Nashville, TN, USAAbstract: The development and in vitro performance of a modular nanoscale system capable of specific structural modification by enzymatic activity is described in this work. Due...

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Autores principales:	R Adam Smith, Sarah L Sewell, Todd D Giorgio
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2008
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/842919dd564243ce8423f2aeb504bad0
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spelling	oai:doaj.org-article:842919dd564243ce8423f2aeb504bad02021-12-02T07:45:06ZProximity-activated nanoparticles: in vitro performance of specific structural modification by enzymatic cleavage1176-91141178-2013https://doaj.org/article/842919dd564243ce8423f2aeb504bad02008-03-01T00:00:00Zhttp://www.dovepress.com/proximity-activated-nanoparticles-in-vitro-performance-of-specific-str-a743https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013R Adam Smith, Sarah L Sewell, Todd D GiorgioDepartment of Biomedical Engineering, Vanderbilt University, Nashville, TN, USAAbstract: The development and in vitro performance of a modular nanoscale system capable of specific structural modification by enzymatic activity is described in this work. Due to its small physical size and adaptable characteristics, this system has the potential for utilization in targeted delivery systems and biosensing. Nanoparticle probes were synthesized containing two distinct fluorescent species including a quantum dot base particle and fluorescently labeled cleavable peptide substrate. Activity of these probes was monitored by gel electrophoresis with quantitative cleavage measurements made by fluorometric analysis. The model proximity-activated nanoparticles studied here exhibit significant susceptibility to cleavage by matrix metalloprotease-7 (MMP-7) at physiologically relevant concentrations, with nearly complete cleavage of available substrate molecules after 24 hours. This response is specific to MMP-7 enzyme activity, as cleavage is completely inhibited with the addition of EDTA. Utilization of enzyme-specific modification is a sensitive approach with broad applications for targeted therapeutics and biosensing. The versatility of this nanoparticle system is highlighted in its modular design, as it has the capability to integrate characteristics for detection, biosensing, targeting, and payload delivery into a single, multifunctional nanoparticle structure.Keywords: quantum dot, MMP-7, protease, proximity activated nanoparticle R Adam SmithSarah L SewellTodd D GiorgioDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2008, Iss Issue 1, Pp 95-103 (2008)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 R Adam Smith Sarah L Sewell Todd D Giorgio Proximity-activated nanoparticles: in vitro performance of specific structural modification by enzymatic cleavage
description	R Adam Smith, Sarah L Sewell, Todd D GiorgioDepartment of Biomedical Engineering, Vanderbilt University, Nashville, TN, USAAbstract: The development and in vitro performance of a modular nanoscale system capable of specific structural modification by enzymatic activity is described in this work. Due to its small physical size and adaptable characteristics, this system has the potential for utilization in targeted delivery systems and biosensing. Nanoparticle probes were synthesized containing two distinct fluorescent species including a quantum dot base particle and fluorescently labeled cleavable peptide substrate. Activity of these probes was monitored by gel electrophoresis with quantitative cleavage measurements made by fluorometric analysis. The model proximity-activated nanoparticles studied here exhibit significant susceptibility to cleavage by matrix metalloprotease-7 (MMP-7) at physiologically relevant concentrations, with nearly complete cleavage of available substrate molecules after 24 hours. This response is specific to MMP-7 enzyme activity, as cleavage is completely inhibited with the addition of EDTA. Utilization of enzyme-specific modification is a sensitive approach with broad applications for targeted therapeutics and biosensing. The versatility of this nanoparticle system is highlighted in its modular design, as it has the capability to integrate characteristics for detection, biosensing, targeting, and payload delivery into a single, multifunctional nanoparticle structure.Keywords: quantum dot, MMP-7, protease, proximity activated nanoparticle
format	article
author	R Adam Smith Sarah L Sewell Todd D Giorgio
author_facet	R Adam Smith Sarah L Sewell Todd D Giorgio
author_sort	R Adam Smith
title	Proximity-activated nanoparticles: in vitro performance of specific structural modification by enzymatic cleavage
title_short	Proximity-activated nanoparticles: in vitro performance of specific structural modification by enzymatic cleavage
title_full	Proximity-activated nanoparticles: in vitro performance of specific structural modification by enzymatic cleavage
title_fullStr	Proximity-activated nanoparticles: in vitro performance of specific structural modification by enzymatic cleavage
title_full_unstemmed	Proximity-activated nanoparticles: in vitro performance of specific structural modification by enzymatic cleavage
title_sort	proximity-activated nanoparticles: in vitro performance of specific structural modification by enzymatic cleavage
publisher	Dove Medical Press
publishDate	2008
url	https://doaj.org/article/842919dd564243ce8423f2aeb504bad0
work_keys_str_mv	AT radamsmith proximityactivatednanoparticlesinvitroperformanceofspecificstructuralmodificationbyenzymaticcleavage AT sarahlsewell proximityactivatednanoparticlesinvitroperformanceofspecificstructuralmodificationbyenzymaticcleavage AT todddgiorgio proximityactivatednanoparticlesinvitroperformanceofspecificstructuralmodificationbyenzymaticcleavage
_version_	1718399233041629184

Proximity-activated nanoparticles: in vitro performance of specific structural modification by enzymatic cleavage

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