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

Department of Biomedical Engineering, Vanderbilt University, Nashville, TN 37235, USA.
International Journal of Nanomedicine (Impact Factor: 4.38). 02/2008; 3(1):95-103.
Source: PubMed


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.

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    • "The experiment results proved that MMP-2/9 can cleave the ACPP and the scissor rate of ACPP-DOX was related to the concentration of MMP-2/9. MMP concentration was obviously related to the degree of cleavage; more cleavage was also found in MMP-activated imaging nanoparticles with the increase of extra MMPs.28 In our previous experiments, the hydrolysis fragments of ACPP have been detected by MALDI-TOF-MS and it was proved that the ACPP could be cleaved by MMP-2/9 at target site.29 "
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