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Protamine-Capped Mesoporous Silica Nanoparticles for Biologically Triggered Drug Release

Radhakrishnan, Krishna and Gupta, Satyajit and Gnanadhas, Divya Prakash and Ramamurthy, Praveen C and Chakravortty, Dipshika and Raichur, Ashok M (2014) Protamine-Capped Mesoporous Silica Nanoparticles for Biologically Triggered Drug Release. In: PARTICLE & PARTICLE SYSTEMS CHARACTERIZATION, 31 (4). pp. 449-458.

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Official URL: http://dx.doi.org/10.1002/ppsc.201300219

Abstract

The fabrication of a mesoporous silica nanoparticle (MSN)-protamine hybrid system (MSN-PRM) is reported that selectively releases drugs in the presence of specific enzyme triggers present in the proximity of cancer cells. The enzyme trigger involved is a protease called trypsin, which is overexpressed in certain specific pathological conditions, such as inflammation and cancer. Overexpression of trypsin is known to be associated with invasion, metastasis, and growth in several cancers, such as leukemia, colon cancer, and colorectal cancer. The current system (MSN-PRM) consists of an MSN support in which mesopores are capped with an FDA-approved peptide drug protamine, which effectively blocks the outward diffusion of the drug molecules from the mesopores of the MSNs. On exposure to the enzyme trigger, the protamine cap disintegrates, opening up the molecular gates and releasing the entrapped drug molecules. The system exhibits minimal premature release in the absence of the trigger and selectively releases the encapsulated drugs in the presence of the proteases secreted by colorectal cancer cells. The ability of the MSN-PRM particles to deliver anticancer drugs to colorectal cancer cells has also been demonstrated. The hydrophobic drug is released into cancer cells subsequent to disintegration of the protamine cap, resulting in cell death. Drug-induced cell death in colorectal cancer cells is significantly enhanced when the hydrophobic drug that is known to degrade in aqueous environments is encapsulated in the MSN-PRM system in comparison to the free drug (P < 0.05). The system, which shows good biocompatibility and selective drug release, is a promising platform for cancer specific drug delivery.

Item Type: Journal Article
Additional Information: Copyright for this article belongs to the WILEY-V C H VERLAG GMBH, GERMANY
Keywords: biocompatible; drug delivery; enzyme mediated; cancer; mesoporous
Department/Centre: Division of Biological Sciences > Microbiology & Cell Biology
Division of Mechanical Sciences > Materials Engineering (formerly Metallurgy)
Depositing User: Id for Latest eprints
Date Deposited: 03 Jun 2014 08:24
Last Modified: 03 Jun 2014 08:24
URI: http://eprints.iisc.ac.in/id/eprint/49079

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