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Protamine-Capped Mesoporous Silica Nanoparticles for Biologically Triggered Drug Release
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.
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Metadata
- Authors
- Radhakrishnan, K., Gupta, S., Gnanadhas, D. P., Ramamurthy, P. C., Chakravortty, D., & Raichur, A. M.
- Affiliations
- Indian Institute of Science Bangalore (IN)
- Department of Microbiology and Cell Biology Indian Institute of Science Bangalore 560012 India
- University of Johannesburg (ZA)
- Corresponding author
- Raichur, Ashok M.
- ORCID
- Venue
- Particle & Particle Systems Characterization
- Publisher
- Wiley
- Published
- 2013-10-22
- Volume
- 31
- Issue
- 4
- Pages
- 449-458
- ISSN
- 0934-0866 (ISSN-L)
- 1521-4117
- OpenAlex
- W1998103515
- Cited by
- 50
- References
- 41
- Citations by year
- 2024: 3 · 2023: 4 · 2022: 5 · 2021: 9 · 2020: 4 · 2019: 4 · 2018: 4 · 2017: 2 · 2016: 4 · 2015: 9 · 2014: 2
- FWCI
- 1.69
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Particle & Particle Systems Characterization (publishedVersion)
- NOT FOUND REPOSITORY (Indian Institute of Science Bangalore) (submittedVersion)
- Topics
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Physical Sciences › Materials Science › Materials Chemistry › Mesoporous Materials and Catalysis
- Physical Sciences › Earth and Planetary Sciences › Geochemistry and Petrology › Clay minerals and soil interactions
- Keywords
- mesoporous silica nanoparticles, protamine, enzyme-responsive drug release, trypsin, colorectal cancer, anticancer drug delivery, hydrophobic drug encapsulation, cancer cell death, biocompatibility
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