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Overcoming multidrug resistance of cancer cells by direct intranuclear drug delivery using TAT-conjugated mesoporous silica nanoparticles

Paper ID Volume ID Publish Year Pages File Format Full-Text
6295 476 2013 12 PDF Available
Title
Overcoming multidrug resistance of cancer cells by direct intranuclear drug delivery using TAT-conjugated mesoporous silica nanoparticles
Abstract

The development of multidrug resistance (MDR) in cancer cells is one of major obstacles to the effective cancer chemotherapy. In this report we demonstrate the effective circumvention of multidrug resistance in cancer cells by an active nuclear-targeted drug delivery system that was constructed by conjugating TAT peptide onto the surface of mesoporous silica nanoparticles (MSNs-TAT). The conjugation of TAT peptide facilitated the intranuclear localization of MSNs-TAT and the release of the encapsulated drugs directly within the nucleoplasm. The direct intranuclear drug delivery of doxorubicin (DOX) in multidrug resistant MCF-7/ADR cancer cells was capable of increasing the intracellular as well as intranuclear drug concentrations much more effectively than free DOX or delivered by MSNs in the absence of TAT peptide. With the nuclear drug delivery fashion, DOX-MSNs-TAT presents a promising strategy in overcoming MDR in cancer cells and improving the therapeutic index of currently available chemotherapeutics by enhancing therapeutic efficacy and reducing side effects.

Keywords
Nuclear-targeted; MSNs; TAT peptide; Multidrug resistance; DOX
First Page Preview
Overcoming multidrug resistance of cancer cells by direct intranuclear drug delivery using TAT-conjugated mesoporous silica nanoparticles
Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 34, Issue 11, April 2013, Pages 2719–2730
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering