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https://hdl.handle.net/2440/100883
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Type: | Journal article |
Title: | γ-PGA-coated mesoporous silica nanoparticles with covalently attached prodrugs for enhanced cellular uptake and intracellular GSH-responsive release |
Other Titles: | Gamma-PGA-coated mesoporous silica nanoparticles with covalently attached prodrugs for enhanced cellular uptake and intracellular GSH-responsive release |
Author: | Du, X. Xiong, L. Dai, S. Qiao, S. |
Citation: | Advanced Healthcare Materials, 2015; 4(5):771-781 |
Publisher: | Wiley |
Issue Date: | 2015 |
ISSN: | 2192-2640 2192-2659 |
Statement of Responsibility: | Xin Du, Lin Xiong, Sheng Dai, and Shi Zhang Qiao |
Abstract: | Poor cellular uptake of drug delivery carriers and uncontrolled drug release remain to be the major obstacles in cancer therapy due to their low delivery efficiency. In this study, a multifunctional intracellular GSH (glutathione)-responsive silica-based drug delivery system with enhanced cellular uptake capability is developed. Uniform 50 nm colloidal mesoporous silica nanoparticles (MSNs) with mercaptopropyl-functionalized core and silanol-contained silica surface (MSNs-SHin ) are designed and fabricated as a platform for drug covalent attachment and particle surface modification. Doxorubicin (DOX) with primary amine group as an anticancer model drug is covalently conjugated to the mesopores of MSNs-SHin via disulfide bonds in the presence of a heterobifunctional linker (N-Succinimidyl 3-(2-pyridyldithio) propionate). Poly(γ-glutamic acid) (γ-PGA) can be coated onto the particle surface by sequential electrostatic adsorption of polyethyleneimine (PEI) and γ-PGA. The constructed delivery system exhibits enhanced cellular uptake via a speculated γ-glutamyl transpeptidase (GGT)-mediated endocytosis pathway and controlled drug release capacity via intracellular GSH-responsive disulfide-bond cleavage, and thus significantly inhibits the growth of cancer cells. The multifunctional delivery system paves a new way for developing high-efficient particle-based nanotherapeutic approach for cancer treatment. |
Keywords: | disulfide bonds; doxorubicin; enhanced cellular uptake; GSH-responsive release; γ-PGA surface coating; mesoporous silica nanoparticles |
Rights: | © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim |
DOI: | 10.1002/adhm.201400726 |
Grant ID: | http://purl.org/au-research/grants/arc/DP140104062 http://purl.org/au-research/grants/arc/DP130104459 |
Published version: | http://dx.doi.org/10.1002/adhm.201400726 |
Appears in Collections: | Aurora harvest 3 Chemical Engineering publications |
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