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|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|
|Citation:||Advanced Healthcare Materials, 2015; 4(5):771-781|
|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|
|Appears in Collections:||Chemical Engineering publications|
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