Du, X.Xiong, L.Dai, S.Qiao, S.2016-09-012016-09-012015Advanced healthcare materials, 2015; 4(5):771-7812192-26402192-2659http://hdl.handle.net/2440/100883Poor 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.en© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheimdisulfide bonds; doxorubicin; enhanced cellular uptake; GSH-responsive release; γ-PGA surface coating; mesoporous silica nanoparticlesJournal article003002143110.1002/adhm.2014007260003526205000162-s2.0-849283536742-s2.0-84920982842168674Qiao, S. [0000-0002-1220-1761] [0000-0002-4568-8422]