Hybrid Lipid-Capped Mesoporous Silica for Stimuli-Responsive Drug Release and Overcoming Multidrug Resistance
journal contributionposted on 11.02.2015, 00:00 by Ning Han, Qinfu Zhao, Long Wan, Ying Wang, Yikun Gao, Pu Wang, Zhanyou Wang, Jinghai Zhang, Tongying Jiang, Siling Wang
Multidrug resistance (MDR) is known to be a great obstruction to successful chemotherapy, and considerable efforts have been devoted to reverse MDR including designing various functional drug delivery systems. In this study, hybrid lipid-capped mesoporous silica nanoparticles (LTMSNs), aimed toward achieving stimuli-responsive drug release to circumvent MDR, were specially designated for drug delivery. After modifying MSNs with hydrophobic chains through disulfide bond on the surface, lipid molecules composing polymer d-α-tocopherol polyethylene glycol 1000 succinate (TPGS) with molar ratio of 5:1 were subsequently added to self-assemble into a surrounded lipid layer via hydrophobic interaction acting as smart valves to block the pore channels of carrier. The obtained LTMSNs had a narrow size distribution of ca. 190 nm and can be stably dispersed in body fluids, which may ensure a long circulating time and ideal enhanced permeability and retention effect. Doxorubicin (DOX) was chosen as a model drug to be encapsulated into LTMSNs. Results showed that this hybrid lipid-capped mesoporous silica drug delivery system can achieve redox and pH-responsive release of DOX, thereby avoiding the premature leakage of drug before reaching the specific site and releasing DOX within the cancerous cells. Owing to the presence of TPGS-containing lipid layer, LTMSNs–DOX exhibited higher uptake efficiency, cytotoxicity, and increased intracellular accumulation in resistant MCF-7/Adr cells compared with DOX solution, proving to be a promising vehicle to realize intracellular drug release and inhibit drug efflux.
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model drugdisulfide bondLTMSNintracellular drug releasepore channelsbody fluidslipid moleculesDOX solutionOvercoming Multidrug ResistanceMultidrug resistancedrug effluxuptake efficiencyMDRretention effectlipid layerMSNintracellular accumulationsize distribution190 nmdrug delivery systemsTPGSmolar ratioMCFdrug delivery