title: Hybrid lipid-capped mesoporous silica for stimuli-responsive drug release and overcoming multidrug resistance.
abstract: 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.
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University , 103 Wenhua Road, Shenyang, Liaoning Province 110016, P. R. China.
authors.forename: Ning
authors.initials: N
authors.lastname: Han
authors.forename: Qinfu
authors.initials: Q
authors.lastname: Zhao
authors.forename: Long
authors.initials: L
authors.lastname: Wan
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.forename: Yikun
authors.initials: Y
authors.lastname: Gao
authors.forename: Pu
authors.initials: P
authors.lastname: Wang
authors.forename: Zhanyou
authors.initials: Z
authors.lastname: Wang
authors.forename: Jinghai
authors.initials: J
authors.lastname: Zhang
authors.forename: Tongying
authors.initials: T
authors.lastname: Jiang
authors.forename: Siling
authors.initials: S
authors.lastname: Wang
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000737:chemistry; D002470:Cell Survival / Q000187:drug effects; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000737:chemistry*; D004058:Diffusion; D004317:Doxorubicin / Q000008:administration & dosage* / Q000737:chemistry; D018432:Drug Resistance, Multiple; D006801:Humans; D061986:MCF-7 Cells; D053769:Nanocapsules / Q000737:chemistry* / Q000648:ultrastructure; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry; D016062:Porosity; D012822:Silicon Dioxide / Q000737:chemistry*; D024505:Tocopherols / Q000737:chemistry*
chemical_list: D000903:Antibiotics, Antineoplastic; D003692:Delayed-Action Preparations; D053769:Nanocapsules; D011092:Polyethylene Glycols; D012822:Silicon Dioxide; D004317:Doxorubicin; D024505:Tocopherols; C000595209:polyethylene glycol 1000
keywords: drug delivery; lipid; mesoporous silica; multidrug resistance; polymer; stimuli-responsive release