title: Dual-stimuli responsive hyaluronic acid-conjugated mesoporous silica for targeted delivery to CD44-overexpressing cancer cells.
abstract: In this paper, a redox and enzyme dual-stimuli responsive delivery system (MSN-SS-HA) based on mesoporous silica nanoparticles (MSN) for targeted drug delivery has been developed, in which hyaluronic acid (HA) was conjugated on the surface of silica by cleavable disulfide (SS) bonds. HA possesses many attractive features, including acting as a targeting ligand and simultaneously a capping agent to achieve targeted and controlled drug release, prolonging the blood circulation time, and increasing the physiological stability and biocompatibility of MSN. The anticancer drug doxorubicin (DOX) was chosen as a model drug. In vitro drug release profiles showed that the release of DOX was markedly restricted in pH 7.4 and pH 5.0 phosphate buffer solution (PBS), while it was significantly accelerated upon the addition of glutathione (GSH)/hyaluronidases (HAase). In addition, the release was further accelerated in the presence of both GSH and HAase. Confocal laser scanning microscopy (CLSM) and fluorescence-activated cell sorting (FACS) showed that MSN-SS-HA exhibited a higher cellular uptake via cluster of differentiation antigen-44 (CD44) receptor-mediated endocytosis compared with thiol (SH)-functionalized MSN (MSN-SH) in CD44 receptor over-expressed in human HCT-116 cells. The DOX-loaded MSN-SS-HA was more cytotoxic against HCT-116 cells than NIH-3T3 (CD44 receptor-negative) cells due to the enhanced cellular uptake of MSN-SS-HA. This paper describes the development of an effective method for using a single substance as multi-functional material for MSN to simultaneously regulate drug release and achieve targeted delivery.
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, Liaoning Province 110016, China.
authors.forename: Qinfu
authors.initials: Q
authors.lastname: Zhao
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, Liaoning Province 110016, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Liu
authors.affiliation: Institute of Medicine, Qiqihar Medical University, Qiqihar 161006, China.
authors.forename: Wenquan
authors.initials: W
authors.lastname: Zhu
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, Liaoning Province 110016, China.
authors.forename: Changshan
authors.initials: C
authors.lastname: Sun
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, Liaoning Province 110016, China.
authors.forename: Donghua
authors.initials: D
authors.lastname: Di
authors.affiliation: School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: College of Life and Health Sciences, Northeastern University, Shenyang 110004, China.
authors.forename: Pu
authors.initials: P
authors.lastname: Wang
authors.affiliation: College of Life and Health Sciences, Northeastern University, Shenyang 110004, China.
authors.forename: Zhanyou
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, Liaoning Province 110016, China. Electronic address: silingwang@syphu.edu.cn.
authors.forename: Siling
authors.initials: S
authors.lastname: Wang
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003692:Delayed-Action Preparations / Q000008:administration & dosage* / Q000737:chemistry; D004058:Diffusion; D004317:Doxorubicin / Q000008:administration & dosage* / Q000737:chemistry; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism*; D006820:Hyaluronic Acid / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D051379:Mice; D053769:Nanocapsules / Q000737:chemistry / Q000648:ultrastructure; D058726:Nanoconjugates / Q000737:chemistry / Q000648:ultrastructure; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D010316:Particle Size; D016062:Porosity; D012822:Silicon Dioxide / Q000737:chemistry
chemical_list: C497483:CD44 protein, human; D003692:Delayed-Action Preparations; D018960:Hyaluronan Receptors; D053769:Nanocapsules; D058726:Nanoconjugates; D012822:Silicon Dioxide; D004317:Doxorubicin; D006820:Hyaluronic Acid
keywords: Disulfide bonds; Doxorubicin; Dual-stimuli responsive; Hyaluronic acid; Mesoporous silica nanoparticles