title: A Hyaluronidase-Responsive Nanoparticle-Based Drug Delivery System for Targeting Colon Cancer Cells.
abstract: The ability of nanoparticles to target tumors and to enable site-specific drug release provides a unique system for the delivery of effective therapy with reduced toxic side effects. In this study, we used mesoporous silica nanoparticles (MSN) to fabricate a targeted drug delivery system that is responsive to hyaluronidase (HAase). Following engraftment of desthiobiotin onto the surface of MSN, a streptavidin complex was generated, which was functionalized with biotin-modified hyaluronic acid (HA) to enable controlled drug release at cancer cells expressing HAase. Various technologies were used to confirm the successful fabrication of this MSN-based nanocarrier system for targeted drug delivery. In vitro analyses showed that the release of doxorubicin hydrochloride (Dox) was accelerated significantly in the presence of biotin or HAase and accelerated further in the presence of biotin and HAase. Uptake by cancer cells was mediated efficiently by CD44 receptor-mediated endocytosis and the MSN exhibited good biocompatibility in vitro and in vivo MSN-HA/Dox nanoparticles induced apoptosis in cancer cells more efficiently than free doxorubicin and inhibited tumor growth with minimal systemic toxicity in vivo Collectively, our findings offered a preclinical proof of concept for a novel targeted drug delivery carrier system for cancer therapy. Cancer Res; 76(24); 7208-18. ©2016 AACR.
authors.affiliation: Institute for Biomedical Sciences, Georgia State University, Atlanta, Georgia. mzhang21@gsu.edu.|Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, Georgia.
authors.forename: Mingzhen
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Institute for Biomedical Sciences, Georgia State University, Atlanta, Georgia.|Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, Georgia.|The 2nd Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, P.R. China.
authors.forename: Changlong
authors.initials: C
authors.lastname: Xu
authors.affiliation: Department of Chemistry, Georgia State University, Atlanta, Georgia.
authors.forename: Liuqing
authors.initials: L
authors.lastname: Wen
authors.affiliation: Institute for Biomedical Sciences, Georgia State University, Atlanta, Georgia.|Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, Georgia.
authors.forename: Moon Kwon
authors.initials: MK
authors.lastname: Han
authors.affiliation: Institute for Biomedical Sciences, Georgia State University, Atlanta, Georgia.|Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, Georgia.
authors.forename: Bo
authors.initials: B
authors.lastname: Xiao
authors.affiliation: Department of Chemistry, Georgia State University, Atlanta, Georgia.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Institute for Biomedical Sciences, Georgia State University, Atlanta, Georgia.|Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, Georgia.
authors.forename: Yuchen
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Institute for Biomedical Sciences, Georgia State University, Atlanta, Georgia.|Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, Georgia.
authors.forename: Zhan
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Institute for Biomedical Sciences, Georgia State University, Atlanta, Georgia.|Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, Georgia.
authors.forename: Emilie
authors.initials: E
authors.lastname: Viennois
authors.affiliation: Institute for Biomedical Sciences, Georgia State University, Atlanta, Georgia.|Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, Georgia.|Veterans Affairs Medical Center, Decatur, Georgia.
authors.forename: Didier
authors.initials: D
authors.lastname: Merlin
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D004317:Doxorubicin / Q000008:administration & dosage*; D016503:Drug Delivery Systems / Q000379:methods*; D065546:Drug Liberation; D006801:Humans; D006821:Hyaluronoglucosaminidase; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D058726:Nanoconjugates; D012822:Silicon Dioxide; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D058726:Nanoconjugates; D012822:Silicon Dioxide; D004317:Doxorubicin; D006821:Hyaluronoglucosaminidase