title: A pH-Responsive Hydrogel Based on a Tumor-Targeting Mesoporous Silica Nanocomposite for Sustained Cancer Labeling and Therapy.
abstract: A facile strategy is presented to synthesize hyaluronic acid (HA) and a fluorescein isothiocyanate (FITC)-conjugated mesoporous silica nanocomposite (MSN) with multiple functions of fluorescence, tumor-cell targeting, pH-triggered gelation, and enzyme-responsive drug release. This injectable nanocomposite is able to indicate the entire tumor location and provides a microenvironment with rich anticancer drugs in and around tumor tissue for a long time, to avoid recrudescence. In this design, the mesoporous silica serves as the drug container, the FITC serves as a fluorescent probe, and the anchored HA plays multiple roles as drug-release cap, tumor-targeting points, and responsive gel matrix. Owing to the specific affinity between the HA on MSNs and the CD44 antigen over-expressed on tumor cells, the MSNs can selectively attach to tumor cells. The nanocomposites then exploit the pH-responsive interactions (hydrogen bonds) among the HA to self-assemble in situ into a hydrogel around the tumor tissue. The resulting hydrogel gradually releases its payload (doxorubicin, anticancer drugs)-loaded MSNs upon HA degradation in the presence of hyaluronidase-1 (Hyal-1), followed by endocytosis and intracellular drug release. All these properties have distinct benefits for tumor treatment, demonstrating that this device is a promising candidate for oncotherapy applications.
authors.affiliation: School of Chemical Engineering and Technology, Shanxi Key Laboratory of Energy Chemical Process Intensification, Institute of Polymer Science in Chemical Engineering, Xi'an Jiao Tong University, Xi'an, 710049, China. chenx2015@xjtu.edu.cn.
authors.forename: Xin
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Prosthodontics, Peking University School and Hospital of Stomatology, Beijing, 100081, China.
authors.forename: Zhongning
authors.initials: Z
authors.lastname: Liu
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage / Q000494:pharmacology; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000008:administration & dosage / Q000737:chemistry* / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D017879:Isothiocyanates / Q000737:chemistry; D053761:Nanocomposites / Q000737:chemistry*; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D010316:Particle Size; D016062:Porosity; D012822:Silicon Dioxide / Q000737:chemistry*; D013329:Structure-Activity Relationship; D013499:Surface Properties
chemical_list: D000970:Antineoplastic Agents; D017879:Isothiocyanates; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D012822:Silicon Dioxide; D004317:Doxorubicin; D006820:Hyaluronic Acid
keywords: biodegradable hydrogels; mesoporous silica nanocomposites; pH responsiveness; sustained cancer labeling and therapy; tumor-targeting