title: Multifunctional nanosheets based on folic acid modified manganese oxide for tumor-targeting theranostic application.
abstract: It is highly desirable to develop smart nanocarriers with stimuli-responsive drug-releasing and diagnostic-imaging functions for cancer theranostics. Herein, we develop a reduction and pH dual-responsive tumor theranostic platform based on degradable manganese dioxide (MnO2) nanosheets. The MnO2 nanosheets with a size of 20-60 nm were first synthesized and modified with (3-Aminopropyl) trimethoxysilane (APTMS) to get amine-functionalized MnO2, and then functionalized by NH2-PEG2000-COOH (PEG). The tumor-targeting group, folic acid (FA), was finally conjugated with the PEGylated MnO2 nanosheets. Then, doxorubicin (DOX), a chemotherapeutic agent, was loaded onto the modified nanosheets through a physical adsorption, which was designated as MnO2-PEG-FA/DOX. The prepared MnO2-PEG-FA/DOX nanosheets with good biocompatibility can not only efficiently deliver DOX to tumor cells in vitro and in vivo, leading to enhanced anti-tumor efficiency, but can also respond to a slightly acidic environment and high concentration of reduced glutathione (GSH), which caused degradation of MnO2 into manganese ions enabling magnetic resonance imaging (MRI). The longitudinal relaxation rate r1 was 2.26 mM(-1) s(-1) at pH 5.0 containing 2 mM GSH. These reduction and pH dual-responsive biodegradable nanosheets combining efficient MRI and chemotherapy provide a novel and promising platform for tumor-targeting theranostic application.
authors.affiliation: School of Pharmaceutical Sciences, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, Henan Province 450001, People's Republic of China.
authors.forename: Yongwei
authors.initials: Y
authors.lastname: Hao
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.forename: Bingxiang
authors.initials: B
authors.lastname: Zhang
authors.forename: Hongjuan
authors.initials: H
authors.lastname: Zhao
authors.forename: Mengya
authors.initials: M
authors.lastname: Niu
authors.forename: Yujie
authors.initials: Y
authors.lastname: Hu
authors.forename: Cuixia
authors.initials: C
authors.lastname: Zheng
authors.forename: Hongling
authors.initials: H
authors.lastname: Zhang
authors.forename: Junbiao
authors.initials: J
authors.lastname: Chang
authors.forename: Zhenzhong
authors.initials: Z
authors.lastname: Zhang
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D016503:Drug Delivery Systems; D005492:Folic Acid / Q000008:administration & dosage* / Q000737:chemistry; D006367:HeLa Cells; D006801:Humans; D017895:Manganese Compounds / Q000737:chemistry*; D057145:Nanoshells / Q000737:chemistry; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D010087:Oxides / Q000737:chemistry*; D010316:Particle Size; D000068936:Theranostic Nanomedicine / Q000379:methods*; D016896:Treatment Outcome; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D017895:Manganese Compounds; D010087:Oxides; C027424:manganese oxide; D004317:Doxorubicin; D005492:Folic Acid