title: Mesoporous manganese silicate coated silica nanoparticles as multi-stimuli-responsive T1-MRI contrast agents and drug delivery carriers.
abstract: A novel kind of monodisperse mesoporous manganese silicate coated silica nanoparticle (MMSSN) as a highly efficient T1-weighted MRI contrast agent (CA) and drug carrier for cancer diagnosis and chemotherapy has been constructed by a modified "SiO2 sacrifice and in situ silicate growth" approach under a relatively low hydrothermal temperature and alkali-free condition. The mesoporous manganese silicate shell provides a large specific surface area and abundant exposed Mn paramagnetic centers to water molecules, which endows the MMSSNs with extraordinarily high longitudinal relaxivity. Meanwhile, the MMSSNs presented an efficient pH/redox-responsive T1-MRI feature based on the significant enhancement of relaxation rate (r1) stimulated by mild acidic environment or reducing agent (GSH) both in vitro and in vivo. Furthermore, the mesoporous structure and negatively charged pore surface of the manganese silicate shell enable the MMSSNs to attain anti-cancer drug (DOX) storage and a pH-responsive release, which is suitable for on-demand drug release for the chemotherapy of tumors. Therefore, the mesoporous manganese silicate-based nanomaterial is a promising candidate as T1-MRI CAs and anticancer-drug delivery carriers for the theranostics of tumor in an intelligent and on-demand manner.
  
  
  CONCLUSIONS
  MRI is one of the most frequently used imaging techniques in daily clinics for cancer diagnosis. Using contrast agents (CAs) in MRI can afford much clearer and enlarged images of detectable organs. Gadolinium (Gd(3+))-based T1-positive CAs are widely used but associated with the risk of nephrogenic systemic fibrosis. To achieve much safer CAs, various Mn(2+)-based T1-positive CAs have been reported, such as MnO or core-shell MnOx-based nanoparticles. However, the efficiency of these CAs is still lower. Herein, we report a novel kind of mesoporous manganese silicate coated silica nanoparticle as CA and anti-cancer drug carrier. Results obtained from this study, especially the pH/redox-responsive T1-MRI feature are helpful for us to further design efficient MnSiO3-based materials for clinical MRI applications.
authors.affiliation: Key Laboratory for Ultrafine Materials of Ministry of Education, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai 200237, China.
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Li
authors.affiliation: Key Laboratory for Ultrafine Materials of Ministry of Education, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai 200237, China. Electronic address: wenruru@ecust.edu.cn.
authors.forename: Wenru
authors.initials: W
authors.lastname: Zhao
authors.affiliation: Department of Radiology, Shanghai Cancer Center, Fudan University, Shanghai 200032, China.
authors.forename: Xiaohang
authors.initials: X
authors.lastname: Liu
authors.affiliation: Key Laboratory for Ultrafine Materials of Ministry of Education, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai 200237, China.
authors.forename: Kaiqiang
authors.initials: K
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China.
authors.forename: Shaojia
authors.initials: S
authors.lastname: Zhu
authors.affiliation: State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Shi
authors.affiliation: State Key Lab of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Science, Shanghai 200050, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Key Laboratory for Ultrafine Materials of Ministry of Education, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai 200237, China; State Key Lab of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Science, Shanghai 200050, China. Electronic address: jlshi@mail.sic.ac.cn.
authors.forename: Jianlin
authors.initials: J
authors.lastname: Shi
mesh_terms: D000818:Animals; D020099:Coated Materials, Biocompatible / Q000737:chemistry / Q000494:pharmacology; D003287:Contrast Media / Q000737:chemistry / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry / Q000494:pharmacology; D005260:Female; D056945:Hep G2 Cells; D006801:Humans; D061986:MCF-7 Cells; D008279:Magnetic Resonance Imaging; D017895:Manganese Compounds / Q000737:chemistry / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000737:chemistry*; D016716:PC12 Cells; D016062:Porosity; D051381:Rats; D017640:Silicates / Q000737:chemistry / Q000494:pharmacology; D012822:Silicon Dioxide / Q000737:chemistry / Q000494:pharmacology
chemical_list: D020099:Coated Materials, Biocompatible; D003287:Contrast Media; D004337:Drug Carriers; D017895:Manganese Compounds; D017640:Silicates; D012822:Silicon Dioxide
keywords: Contrast agents; Drug delivery; Manganese silicate; Stimuli-responsive; T(1)-weighted MRI