title: Synthesis of mesoporous silica nanoparticle-oxaliplatin conjugates for improved anticancer drug delivery.
abstract: Mesoporous silica nanoparticles (MSN) with 1,2-bidentate carboxyl groups on the surface reacted with 1,2-diaminecyclohexano platinum(II) dinitrate (DACH-Pt-(NO3)2) which is an active anticancer species of clinic relevant oxaliplatin to form MSN-Pt. The modification of the parent particles was monitored by (13)C, (29)Si solid-state NMR, X-ray measurements (XRD) and Fourier transform infrared spectroscopy (FT-IR). After loading with platinum drugs, MSN-Pt exhibited two strong Pt4f signals as indicated by X-ray photoelectron spectroscopy (XPS). The platinum content in the conjugates was calculated to be 9.7% according to ICP-MS measurements. Confocal laser scanning microscopy (CLSM) displayed that MSN-Pt were uptaken fast by HepG-2 cells and concentrated within endosomes and lysosomes. In vitro MTT assay of MSN-Pt demonstrated an improved cytotoxicity against HepG-2 cells than that of free oxaliplatin. This is due to the fact that MSN-Pt expressed higher platinum intracellular uptake and more DNA binding (Pt-DNA adducts) than free oxaliplatin. Hence this work highlighted that the platinum loaded MSN nanoparticles could be a promising future intelligent drug delivery system.
authors.affiliation: State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, PR China; University of Chinese Academy of Sciences, Beijing 100039, PR China.
authors.forename: Hongyan
authors.initials: H
authors.lastname: He
authors.affiliation: Department of Chemical and Biomolecular Engineering, University of Notre Dame, Notre Dame, IN 46556, USA.
authors.forename: Haihua
authors.initials: H
authors.lastname: Xiao
authors.affiliation: State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, PR China; University of Chinese Academy of Sciences, Beijing 100039, PR China.
authors.forename: Huihui
authors.initials: H
authors.lastname: Kuang
authors.affiliation: State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, PR China.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Xie
authors.affiliation: State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, PR China.
authors.forename: Xuesi
authors.initials: X
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, PR China.
authors.forename: Xiabin
authors.initials: X
authors.lastname: Jing
authors.affiliation: State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, PR China. Electronic address: ybhuang@ciac.jl.cn.
authors.forename: Yubin
authors.initials: Y
authors.lastname: Huang
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D066241:Carbon-13 Magnetic Resonance Spectroscopy; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D016503:Drug Delivery Systems; D004705:Endocytosis / Q000187:drug effects; D056945:Hep G2 Cells; D006801:Humans; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D009944:Organoplatinum Compounds / Q000737:chemistry / Q000494:pharmacology*; D000077150:Oxaliplatin; D056951:Photoelectron Spectroscopy; D010984:Platinum / Q000378:metabolism; D016062:Porosity; D012822:Silicon Dioxide / Q000737:chemistry*; D017550:Spectroscopy, Fourier Transform Infrared; D013438:Sulfhydryl Compounds / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D013438:Sulfhydryl Compounds; D000077150:Oxaliplatin; D010984:Platinum; D012822:Silicon Dioxide
keywords: Conjugates; Drug delivery; Mesoporous silica nanoparticles (MSN); Oxaliplatin; Thiol-ene click