title: Hypoxia-sensitive bis(2-(2'-benzothienyl)pyridinato-N,C(3'))iridium[poly(n-butyl cyanoacrylate]/chitosan nanoparticles and their phosphorescence tumor imaging in vitro and in vivo.
abstract: A new hypoxia-sensitive coordination compound, bis(2-(2'-benzothienyl)pyridinato-N,C(3'))iridium[poly(n-butyl cyanoacrylate)], hereafter denoted as (btp)2Ir(PBCA), is synthesized and characterized by (13)C nuclear magnetic resonance (NMR) and Fourier transform infrared spectroscopy (FTIR). (btp)2Ir(PBCA)/chitosan [(btp)2Ir(PBCA)/CS] nanoparticles (NPs) with a core-shell structure are prepared by a two-step fabrication process. The size distributions of these NPs are measured with a Malvern size analyzer, and their morphology is observed by transmission electron microscopy (TEM). The functional groups on the surface are confirmed by FTIR. Phosphorescence spectra are obtained and lifetimes are determined with a spectrophotofluorometer and a time-correlated single photon counting (TCSPC) apparatus, respectively. HeLa and CT26 cell lines are used to examine the cytotoxicity by the MTT assay, as well as to determine the imaging capability of the samples in air and nitrogen atmospheres, respectively. Tumor-bearing mouse models of colon adenocarcinoma are used for tumor imaging in vivo, and the imaging effect is evaluated with a Maestro 2 fluorescence imaging system. Compared with the hypoxia-associated probe bis(2-(2'-benzothienyl)pyridinato-N,C(3'))iridium(acetylacetonate) (BTP), the phosphorescence lifetime of (btp)2Ir(PBCA)/CS NPs significantly decreases, but the hypoxia-sensitivity increases after preparation of NPs. Apart from the significantly lower cytotoxicity, (btp)2Ir(PBCA)/CS NPs also enhance the tumor imaging effect by more than 10 times, maintaining the phosphorescence signal in tumor tissue for over 24 h and significantly decreasing the phosphorescence signal in normal tissue in vivo compared with the BTP probe.
authors.affiliation: Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, P. R. China. wudaocheng@mail.xjtu.edu.cn.
authors.forename: Yun
authors.initials: Y
authors.lastname: Zeng
authors.forename: Shaojuan
authors.initials: S
authors.lastname: Zhang
authors.forename: Menghui
authors.initials: M
authors.lastname: Jia
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.forename: Jin
authors.initials: J
authors.lastname: Shang
authors.forename: Youmin
authors.initials: Y
authors.lastname: Guo
authors.forename: Jianhua
authors.initials: J
authors.lastname: Xu
authors.forename: Daocheng
authors.initials: D
authors.lastname: Wu
mesh_terms: D000818:Animals; D015687:Cell Hypoxia / Q000502:physiology; D002478:Cells, Cultured; D048271:Chitosan / Q000737:chemistry; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000737:chemistry; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry; D004659:Enbucrilate / Q000737:chemistry; D006367:HeLa Cells; D006801:Humans; D007495:Iridium / Q000737:chemistry; D049408:Luminescent Agents / Q000138:chemical synthesis / Q000737:chemistry; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D057054:Molecular Imaging / Q000379:methods; D053758:Nanoparticles / Q000737:chemistry*; D009369:Neoplasms / Q000175:diagnosis* / Q000378:metabolism; D010100:Oxygen / Q000494:pharmacology*
chemical_list: D056831:Coordination Complexes; D004337:Drug Carriers; D049408:Luminescent Agents; C000591156:bis(2-(2'-benzothienyl)pyridinato-N,C3')iridium(poly(n-butyl cyanoacrylate)); D007495:Iridium; D048271:Chitosan; D004659:Enbucrilate; D010100:Oxygen