title: Polyethylene glycol modification decreases the cardiac toxicity of carbonaceous dots in mouse and zebrafish models.
abstract: OBJECTIVE
  Carbonaceous dots (CDs), which have been used for diagnosis, drug delivery and gene delivery, are accumulated in heart at high concentrations. To improve their biocompatibility, polyethylene glycol-modified CDs (PEG-CDs) were prepared. In this study we compared the cardiac toxicity of CDs and PEG-CDs in mouse and zebrafish models.
  
  
  METHODS
  Mice were intravenously treated with CDs (size: 4.9 nm, 5 mg·kg(-1)·d(-1)) or PEG-CDs (size: 8.3 nm, 5 mg·kg(-1)·d(-1)) for 21 d. Their blood biochemistry indices, ECG, and histological examination were examined for evaluation of cardiac toxicity. CDs or PEG-CDs was added in incubator of cmlc2 transgenic Zebrafish embryos at 6 hpf, and the shape and size of embryos' hearts were observed at 48 hpf using a fluorescent microscope. Furthermore, whole-mount in situ hybridization was used to examine the expression of early cardiac marker gene (clml2) at 48 hpf.
  
  
  RESULTS
  Administration of CDs or PEG-CDs in mice caused mild, but statistically insignificant reduction in serum creatine kinase (CK) and lactate dehydrogenase (LDH) levels detected at 7 d, which were returned to the respective control levels at 21 d. Neither CDs nor PEG-CDs caused significant changes in the morphology of heart cells. Administration of CDs, but not PEG-CDs, in mice caused marked increase of heart rate. Both CDs and PEG-CDs did not affect other ECG parameters. In the zebrafish embryos, addition of CDs (20 μg/mL) caused heart development delay, whereas addition of CDs (80 μg/mL) led to heart malformation. In contrast, PEG-CDs caused considerably small changes in heart development, which was consistent with the results from the in situ hybridization experiments.
  
  
  CONCLUSIONS
  CDs causes greater cardiac toxicity, especially regarding heart development. Polyethylene glycol modification can attenuate the cardiac toxicity of CDs.
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.
authors.forename: Jian-tao
authors.initials: JT
authors.lastname: Chen
authors.affiliation: Joint Laboratory of Reproductive Medicine, Sichuan University-The Chinese University of Hong Kong, West China Second University Hospital, Sichuan University, Chengdu 610041, China.
authors.forename: Hua-qin
authors.initials: HQ
authors.lastname: Sun
authors.affiliation: Key Laboratory of Smart Drug Delivery (Fudan University), Ministry of Education, School of Pharmacy, Fudan University, Shanghai 201203, China.
authors.forename: Wei-liang
authors.initials: WL
authors.lastname: Wang
authors.affiliation: Joint Laboratory of Reproductive Medicine, Sichuan University-The Chinese University of Hong Kong, West China Second University Hospital, Sichuan University, Chengdu 610041, China.
authors.forename: Wen-ming
authors.initials: WM
authors.lastname: Xu
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: He
authors.affiliation: Key Laboratory of Smart Drug Delivery (Fudan University), Ministry of Education, School of Pharmacy, Fudan University, Shanghai 201203, China.
authors.forename: Shun
authors.initials: S
authors.lastname: Shen
authors.affiliation: Key Laboratory of Smart Drug Delivery (Fudan University), Ministry of Education, School of Pharmacy, Fudan University, Shanghai 201203, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Qian
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.
authors.forename: Hui-le
authors.initials: HL
authors.lastname: Gao
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D002244:Carbon / Q000008:administration & dosage / Q000737:chemistry* / Q000633:toxicity*; D066126:Cardiotoxicity / Q000517:prevention & control*; D004195:Disease Models, Animal; D006321:Heart / Q000187:drug effects* / Q000196:embryology / Q000502:physiology; D006330:Heart Defects, Congenital / Q000139:chemically induced; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D051379:Mice; D049329:Nanostructures / Q000008:administration & dosage / Q000737:chemistry* / Q000633:toxicity* / Q000648:ultrastructure; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology*; D015027:Zebrafish
chemical_list: D011092:Polyethylene Glycols; D002244:Carbon