title: Linear polyethylenimine-plasmid DNA nanoparticles are ototoxic to the cultured sensory epithelium of neonatal mice.
abstract: Polyethylenimine (PEI) has been demonstrated to be an effective non‑viral synthetic polymer for efficient gene delivery amongst various cell types in vitro and in vivo. In the present study, 25 kDa linear PEI (L‑PEI) was used to transfer plasmid DNA (pDNA), encoding the enhanced green fluorescent protein reporter gene, into the cultured cochlear epithelium of neonatal mice. The 25 kDa L‑PEI/pDNA nanoparticles were generated in phosphate‑buffered saline prior to transfection. Sensory epithelial cells were transfected using an appropriate weight ratio of L‑PEI and pDNA. However, the use of higher L‑PEI/pDNA ratios, which result in the generation of a greater number of nanoparticles, induced significant damage to the sensory epithelial cells, as demonstrated by immunofluorescent and transmission electron microscopy analyses. These results indicated that precautionary measures are required with regard to the use of PEI nanoparticles in nanomedicine, and emphasized the requirement for thorough physicochemical characterization and toxicity testing for each polymer vector prior to the construction of nanotechnology systems for use in clinical applications. The development of effective management techniques for potential nano‑ototoxicity risks is of considerable significance to the clinical applications of nanoparticles.
authors: Department of Otorhinolaryngology, Nanjing Drum Tower Hospital, Nanjing, Jiangsu 210008, P.R. China.
authors: Han
authors: H
authors: Zhou
authors: Department of Otorhinolaryngology, Nanjing Drum Tower Hospital, Nanjing, Jiangsu 210008, P.R. China.
authors: Xiaofeng
authors: X
authors: Ma
authors: Department of Clinical Medicine, Medical School of Nanjing University, Nanjing, Jiangsu 210093, P.R. China.
authors: Yongze
authors: Y
authors: Liu
authors: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu 210093, P.R. China.
authors: Lei
authors: L
authors: Dong
authors: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu 210093, P.R. China.
authors: Yi
authors: Y
authors: Luo
authors: Department of Otorhinolaryngology, Nanjing Drum Tower Hospital, Nanjing, Jiangsu 210008, P.R. China.
authors: Guangjie
authors: G
authors: Zhu
authors: Department of Otorhinolaryngology, Nanjing Drum Tower Hospital, Nanjing, Jiangsu 210008, P.R. China.
authors: Xiaoyun
authors: X
authors: Qian
authors: Department of Otorhinolaryngology, Nanjing Drum Tower Hospital, Nanjing, Jiangsu 210008, P.R. China.
authors: Jie
authors: J
authors: Chen
authors: Department of Otorhinolaryngology, Nanjing Drum Tower Hospital, Nanjing, Jiangsu 210008, P.R. China.
authors: Lin
authors: L
authors: Lu
authors: Department of Otorhinolaryngology, Nanjing Drum Tower Hospital, Nanjing, Jiangsu 210008, P.R. China.
authors: Junguo
authors: J
authors: Wang
authors: Department of Otorhinolaryngology, Nanjing Drum Tower Hospital, Nanjing, Jiangsu 210008, P.R. China.
authors: Xia
authors: X
authors: Gao
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D003051:Cochlea / Q000378:metabolism; D004848:Epithelium / Q000378:metabolism* / Q000648:ultrastructure; D005260:Female; D015870:Gene Expression; D018014:Gene Transfer Techniques; D006198:Hair Cells, Auditory / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D008297:Male; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry* / Q000633:toxicity* / Q000648:ultrastructure; D010957:Plasmids / Q000737:chemistry* / Q000235:genetics*; D011094:Polyethyleneimine / Q000737:chemistry*; D014162:Transfection
chemical_list: D011094:Polyethyleneimine