title: Reduction of polyethylenimine-coated iron oxide nanoparticles induced autophagy and cytotoxicity by lactosylation.
abstract: Superparamagnetic iron oxide (SPIO) nanoparticles are excellent magnetic resonance contrast agents and surface engineering can expand their applications. When covered with amphiphilic alkyl-polyethyleneimine (PEI), the modified SPIO nanoparticles can be used as MRI visible gene/drug delivery carriers and cell tracking probes. However, the positively charged amines of PEI can also cause cytotoxicity and restricts their further applications. In this study, we used lactose to modify amphiphilic low molecular weight polyethylenimine (C12-PEI2K) at different lactosylation degree. It was found that the N-alkyl-PEI-lactobionic acid wrapped SPIO nanocomposites show better cell viability without compromising their labelling efficacy as well as MR imaging capability in RAW 264.7 cells, comparing to the unsubstituted ones. Besides, we found the PEI induced cell autophagy can be reduced via lactose modification, indicating the increased cell viability might rely on down-regulating autophagy. Thus, our findings provide a new approach to overcome the toxicity of PEI wrapped SPIO nanocomposites by lactose modification.
authors.affiliation: National Engineering Research Center for Biomaterials.
authors.forename: Jiuju
authors.initials: J
authors.lastname: Du
authors.affiliation: National Engineering Research Center for Biomaterials; Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 200031, P. R. China and.
authors.forename: Wencheng
authors.initials: W
authors.lastname: Zhu
authors.affiliation: National Engineering Research Center for Biomaterials.
authors.forename: Li
authors.initials: L
authors.lastname: Yang
authors.affiliation: National Engineering Research Center for Biomaterials; School of Medical Imaging, North Sichuan Medical College, Nanchong, 637000, P.R. China.
authors.forename: Changqiang
authors.initials: C
authors.lastname: Wu
authors.affiliation: National Engineering Research Center for Biomaterials.
authors.forename: Bingbing
authors.initials: B
authors.lastname: Lin
authors.affiliation: National Engineering Research Center for Biomaterials.
authors.forename: Jun
authors.initials: J
authors.lastname: Wu
authors.affiliation: National Engineering Research Center for Biomaterials.
authors.forename: Rongrong
authors.initials: R
authors.lastname: Jin
authors.affiliation: National Engineering Research Center for Biomaterials.
authors.forename: Taipeng
authors.initials: T
authors.lastname: Shen
authors.affiliation: National Engineering Research Center for Biomaterials; Department of Radiology, West China Hospital, Sichuan University, Chengdu, 610065, P.R. China.
authors.forename: Hua
authors.initials: H
authors.lastname: Ai
keywords: MRI; RAW 264.7; SPIO; autophagy; lactosylation; polyethyleneimine