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Integration of Polylactide into Polyethylenimine Facilitates the Safe and Effective Intracellular siRNA Delivery

Sciprofile linkGuo-Bin Ding, Sciprofile linkXue Meng, Sciprofile linkPeng Yang, Sciprofile linkBinchun Li, Sciprofile linkRoland H. Stauber, Sciprofile linkZhuoyu Li
Published: 14 February 2020
 by  MDPI
Polymers , Volume 12; doi:10.3390/polym12020445

Abstract: Polyethylenimine (PEI) is a gold standard polymer with excellent transfection efficacy, yet its severe toxicity and nondegradability hinders its therapeutic application as a gene delivery vector. To tackle this problem, herein we incorporated the biodegradable polylactide (PLA) into the branched PEI by synthesizing a PEI-PLA copolymer via a facile synthetic route. PLA modification significantly improved the cytocompatibility of PEI, PEI-PLA copolymer showed much higher cell viability than PEI as verified in three different human cancer cell lines (HCT116, HepG2 and SKOV3). Interestingly, the PEI-PLA copolymer could effectively bind siRNA targeting PKM2, and the obtained polyplex displayed much higher stability in serum than naked siRNA as determined by agarose gel electrophoresis. Moreover, cellular uptake study demonstrated that PEI-PLA could efficiently deliver the Cy5-labled siRNA into the three tested cancer cell lines, and the transfection efficiency is equivalent to the commercial Lipofectamine® 2000. Finally, it is noteworthy that the polyplex is comparable to Lipo2000 in down-regulating the expression of PKM2 at both mRNA and protein level as measured by q-PCR and western blotting, respectively. Overall, the PEI-PLA copolymer developed in this study has the potential to be developed as a versatile carrier for safe and effective delivery of other nucleic acid-based agents.
Keywords: cytotoxicity / transfection efficiency / Serum Stability / PEI-PLA copolymer / siRNA targeting PKM2

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