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Multifunctional peptide conjugated amphiphilic cationic copolymer for enhancing ECs targeting, penetrating and nuclear accumulation

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An Erratum to this article was published on 02 September 2020

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Abstract

Gene therapy has drawn great attention in the treatments of many diseases, especially for cardiovascular diseases. However, the development of gene carriers with low cytotoxicity and multitargeting function is still a challenge. Herein, the multitargeting REDV-G-TAT-GNLS peptide was conjugated to amphiphilic cationic copolymer poly(ε-caprolactone-co-3(S)-methyl-morpholine-2,5-dione)-g-polyethyleneimine (PCLMD-g-PEI) via a heterobifunctional orthopyridyl disulfide-poly(ethylene glycol)-N-hydroxysuccinimide (OPSS-PEG-NHS) linker to prepare PCLMD-g-PEI-PEG-REDV-G-TAT-G-NLS copolymers with the aim to develop the gene carriers with low cytotoxicity and high transfection efficiency. The multitargeting micelles were prepared from PCLMD-g-PEI-PEG-REDV-G-TAT-G-NLS copolymers by selfassembly method and used to load pEGFP-ZNF580 plasmids (pDNA) to form gene complexes for enhancing the proliferation and migration of endothelial cells (ECs). The loading pDNA capacity was proved by agarose gel electrophoresis assay. These multitargeting gene complexes exhibited low cytotoxicity by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The high internalization efficiency of these gene complexes was confirmed by flow cytometry. The results of in vitro transfection demonstrated that these multitargeting gene complexes possessed relatively high transfection efficiency. The rapid migration of ECs transfected by these gene complexes was verified by wound healing assay. Owing to ECs-targeting ability, cell-penetrating ability and nuclear targeting capacity of REDV-G-TAT-G-NLS peptide, the multitargeting polycationic gene carrier with low cytotoxicity and high transfection efficiency has great potential in gene therapy.

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Change history

  • 02 September 2020

    The authors regret that there was an error in our publication. Considering Lingchuang Bai made great contributions to this work, Xinghong Duo and Lingchuang Bai should be co-first authors, but there was no statement that ���Xinghong Duo and Lingchuang Bai contributed equally to this work���. The authors would like to apologize for any inconvenience caused.

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Acknowledgments

This project was supported by the National Natural Science Foundation of China (Grant Nos. 51673145, 51873149, 21875157 and 51963018), the National Key Research and Development Program of China (Grant No. 2016YFC1100300), the International Science and Technology Cooperation Program of China (Grant No. 2013DFG52040).

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Authors and Affiliations

  1. School of Chemical Engineering and Technology, Tianjin University, Tianjin, 300350, China

    Xinghong Duo, Lingchuang Bai, Jun Wang, Jintang Guo, Xiangkui Ren & Yakai Feng

  2. School of Chemistry and Chemical Engineering, Qinghai University for Nationalities, Xining, 810007, China

    Xinghong Duo

  3. Collaborative Innovation Center of Chemical Science and Chemical Engineering (Tianjin), Tianjin, 300350, China

    Xiangkui Ren & Yakai Feng

  4. Key Laboratory of Systems Bioengineering (Ministry of Education), Tianjin University, Tianjin, 300072, China

    Xiangkui Ren & Yakai Feng

  5. Department of Hepatopancreatobiliary and Splenic Medicine, Affiliated Hospital, Logistics University of People’s Armed Police Force, Tianjin, 300162, China

    Shihai Xia

  6. Department of Physiology and Pathophysiology, Logistics University of People’s Armed Police Force, Tianjin, 300162, China

    Wencheng Zhang

  7. Institute of Drug Research (IDR), School of Pharmacy-Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, 91905, Israel

    Abraham Domb

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  1. Xinghong Duo
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  2. Lingchuang Bai
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  3. Jun Wang
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  4. Jintang Guo
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  5. Xiangkui Ren
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  8. Abraham Domb
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  9. Yakai Feng
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Correspondence to Yakai Feng.

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Duo, X., Bai, L., Wang, J. et al. Multifunctional peptide conjugated amphiphilic cationic copolymer for enhancing ECs targeting, penetrating and nuclear accumulation. Front. Chem. Sci. Eng. 14, 889–901 (2020). https://doi.org/10.1007/s11705-020-1919-8

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  • DOI: https://doi.org/10.1007/s11705-020-1919-8

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