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Folic Acid/Peptides Modified PLGA–PEI–PEG Polymeric Vectors as Efficient Gene Delivery Vehicles: Synthesis, Characterization and Their Biological Performance

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Abstract

Polymeric vectors are safer alternatives for gene delivery owing to their advantages as compared to viral vectors. To improve the stability and transfection efficiency of poly(lactic-co-glycolic acid) (PLGA)- and poly(ethylenimine) (PEI)-based vectors, poly(ethylene glycol) (PEG), folic acid (FA), arginylglycylaspartic acid (RGD) peptides and isoleucine-lysine-valine-alanine-valine (IKVAV) peptides were employed and PLGA–PEI–PEG–FA and PLGA–PEI–PEG–RGD copolymers were synthesized. PLGA–PEI–PEG–FA/DNA, PLGA–PEI–PEG–RGD/DNA and PLGA–PEI–PEG–RGD/IKVAV/DNA nanocomplexes (NCs) were formed through bulk mixing. The structure and properties, including morphology, particle size, surface charge and DNA encapsulation, of NCs were studied. Robust NCs with spherical shape, uniform size distribution and slightly positive charge were able to completely bind DNA above their respective N/P ratios. The critical N/P ratio for PLGA–PEI–PEG–FA/DNA, PLGA–PEI–PEG–RGD/DNA and PLGA–PEI–PEG–RGD/IKVAV/DNA NCs was identified to be 12:1, 8:1 and 10:1, respectively. The covalent modification of PEI through a combination of biodegradable PLGA, hydrophilic PEG and targeting motifs significantly decreased the cytotoxicity of PEI. The developed NCs showed both N/P ratio and cell type-dependent transfection efficiency. An increase in N/P ratio resulted in increased transfection efficiency, and much improved transfection efficiency of NCs was observed above their respective critical N/P ratios. This study provides a promising means to produce polymeric vectors for gene delivery.

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Acknowledgements

This work was supported by the Hong Kong Research Grants Council through a GRF grant (Grant No: HKU 718109E); the Guangdong Special Support Plan for High Level Talents of China (Grant No: 2015TQ01R546) and the Hubei Natural Science Foundation of China (Grant No: 2018CFC874).

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  1. Chaoyu Liu and Yuancai Xie have contributed equally.

Authors and Affiliations

  1. Department of Research and Development, Shiningbiotek Co., Ltd, Shenzhen, 518055, People’s Republic of China

    Chaoyu Liu, Xiaohua Li & Xumei Yao

  2. Department of Thoracic, Peking University Shenzhen Hospital, Shenzhen, 518036, People’s Republic of China

    Yuancai Xie

  3. Laboratory of Chinese Herbal Pharmacology, Oncology Center, Renmin Hospital, Hubei University of Medicine, Shiyan, 442000, People’s Republic of China

    Xuanbin Wang & Fengjun Cao

  4. Hubei Key Laboratory of Wudang Local Chinese Medicine Research, Shiyan, 442000, People’s Republic of China

    Xuanbin Wang

  5. Department of Mechanical Engineering, The University of Hong Kong, Pokfulam, Hong Kong, People’s Republic of China

    Min Wang

  6. Department of Oncology, Weihai Central Hospital, Weihai, People’s Republic of China

    Zongxian Li

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  1. Chaoyu Liu
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Liu, C., Xie, Y., Li, X. et al. Folic Acid/Peptides Modified PLGA–PEI–PEG Polymeric Vectors as Efficient Gene Delivery Vehicles: Synthesis, Characterization and Their Biological Performance. Mol Biotechnol 63, 63–79 (2021). https://doi.org/10.1007/s12033-020-00285-5

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