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Degradable Polyethylenimine-Based Gene Carriers for Cancer Therapy

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Abstract

Gene therapy using recombinant DNA or gene silencing using siRNA have become a prominent area of research in cancer therapy. However, their use in clinical applications is limited due to overall safety concerns and suboptimal efficacy. Although non-viral vectors such as polycationic polymers do not offer the same level of transfection efficiency as their viral counterparts, they still demonstrate immense potential as alternatives to viral vectors, given their versatility, low immunogenicity, ease of large-scale production, and ability to accelerate gene transfer with well-designed delivery platforms. Among these polymers, polyethylenimine (PEI) is considered a state-of-the-art gene carrier, owing to its ability to improve gene transfer capacity and intracellular delivery. Nonetheless, PEI suffers from the critical shortcoming of non-degradability that can lead to severe cytotoxic effects, despite the fact that the level of this toxicity decreases with molecular weight (MW). As a result, a considerable amount of effort has been devoted to designing low-MW PEI derivatives with degradable linkages. This review will categorize the recent advances in these degradable PEI derivatives based on their degradable chemistries, including ester, disulfide, imine, carbamate, amide, and ketal linkages, and summarize their application in gene therapies against various major cancer malignancies.

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Fig. 1

Adapted from [19] with permission from the American Chemical Society

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Adapted from [52] with kind permission from Elsevier

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Adapted from [60] with kind permission from Springer

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Adapted from [69] with kind permission from Wiley

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Adapted from [80] with kind permission from the National Academy of Sciences

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Adapted from [24] with kind permission from Elsevier

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Adapted from [130] with kind permission from the American Chemical Society

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Adapted from [134] with kind permission from Elsevier

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Adapted from [136] with kind permission from the Royal Society of Chemistry

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Adapted from [143] with kind permission from Taylor & Francis Group

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Adapted from [149] with kind permission from Dove Medical Press

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Acknowledgements

We thank the National Natural Science Foundation of China (Grant No. 81573369) and the Natural Science Foundation of Jiangsu Province (Grant No. BK20140659). This work was also supported by the National Research Foundation of Korea (Grant No. NRF-2014R1A1A2007163) funded by the Ministry of Science, ICT and Future Planning (MSIF) and the Outstanding Youth Fund of Jiangsu Province of China (Grant No. BK20160031).

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    Authors and Affiliations

    1. State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, Nanjing, 210009, China

      Hu-Lin Jiang, Lei Xing, Yu-Jing He & Yong Zhu

    2. Center for Nanomedicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, 02115, USA

      Mohammad Ariful Islam

    3. Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, 02115, USA

      Jannatul Firdous

    4. Nanotechnology Engineering Program, University of Waterloo, Waterloo, Canada

      Wuji Cao

    5. Department of Plastic Surgery, Institute of Dermatology and Plastic Surgery, Cleveland Clinic, 9500 Euclid Ave, Cleveland, OH, 44195, USA

      Ki-Hyun Cho

    6. Department of Agricultural Biotechnology and Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul, 08826, Republic of Korea

      Hui-Shan Li & Chong-Su Cho

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    1. Hu-Lin Jiang
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    Correspondence to Chong-Su Cho.

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    This article is part of the Topical Collection “Polymeric Gene Delivery Systems”; edited by Yiyun Cheng.

    H.-L. Jiang and M.A. Islam contributed equally in this work.

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    Jiang, HL., Islam, M.A., Xing, L. et al. Degradable Polyethylenimine-Based Gene Carriers for Cancer Therapy. Top Curr Chem (Z) 375, 34 (2017). https://doi.org/10.1007/s41061-017-0124-9

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    • DOI: https://doi.org/10.1007/s41061-017-0124-9

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