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Review
. 2020 Mar 30:15:2131-2150.
doi: 10.2147/IJN.S222419. eCollection 2020.

Biodegradable Polymers for Gene-Delivery Applications

Chih-Kuang Chen  1 , Ping-Kuan Huang  2 , Wing-Cheung Law  3 , Chia-Hui Chu  4 , Nai-Tzu Chen  5 , Leu-Wei Lo  4
Affiliations
Review

Biodegradable Polymers for Gene-Delivery Applications

Chih-Kuang Chen et al. Int J Nanomedicine. .

Abstract

Gene-based therapies have emerged as a new modality for combating a myriad of currently incurable diseases. However, the fragile nature of gene therapeutics has significantly hampered their biomedical applications. Correspondingly, the development of gene-delivery vectors is of critical importance for gene-based therapies. To date, a variety of gene-delivery vectors have been created and utilized for gene delivery. In general, they can be categorized into viral- and non-viral vectors. Due to safety issues associated with viral vectors, non-viral vectors have recently attracted much more research focus. Of these non-viral vectors, polymeric vectors, which have been preferred due to their low immunogenicity, ease of production, controlled chemical composition and high chemical versatility, have constituted an ideal alternative to viral vectors. In particular, biodegradable polymers, which possess advantageous biocompatibility and biosafety, have been considered to have great potential in clinical applications. In this context, the aim of this review is to introduce the recent development and progress of biodegradable polymers for gene delivery applications, especially for their chemical structure design, gene delivery capacity and additional biological functions. Accordingly, we first define and categorize biodegradable polymers, followed by describing their corresponding degradation mechanisms. Various types of biodegradable polymers resulting from natural and synthetic polymers will be introduced and their applications in gene delivery will be examined. Finally, a future perspective regarding the development of biodegradable polymer vectors will be given.

Keywords: biodegradable polymers; gene delivery; gene therapy; non-viral vectors; polymeric vectors.

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Conflict of interest statement

The authors report no conflicts of interest in this work.

Figures

Figure 1
Figure 1
Gene delivery mechanism of polyplexes.
Figure 2
Figure 2
Chemical structures of conventional CPs for gene delivery.
Figure 3
Figure 3
Chemical structures of natural biodegradable polymers for gene delivery.
Figure 4
Figure 4
Chemical structures of synthetic biodegradable polymers for gene delivery.
Figure 5
Figure 5
Synthetic strategy of poly-siRNA.
Figure 6
Figure 6
Preparation of TCS-g-poly(PEGMA-co-DMAEMA)-FA/pDNA polyplexes.
Figure 7
Figure 7
Preparation of C-siRNA-HPD complexes.
Figure 8
Figure 8
Synthesis of CPLA nanocapsules, and the co-loading of hydrophilic siRNA and hydrophobic anticancer drugs. Chen C-K, Law WC, Aalinkeel R, et al. Biodegradable cationic polymeric nanocapsules for overcoming multidrug resistance and enabling drug-gene co-delivery to cancer cells. Nanoscale. 2014;6 (3):1567–1572. Reproduced by permission of The Royal Society of Chemistry.
Figure 9
Figure 9
Synthetic route of P(MAC-co-DTC)-g-PEI copolymers. Reprinted with permission from He F, Wang CF, Jiang T, Han B, Zhuo RX. Poly[(5-methyl-5-allylox-ycarbonyl-trimethylene carbonate)-co-(5,5-dimethyl-trimethylene car-bonate)] with grafted polyethylenimine as biodegradable polycations for efficient gene delivery. Biomacromolecules. 2010;11(11): 3028–3035. Copyright (2010) American Chemical Society.
Figure 10
Figure 10
Synthesis of RGD-PEG-SS-PEI. Reprinted with permission from Lei Y, Wang J, Xie C, et al. Glutathione-sensitive RGD-poly(ethy-lene glycol)-SS-polyethylenimine for intracranial glioblastoma tar- geted gene delivery. J Gene Med. 2013;15(8–9):291–305. Copyright © 2013 John Wiley and Sons.
See this image and copyright information in PMC

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