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WIREs Nanomed Nanobiotechnol
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Degradable branched polycationic systems for nucleic acid delivery

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Abstract Nowadays, nucleic acid‐based therapy has become a promising way for the treatment of various malignant diseases like cancers. However, the process of nucleic acid delivery is hampered by several extracellular and intracellular obstacles. To overcome these obstacles, many nucleic acid delivery carriers have been developed to achieve improved safety and enhanced gene transfection performance. Among these carriers, degradable branched polycations have attracted much attention due to their good responsive degradability and impressive transfection performances. In this review, we mainly summarized the redox‐ and pH‐responsive degradable branched polycationic systems used for nucleic acid delivery. For responsive degradable branched polycationic systems, the preparation methods were introduced, where amino‐epoxy ring‐opening reaction as a novel step growth approach was mainly presented. The properties of redox‐ and pH‐responsive degradable branched polycationic systems were subsequently introduced and highlighted. We hope this brief review will motivate the delicate design of responsive degradable branched polycationic systems for potential clinical applications. This article is categorized under: Biology‐Inspired Nanomaterials > Nucleic Acid‐Based Structures
(a) Schematic illustration of the construction of SS‐HPT/Lv‐CD hybrid nanovector and the resultant therapeutic processes of gene therapy with 5‐FC against glioma. (b) Representative T2WI images of intracranial tumors monitored by MRI on Day 5–24 after C6 cell implantation with different treatments. (Reprinted with permission from Fan et al. (). Copyright 2019 Wiley‐VCH)
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(a) Schematic illustration of multifunctional aminoglycosides‐based rbranched polycationic systems with redox‐responsive degradability for nuleic acid delivery. (b) Electrophoretic mobility of pDNA in the complexes of polyaminoglycosides. (c) Morphologies of typical HPN/pDNA and SS‐HPN/pDNA complexes treated with or without NaBH4. (Reprinted with permission from Huang et al. (). Copyright 2016 Elesvier)
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(a) The preparation process of branched polycation (TE) though amino‐epoxy ring‐opening polymerization of 1,3,5‐triglycidyl isocyanurate (TGIC) and ethylenediamine (ED), (b) in vitro transfection performances of corresponding TEs, and (c) in vivo therapeutic efficiency of p53 plasmid deliveried by TE3 treating tumors. (Reprinted with permission from Duan et al. (). Copyright 2016 ACS)
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The preparation process of branched polycations through amino‐epoxy ring‐opening polymerization. (Reprinted with permission from Zhang et al. (). Copyright 2014 ACS)
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Schematic illustration of nucleic acid delivery mediated by degradable branched polycationic systems
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(a) Schematic illustration of the preparation of fluorinated acid‐responsive polycation (ARP‐F) and its resultant pCas9‐survivin delivery process. (b) in vitro gene transfection efficiencies of ARP/pDNA, ARP‐F/pDNA, and PEI/pDNA complexes in A549 cell lines. (c) Cleavage detection of survivin loci in A549 cell lines treated with PBS (control) and ARP2‐F90/pCas9‐surv complexes in the absence (−) and presence (+) of T7EI. (d) Relative volumes of A549 tumors after different treatments. (Reprinted with permission from Qi et al. (). Copyright 2018 Wiley‐VCH)
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Biology-Inspired Nanomaterials > Nucleic Acid-Based Structures

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