Synthesis of a Cationic Supramolecular Block Copolymer with Covalent and Noncovalent Polymer Blocks for Gene Delivery.
Synthesis of a Cationic Supramolecular Block Copolymer with Covalent and Noncovalent Polymer Blocks for Gene Delivery.
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DOI：
10.1021/acsami.6b15919
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发表时间：
2017-03
影响因子：
9.5
通讯作者：
Wumaier Yasen;Ruijiao Dong;Linzhu Zhou;Jieli Wu;C. Cao;A. Aini;Xinyuan Zhu
中科院分区：
文献类型：
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作者：
Wumaier Yasen;Ruijiao Dong;Linzhu Zhou;Jieli Wu;C. Cao;A. Aini;Xinyuan Zhu
设计和制备安全、高效的非病毒载体是实现临床基因治疗的关键科学问题。与共价阳离子聚合物相比，超分子阳离子聚合物具有独特的结构和特定的功能，例如低细胞毒性、优异的生物降解性和智能的环境响应性，在基因治疗方面显示出巨大的应用前景。然而，超分子基因载体在生理条件下容易降解，导致基因转染效率显著降低。为了实现基因的高效表达，需要为超分子基因载体提供适当的生物稳定性以克服各种细胞障碍。为此，通过β-环糊精/二茂铁的主客体识别作用，构建了一种由常规聚合物和非共价聚合物组成的新型阳离子超分子嵌段共聚物。所得的超分子嵌段共聚物从结构到功能完美地结合了常规聚合物和超分子聚合物的优点。这种超分子共聚物不仅具有有效浓缩pDNA以增强细胞摄取的能力，而且还具有在H2 O2触发下在癌细胞内释放pDNA的能力，其可以用作用于基因递送的有前景的非病毒递送载体。嵌段聚合物表现出低细胞毒性，良好的生物稳定性，优异的生物降解性，和智能响应性，归因于非共价键的动态/可逆性质。体外研究进一步表明，该超分子嵌段聚合物在癌细胞中表现出显著提高的基因转染效率。这项工作为未来开发用于特定癌症基因治疗的智能非病毒载体提供了一个替代平台。
The design and fabrication of safe and highly efficient nonviral vectors is the key scientific issue for the achievement of clinical gene therapy. Supramolecular cationic polymers have unique structures and specific functions compared to covalent cationic polymers, such as low cytotoxicity, excellent biodegradability, and smart environmental responsiveness, thereby showing great application prospect for gene therapy. However, supramolecular gene vectors are facile to be degraded under physiological conditions, leading to a significant reduction of gene transfection efficiency. In order to achieve highly efficient gene expression, it is necessary for supramolecular gene vectors being provided with appropriate biostability to overcome various cell obstacles. To this end, a novel cationic supramolecular block copolymer composed of a conventional polymer and a noncovalent polymer was constructed through robust β-cyclodextrin/ferrocene host-guest recognition. The resultant supramolecular block copolymer perfectly combines the advantages of both conventional polymers and supramolecular polymers ranging from structures to functions. This supramolecular copolymer not only has the ability to effectively condense pDNA for enhanced cell uptake, but also releases pDNA inside cancer cells triggered by H2O2, which can be utilized as a prospective nonviral delivery vehicle for gene delivery. The block polymer exhibited low cytotoxicity, good biostability, excellent biodegradability, and intelligent responsiveness, ascribing to the dynamic/reversible nature of noncovalent linkages. In vitro studies further illustrated that the supramolecular block polymer exhibited greatly improved gene transfection efficiency in cancer cells. This work offers an alternative platform for the exploitation of smart nonviral vehicles for specific cancer gene therapy in the future.