School of Chemistry and Chemical Engineering, State Key Laboratory of Metal Matrix Composites, Shanghai Jiao Tong University , 800 Dongchuan Road, Shanghai 200240, China.
School of Life Science and Biotechnology, Shanghai Jiao Tong University , 800 Dongchuan Road, Shanghai 200240, P. R. China.
ACS Appl Mater Interfaces. 2017 Mar 15;9(10):9006-9014. doi: 10.1021/acsami.6b15919. Epub 2017 Mar 2.
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 HO, 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.
安全高效的非病毒载体的设计与制备是非病毒基因治疗临床应用的关键科学问题。超分子阳离子聚合物与共价阳离子聚合物相比，具有独特的结构和特定的功能，如低细胞毒性、良好的生物可降解性和智能环境响应性，因此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。为了实现高效的基因表达，超分子基因载体需要具有适当的生物稳定性来克服各种细胞障碍。为此，通过强β-环糊精/二茂铁主客体识别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。所得超分子嵌段共聚物完美地结合了常规聚合物和超分子聚合物的结构和功能优势。这种超分子共聚物不仅具有有效压缩 pDNA 以增强细胞摄取的能力，而且能够在 HO 触发下在癌细胞内释放 pDNA，可作为一种有前途的非病毒递送载体用于基因递送。该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，这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大大提高的基因转染效率。这项工作为未来特定癌症基因治疗的智能非病毒载体的开发提供了一个替代平台。
