Xu Zhangyan, Lai Junping, Tang Rupei, Ji Weihang, Wang Rui, Wang Jun, Wang Chun
School of Pharmaceutical Science, Jiangnan University, 1800 Lihu Road, Wuxi, Jiangsu Province, 214122, P. R. China.
Macromol Biosci. 2014 Jul;14(7):1015-24. doi: 10.1002/mabi.201400004. Epub 2014 Apr 4.
A new type of homopolymers, PMAOE, bearing acid-cleavable cationic side-chains is synthesized and characterized. PMAOE is obtained via free radical polymerization, and they could efficiently bind and condense plasmid DNA at neutral pH. The strength of DNA binding is dependent on the length of PMAOE chains. NMR analysis reveals that hydrolysis of the ortho ester group of PMAOE follows an exocyclic mechanism and the rate of hydrolysis is much accelerated at mildly acidic pH, leading to accelerated disruption of polyplexes and release of DNA in mildly acidic environment. PMAOE is not toxic to cultured NIH 3T3 and COS-7 cells measured by MTT. This study demonstrates a unique mechanism of achieving pH-modulated binding and release of DNA from polymers with potential applications for gene delivery.
合成并表征了一种新型带有可酸裂解阳离子侧链的均聚物PMAOE。PMAOE通过自由基聚合获得，在中性pH条件下它们能够有效地结合并凝聚质粒DNA。DNA结合强度取决于PMAOE链的长度。核磁共振分析表明，PMAOE的原酸酯基团水解遵循外环机制，在弱酸性pH条件下水解速率大大加快，导致在弱酸性环境中多聚体加速破坏和DNA释放。通过MTT法测定，PMAOE对培养的NIH 3T3和COS-7细胞无毒。本研究展示了一种实现pH调节的DNA从聚合物上结合与释放的独特机制，在基因递送方面具有潜在应用。
