Cao Xiaodan, Chen Chao, Yu Haijun, Wang Ping
Biomedical Nanotechnology Center, State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, 200237, People's Republic of China,
Biotechnol Lett. 2015 Jan;37(1):81-8. doi: 10.1007/s10529-014-1664-5. Epub 2014 Sep 26.
Among various enzyme-based therapies, enzyme-prodrug therapy (EPT) promises minimized side effects in that it activates non-toxic prodrugs locally where the enzymes are placed. The success of such an approach requires high enzyme stability against both structural denaturation and potential immunogenicity. This work examines the efficiency of nanoparticles for enzyme protection in EPT applications. Specifically, horseradish peroxidase (HRP)-encapsulated chitosan nanoparticles (HRP-CSNP) were constructed and examined with respect to stability enhancement. HRP-CSNP retained enzyme activity and had improved stability at 37 °C in the presence of a denaturant, urea. The nanoparticles effectively bound to the surface of human breast cancer cell Bcap37 and led to over 80 % cell death when applied with a prodrug indole-3-acetic acid.
在各种基于酶的疗法中，酶前药疗法（EPT）有望将副作用降至最低，因为它能在酶所在的局部区域激活无毒前药。这种方法的成功需要酶对结构变性和潜在免疫原性具有高稳定性。这项工作研究了纳米颗粒在EPT应用中对酶的保护效率。具体而言，构建了包裹辣根过氧化物酶（HRP）的壳聚糖纳米颗粒（HRP-CSNP），并对其稳定性增强进行了研究。HRP-CSNP在37°C下于变性剂尿素存在的情况下保留了酶活性并具有更高的稳定性。这些纳米颗粒有效地结合到人乳腺癌细胞Bcap37的表面，当与前药吲哚-3-乙酸一起应用时导致超过80%的细胞死亡。
