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题名: Highly flexible and stable aptamer-caged nanoparticles for control of thrombin activity
作者: Chia-Lun Hsu
Shih-Chun Wei
Jyun-Wei Jian
Huan-Tsung Chang
Wei-Hsi Chen
Chih-Ching Huang
贡献者: 國立臺灣海洋大學:生命科學暨生物科技學系
日期: 2012
上传时间: 2016-09-08T01:26:07Z
出版者: RSC Advances
摘要: Abstract: In this paper, we have demonstrated that the thymine linker length number (Tn, n = 0–60) and stem pair number (Pm, m = 0–16) in the terminal of thrombin binding aptamers (TBAs) have a strong impact on the flexibility and stability of TBA-modified gold nanoparticles (TBA–Au NPs) and thus the binding strength and inhibitory potency toward thrombin. The anticoagulation of TBA–Au NPs increased with an increase in the linker length from T0 to T30 due to an increase in the flexibility of G-quadruplexes of TBAs on the Au NP surfaces (TBA-Tn–Au NPs). The inhibition of TBA-PmT15–Au NPs increased with an increase in the Pm from P0 to P8 as a result of the increase in the rigidity and the stability of G-quadruplexes of the TBAs on the Au NP surfaces. The best results were observed for multivalent TBA–Au NPs conjugates—TBA15/TBA29-P8T15–Au NPs—which exhibited ultra-high binding affinity toward thrombin (Kd = 8.86 × 10−12 M) and thus extremely high anticoagulant (inhibitory) potency because of their particularly flexible and stable conformation and multivalency. Compared to the case without inhibitors, their measured thrombin clotting time (TCT) was 296 times longer, whereas for TBA15 alone it was only 3.9 times longer. From the dosage dependence of the TCT delay, we further demonstrated the anticoagulation ability of our TBA15/TBA29-P8T15–Au NPs was much better than the commercial drugs (argatroban and hirudin). Moreover, the Au NPs modified with TBA with photocleavable (PC) units allow a reversal in the activity of TBAPC–Au NPs via near-UV light-inducement of TBA release from Au NPs. We believe that our described techniques can be used widely to modify NPs with other anticoagulant DNA or RNA aptamers towards different proteins such as factor IX, activated protein C, and factor VIIa.
關聯: 4
URI: http://ntour.ntou.edu.tw:8080/ir/handle/987654321/38502
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