Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, Engineering Research Center of Endogenous Prophylactic of Ministry of Education of China, Beijing, China.
Beijing Laboratory of Biomedical Materials, College of Pharmaceutical Sciences, Capital Medical University, Beijing, China.
Int J Nanomedicine. 2018 Feb 26;13:1139-1158. doi: 10.2147/IJN.S150205. eCollection 2018.
Arterial thrombosis has been associated with a series of pathological conditions, and the discovery of arterial thrombosis inhibitor is of clinical importance.
By analyzing the pharmacophores of anti-platelet agents, thrombus targeting peptide and anti-thrombotic nano-systems 3S-1,2,3,4-tetrahydroisoquino-line-3-carbonyl-Thr-Ala-Arg-Gly-Asp(Val)-Val (IQCA-TAVV) was designed and prepared as a nano-scaled arterial thrombosis inhibitor.
In vitro the nanoparticles of IQCA-TAVV were able to adhere onto the surface of activated platelets, attenuate activated platelets to extend pseudopodia and inhibit activated platelets to form aggregators. In vivo IQCA-TAVV targeted arterial thrombus, dose dependently inhibited arterial thrombosis with a 1 nmol/kg of minimal effective dose, and the activity waŝ1670 folds of that of aspirin.
IQCA-TAVV represented the design, preparation and application of nanomedicine capable of adhering on the surface of activated platelets, attenuating platelet activation, targeting arterial thrombus and inhibiting arterial thrombosis.
动脉血栓形成与一系列病理状况有关，因此发现动脉血栓抑制剂具有重要的临床意义。
通过分析抗血小板药物、血栓靶向肽和抗血栓纳米系统 3S-1,2,3,4-四氢异喹啉-3-甲酰基-Thr-Ala-Arg-Gly-Asp(Val)-Val（IQCA-TAVV）的药效团，设计并制备了纳米级动脉血栓抑制剂 IQCA-TAVV。
体外实验中，IQCA-TAVV 纳米颗粒能够黏附在活化血小板表面，抑制活化血小板延伸伪足，并抑制活化血小板形成聚集物。在体内，IQCA-TAVV 靶向动脉血栓，以 1nmol/kg 的最小有效剂量剂量依赖性地抑制动脉血栓形成，其活性是阿司匹林的 1670 倍。
IQCA-TAVV 代表了能够黏附在活化血小板表面、抑制血小板活化、靶向动脉血栓和抑制动脉血栓形成的纳米医学的设计、制备和应用。
