Background Arterial thrombosis has been associated with a series of pathological conditions, and the discovery of arterial thrombosis inhibitor is of clinical importance. Methods 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. Results 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. Conclusion 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.

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Thrombosis seriously threatens human health worldwide. Tetrahydroisoquinoline-3-carboxylic acid (IQCA) is an antithrombotic agent, while Thr-Ala-Arg-Gly-Asp(Ser)-Ser (TASS) can target thrombus. In the discovery of nano-delivery system for targeting thrombus tetrahydroisoquinoline-3-carbonyl-Thr-Ala-Arg-Gly-Asp(Ser)-Ser (IQCA-TASS) was designed here. In vitro IQCA-TASS acted on P-selectin and down-regulated P-selectin expression. The IC 50 values of IQCA-TASS against the platelet aggregation induced by four aggregators were less than 0.45 nM.In vivo IQCA-TASS targeted thrombus, released IQCA and TASS inside thrombus, showed dose-dependent anti-thrombotic action, of which the minimal effective dose was 1 nmol/kg, and showed anti-inflammatory action. Even the dose been up to 1 μmol/kg, a dose of 1000 times of the minimal effective dose, IQCA-TASS still induced no toxic reaction. In rat plasma IQCA-TASS forms the nanoparticles of less than 41 nm in diameter. The interactions of the nanoparticles with both resting and activated platelets were imaged. In conclusion, IQCA-TASS should be a safe nano-medicine capable of targeting thrombus and releasing the anti-thrombotic/anti-inflammatory pharmacophores in the disease site.