pH-Dependent nanostructure based on isoquinoline-cyclodextrin conjugate for thrombosis therapy

Area of Science:

• Bioconjugation chemistry
• Nanomaterial science
• Pharmacology

Background:

• Thrombotic diseases pose significant clinical challenges.
• Development of effective oral antithrombotic agents is crucial.
• 3S-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (THIQA) is a potential therapeutic scaffold.

Purpose of the Study:

• To synthesize and characterize a novel antithrombotic agent by modifying THIQA with beta-cyclodextrin (β-CD).
• To investigate the pH-dependent nanostructure formation of the conjugate.
• To evaluate the in vitro and in vivo antithrombotic efficacy and stability of the conjugate.

Main Methods:

• Chemical modification of THIQA with β-CD to form THIQA-β-CD.
• Characterization of nanostructures using techniques sensitive to size and morphology.
• Assessment of pH-dependent structural changes in aqueous solutions.
• In vitro evaluation of inhibition of thrombin-induced platelet aggregation.
• In vivo assessment of antithrombotic efficacy.

Main Results:

• Successful synthesis of THIQA-β-CD, an oral antithrombotic agent.
• Formation of pH-dependent nanostructures: nanoclouds (pH 3.0), nanorods (pH 7.2), and nanowires (pH 10.1).
• Demonstrated enhanced stability in blood.
• Significant inhibition of platelet aggregation in vitro.
• Confirmed antithrombotic efficacy in vivo.

Conclusions:

• Modification of THIQA with β-CD yields a promising oral antithrombotic agent (THIQA-β-CD).
• The pH-dependent nanostructures contribute to the conjugate's stability and efficacy.
• This approach offers a viable strategy for the clinical therapy of thrombus disease.