Thrombotic microenvironment responsive crosslinking cyclodextrin metal-organic framework nanocarriers for precise...

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Pharmacology

Background:

• Thrombotic disorders pose a significant global health threat due to high mortality and disability rates.
• Existing thrombolytic agents often have short circulation half-lives, limiting their therapeutic effectiveness.
• Targeted drug delivery systems are crucial for precise and regulated release of therapeutics at thrombus sites.

Purpose of the Study:

• To develop an intelligent drug delivery system (MCRUA) for targeted thrombolysis.
• To enable precise drug release triggered by the thrombus microenvironment.
• To combine thrombolytic and anti-inflammatory actions for enhanced treatment of thrombotic disorders.

Main Methods:

• Development of a metal-organic framework (MC) system loaded with urokinase-type plasminogen-activator (uPA) and aspirin (ASA).
• Functionalization of the MC surface with c(RGD) for platelet targeting.
• Utilizing pH-sensitive CaCO3/cyclodextrin crosslinking for controlled drug release in acidic thrombus environments.

Main Results:

• The MCRUA system selectively targets platelets and disintegrates in acidic thrombus microenvironments.
• Controlled release of uPA promotes thrombolysis and vessel recanalization.
• Encapsulated ASA reduces inflammation and enhances antiplatelet aggregation, supporting cooperative therapy.

Conclusions:

• The MCRUA drug delivery system effectively promotes thrombolysis and suppresses rethrombosis in thrombotic disorders.
• This system offers enhanced biosafety with a reduced risk of hemorrhagic side effects.
• MCRUA represents a promising strategy for advanced, targeted treatment of thrombotic conditions.