A CD36-targeted aptamer-4-butyl-polyhydroxybenzophenone conjugate with pH-responsive release for liver delivery in...

Area of Science:

• Biomedical Engineering
• Drug Delivery
• Hepatology

Background:

• Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent global health issue requiring effective treatments.
• Aptamers offer advantages over antibodies for targeted drug delivery due to their small size and low immunogenicity.

Purpose of the Study:

• To develop and evaluate a novel aptamer-drug conjugate (ApDC) for targeted delivery in MASLD.
• To assess the efficacy of the CD36-targeted ApDC, ASC, in preclinical MASLD models.

Main Methods:

• Conjugation of the NAFLD01 aptamer with the therapeutic compound SF to create ASC.
• In vivo studies using high-fat diet-induced MASLD mice to evaluate ASC's therapeutic effects.
• In vitro studies using MASLD cell models to assess ASC's impact on lipid accumulation and cellular injury.

Main Results:

• SF treatment significantly reduced body weight, liver injury, and lipid accumulation in MASLD mice.
• ASC effectively decreased lipid droplets and hepatic injury markers while enhancing antioxidant enzymes in MASLD cell models.
• ASC demonstrated targeted delivery of SF, high binding affinity, and efficient cellular uptake, with drug release in acidic lysosomal environments.

Conclusions:

• ASC represents a promising aptamer-drug conjugate delivery platform for MASLD.
• Targeted delivery via ASC potentially minimizes off-target effects of the therapeutic compound.
• The study highlights the therapeutic potential of aptamer-based targeted delivery systems for MASLD.