Dual-Responsive Enzyme-Polysaccharide Conjugate as a Nanocarrier System for Enzyme Prodrug Therapy

Area of Science:

• Nanomedicine
• Bioconjugation
• Drug Delivery Systems

Background:

• Biopolymer-based systems are crucial for advanced drug delivery.
• Enzyme-prodrug therapy offers targeted cancer treatment strategies.
• Horseradish peroxidase (HRP) and acetalated dextran (AcDex) are key biomaterials.

Purpose of the Study:

• To synthesize and characterize a novel HRP-AcDex bioconjugate.
• To evaluate its dual-responsive drug release capabilities.
• To investigate its potential in enzyme prodrug therapy for cancer.

Main Methods:

• Covalent conjugation of HRP and AcDex via thiol exchange.
• Formation of amphiphilic self-assembled nanoparticles.
• Encapsulation of indole-3-acetic acid (IAA) prodrug.
• Assessment of dual-responsive release in acidic and reductive conditions.
• Evaluation of HRP-mediated prodrug activation and cytotoxicity.

Main Results:

• Successful synthesis of the HRP-AcDex bioconjugate.
• Demonstration of dual-responsive (acidic/reductive) micellar nanoparticle disassembly.
• Controlled release and HRP-catalyzed activation of IAA prodrug.
• Induction of cellular apoptosis, indicating therapeutic potential.

Conclusions:

• The HRP-AcDex bioconjugate effectively delivers and activates the IAA prodrug.
• This system shows promise for a novel enzyme prodrug therapy against cancer.
• Dual-responsive nanomedicine offers a platform for targeted cancer treatment.