Nucleic Acid Nanocapsules for Enzyme-Triggered Drug Release

Area of Science:

• Nanotechnology
• Bioconjugate Chemistry
• Materials Science

Background:

• Development of advanced drug delivery systems is crucial for targeted and efficient therapeutic interventions.
• Nanocapsules offer a versatile platform for encapsulating and delivering various therapeutic agents.
• Enzyme-responsive materials are desirable for controlled drug release and degradation.

Purpose of the Study:

• To design and characterize a novel nucleic acid-functionalized nanocapsule system.
• To investigate the enzyme-triggered assembly/disassembly and degradation properties of the nanocapsules.
• To explore the potential of these nanocapsules for therapeutic applications, including loading and surface functionalization.

Main Methods:

• Synthesis of ester cross-linked nanocapsules with hydrophobic loading capabilities.
• Copper-catalyzed click chemistry for post-assembly covalent cross-linking.
• UV-light-mediated thiolyne chemistry for DNA functionalization.
• Enzyme-mediated functionalization with mRNA-cleaving DNAzyme.

Main Results:

• The nanocapsules are fully degradable in response to esterases.
• Successful loading of hydrophobic small molecules and covalent cross-linking were achieved.
• Thiolated DNA and mRNA-cleaving DNAzyme were successfully conjugated to the nanocapsule surface.
• The resulting nanocapsules exhibit high stability and monodisperse size distribution.

Conclusions:

• A novel, degradable nanocapsule platform has been developed with versatile functionalization capabilities.
• The nanocapsules demonstrate enzyme responsiveness and stability, suitable for therapeutic applications.
• This system maximizes the therapeutic potential by utilizing both the interior and exterior of the nanocapsule.