Programmable Peptide-Cross-Linked Nucleic Acid Nanocapsules as a Modular Platform for Enzyme Specific Cargo Release

Area of Science:

• Biotechnology and Nanomedicine
• Molecular Engineering
• Bioconjugation Chemistry

Background:

• Developing targeted drug delivery systems requires precise control over cargo release.
• Nanocapsules offer a versatile platform for encapsulating and delivering therapeutic agents.
• Enzyme-responsive systems are crucial for triggered release mechanisms in biological environments.

Purpose of the Study:

• To establish a modular assembly strategy for photo-cross-linking peptides into nucleic acid functionalized nanocapsules.
• To engineer nanocapsules capable of enzyme-triggered cargo release.
• To evaluate the specificity and potential applications of these nanocapsules in biosensing and drug delivery.

Main Methods:

• Modular assembly of nanocapsules using photocatalyzed thiol-yne chemistry for peptide cross-linking.
• Incorporation of enzyme-cleavable peptide linkers within the nanocapsule structure.
• Screening of nanocapsules against various proteases in vitro and in cell culture.
• Characterization using fluorescence assays, confocal microscopy, and transmission electron microscopy (TEM).

Main Results:

• Successful incorporation of diverse peptide cross-linkers into nanocapsules via photo-cross-linking.
• Demonstrated enzyme-specific gating and triggered release of molecular and nanoscale cargo.
• High specificity observed for target proteases, distinguishing between enzymes of similar classes.
• Validation of nanocapsule function in both in vitro and cell culture settings.

Conclusions:

• The developed modular assembly strategy enables efficient photo-cross-linking of peptides into nanocapsules.
• These nanocapsules provide a highly specific, enzyme-triggered mechanism for cargo release.
• The system shows significant potential for advanced intracellular and extracellular biosensing and targeted drug delivery applications.