Encapsulation and Ultrasound-Triggered Release of G-Quadruplex DNA in Multilayer Hydrogel Microcapsules

Area of Science:

• Biomaterials Science
• Drug Delivery Systems
• Nucleic Acid Therapeutics

Background:

• Nucleic acids offer precise disease treatment but are vulnerable to degradation in the body.
• Developing effective delivery systems is crucial for realizing the therapeutic potential of nucleic acids.

Purpose of the Study:

• To create stimuli-responsive multilayer hydrogel capsules for protecting and delivering nucleic acid therapeutics.
• To demonstrate controlled release of G-quadruplex DNA and double-stranded DNA from these capsules.

Main Methods:

• Fabrication of poly(methacrylic acid)/poly(N-vinylpyrrolidone) (PMAA/PVPON)n multilayer hydrogel capsules.
• Encapsulation of ~7 kDa G-quadruplex DNA and ~450 kDa double-stranded DNA.
• Assessment of on-demand DNA release triggered by enzymatic degradation and ultrasound (US).

Main Results:

• The hydrogel capsules successfully encapsulated and protected both small and large DNA molecules.
• Controlled release of DNA was achieved in response to enzymatic and US stimuli.
• The G-quadruplex DNA's functional basket conformation was preserved post-release.

Conclusions:

• The developed (PMAA/PVPON)n hydrogel capsules offer a promising method for delivering sensitive nucleic acid biomolecules.
• This technology can advance therapeutic strategies for DNA vaccines, immunotherapies, cancer, and tissue regeneration.