Biodegradable Microrobots for DNA Vaccine Delivery.

Area of Science:

• Biomaterials Science
• Nanotechnology
• Immunology

Background:

• Nucleic acid vaccines, including DNA vaccines, show potential for stimulating immune responses against diseases like Coronavirus disease 2019.
• Current limitations of nucleic acid vaccines include rapid clearance and poor cellular uptake, hindering their therapeutic efficacy.
• Microrobots present an opportunity to overcome these limitations by controlling vaccine release and cellular interactions.

Purpose of the Study:

• To develop biocompatible and biodegradable microrobots for enhanced DNA vaccine delivery.
• To investigate the controlled degradation and release of DNA vaccines from fabricated microrobots.
• To evaluate the in vivo immune response and antigen expression elicited by microrobot-delivered DNA vaccines.

Main Methods:

• Fabrication of microrobots using two-photon polymerization of gelatin methacryloyl (GelMA).
• Functionalization of GelMA microspheres with polyethyleneimine for DNA vaccine complexation.
• Assessment of programmed degradation and drug release kinetics via 3D laser lithography.
• In vivo studies in mice to evaluate antigen expression and immune response.
• Fabrication of magnetically maneuverable GelMA microrobots.

Main Results:

• Successful 3D fabrication of biocompatible and biodegradable GelMA microrobots.
• Demonstrated programmed degradation and controlled DNA release by varying laser exposure.
• Functionalized microrobots effectively delivered DNA vaccines to dendritic cells and primary cells.
• Microrobot-delivered DNA vaccines in mice resulted in enhanced, rapid, and durable antigen expression.
• Magnetically guided GelMA microrobots were successfully fabricated.

Conclusions:

• GelMA microrobots provide a novel platform for efficient DNA vaccine delivery.
• This approach enhances antigen expression duration, potentially leading to prolonged protective immunity.
• Microrobot technology offers a promising strategy for improving the efficacy of nucleic acid vaccines.