Enhanced Secretion of Functional Insulin with DNA-Functionalized Gold Nanoparticles in Cells

Area of Science:

• Biotechnology
• Nanomedicine
• Molecular Biology

Background:

• Gold nanoparticles (AuNPs) functionalized with DNA (AuNP-DNA) previously enhanced insulin mRNA translation in cell-free systems.
• Translating this to a whole-cell system presents challenges in intracellular delivery and regulation of mRNA translation.

Purpose of the Study:

• To demonstrate the functionality of AuNP-DNA in a whole-cell system for enhancing insulin secretion.
• To investigate the stability, toxicity, and efficacy of AuNP-insDNA in insulin-secreting cells.

Main Methods:

• Conjugation of a DNA oligomer (insDNA) complementary to insulin mRNA's 3'-UTR to AuNPs, forming AuNP-insDNA.
• Incubation of AuNP-insDNA with RIN-5F pancreatic islet cells and assessment of stability and toxicity.
• Measurement of insulin secretion and functionality post-incubation with AuNP-insDNA.

Main Results:

• AuNP-insDNA remained stable and non-toxic in RIN-5F cells for 24 hours.
• AuNP-insDNA significantly enhanced insulin secretion between 6-12 hours, peaking at 10 hours with a 1.69-fold increase.
• The observed enhancement was sequence-specific to insDNA, and the secreted insulin was fully functional.

Conclusions:

• AuNP-DNA conjugates are feasible for enhancing protein synthesis in whole cells.
• This technology offers a potential new strategy for diabetes treatment by stimulating endogenous insulin secretion.