Modified Stability of microRNA-Loaded Nanoparticles

Area of Science:

• Biotechnology
• Nanomedicine
• Drug Delivery

Background:

• MicroRNAs (miRNAs) show therapeutic potential for diseases like diabetes mellitus.
• Efficient delivery of miRNAs remains a significant challenge in their clinical application.
• Self-assembled miRNA-protein nanoparticles offer a promising strategy to overcome delivery obstacles.

Purpose of the Study:

• To functionalize binary miRNA-protamine nanoparticles (proticles) with citric acid.
• To reduce the binding strength between miRNA and protamine for improved dissociation.
• To investigate the impact of citric acid on proticle colloidal stability, size, and drug loading.

Main Methods:

• Formation of proticles by combining miRNA with protamine.
• Functionalization of proticles with citric acid.
• Analysis of colloidal stability, particle size distribution, and drug loading.
• Atomic Force Microscopy (AFM) for structural investigation.
• In vitro assessment of cellular toxicity and uptake pathways.

Main Results:

• Citric acid functionalization influenced colloidal stability and maintained constant particle size and monodisperse distribution.
• Citric acid addition increased miRNA drug loading capacity.
• AFM revealed loosely complexed nanoparticles, with citric acid altering their shape.
• Reduced binding affinity and nanoparticulate stability were observed.
• Low cellular toxicity and consistent cellular uptake were demonstrated.

Conclusions:

• Citric acid functionalization is a viable strategy to modulate miRNA-protamine nanoparticle properties.
• The modification facilitates controlled miRNA release by reducing binding affinity.
• The developed nanoparticles exhibit favorable characteristics for potential therapeutic delivery, including low toxicity and effective cellular uptake via active and passive routes.