Fluorinated Guanidino-Polyamine Conjugates with Ribonuclease Activity - Toward a Therapeutic Tool for Multi-Drug...

Area of Science:

• Biomaterials Science
• Nanotechnology
• Gene Therapy

Background:

• Developing multifunctional carriers is crucial for advanced therapeutics, especially for multi-drug therapy (MDT).
• Existing gene delivery systems face challenges in efficiency and multifunctionality.

Purpose of the Study:

• To synthesize and characterize novel fluorinated guanidino-polyamine conjugates for dual gene delivery and RNA degradation.
• To evaluate their potential as theranostic agents for combined diagnostics and MDT.

Main Methods:

• Synthesis of fluorinated guanidino-polyamine conjugates using polyamidoamine (PAMAM) dendrimers and polyethyleneimine (PEI).
• Potentiometric, kinetic, biolayer interferometry, and transfection studies to assess catalytic activity and gene delivery efficiency.
• ¹⁹F MRI for tracking capabilities.

Main Results:

• Conjugates demonstrated efficient DNA condensation and intracellular delivery.
• Proven mRNA cleavage activity, leading to reduced gene expression.
• High plasmid DNA (pDNA) delivery efficiency with low cytotoxicity, outperforming conventional PEI systems.

Conclusions:

• Low-generation PAMAM-derived conjugates exhibit potent artificial ribonuclease and gene delivery capabilities.
• These multifunctional carriers show promise for synergistic gene delivery and RNA degradation in MDT.
• The developed conjugates offer a novel strategy for combined diagnostic and therapeutic applications.