Toward Gene Therapy of Hypertension: Experimental Study on Hypertensive ISIAH Rats

Area of Science:

• Biomaterials Science
• Nanotechnology
• Pharmacology

Background:

• Hypertension remains a leading cause of cardiovascular disease, necessitating innovative therapeutic strategies.
• Gene therapy offers a targeted approach to disease treatment, but efficient delivery remains a challenge.
• Titanium dioxide (TiO2) nanoparticles present a potential platform for drug and gene delivery applications.

Purpose of the Study:

• To develop and evaluate TiO2-based nanocomposites for targeted oligonucleotide delivery.
• To investigate the efficacy of these nanocomposites in a rat model of stress-sensitive arterial hypertension.
• To assess the potential of TiO2-based nanocomposites for treating hypertensive disease.

Main Methods:

• Preparation of TiO2-nanoparticles immobilized with polylysine-containing oligonucleotides (TiO2·PL-DNA).
• Administration of nanocomposites via intraperitoneal injection and inhalation in ISIAH hypertensive rats.
• Measurement of systolic blood pressure changes and assessment of ACE1 mRNA targeting.

Main Results:

• TiO2·PL-DNA nanocomposites successfully delivered gene-targeted oligonucleotides into cells.
• Administration of nanocomposites containing ACE1 gene-targeted oligonucleotides resulted in a significant 20-30 mm Hg decrease in systolic blood pressure.
• Oligonucleotides with random sequences showed no significant effect on blood pressure.

Conclusions:

• TiO2-based nanocomposites are effective for delivering gene-targeting oligonucleotides for potential hypertension treatment.
• Targeted delivery of ACE1 gene-modulating oligonucleotides via TiO2 nanocomposites offers a promising therapeutic strategy for hypertension.
• Inhalation delivery of these nanocomposites warrants further development for clinical applications in managing systemic hypertensive disease.