circNCX1-nanogel mitigates radiation-induced heart disease

Area of Science:

• Cardiology
• Molecular Biology
• Biotechnology

Background:

• Radiation-induced heart disease (RIHD) is a serious complication of thoracic radiotherapy.
• The molecular mechanisms of RIHD are not fully understood, and effective treatments are limited.
• Circular RNAs (circRNAs) are emerging as key regulators in cellular processes.

Purpose of the Study:

• To investigate the role of circNCX1 in radiation-induced heart disease.
• To develop a novel nanogel delivery system for circNCX1 to treat RIHD.
• To evaluate the therapeutic efficacy of circNCX1 nanogel in preclinical models.

Main Methods:

• In vitro studies using human cardiomyocyte AC16 cells exposed to X-ray irradiation.
• Development of a cardiac-targeted circNCX1-nanogel using polyethylene glycol-sodium alginate matrix.
• In vivo studies in C57BL/6J mice subjected to localized heart irradiation.

Main Results:

• Radiation exposure inhibited circNCX1 expression in cardiomyocytes.
• CircNCX1 acts as a competing endogenous RNA (ceRNA) for miR-133a-3p, regulating PIK3C2A and the PI3K/AKT/mTOR pathway.
• Intravenous administration of circNCX1 nanogel prior to irradiation significantly preserved cardiac function, reduced fibrosis and apoptosis in mice.
• No significant off-target organ injury was detected.

Conclusions:

• CircNCX1 plays a protective role against radiation-induced cardiomyocyte apoptosis and dysfunction.
• Cardiac-targeted circNCX1 nanogel is a promising therapeutic strategy for mitigating RIHD.
• Pre-irradiation administration of circNCX1 nanogel offers robust cardioprotection.