Photodynamic Treatment of Acute Vascular Occlusion by Using Iron–nitrosyl Complex

Abstract
Retinal vascular occlusion (RVO) is a common cause of visual impairment. Although several approaches, including vasodilators, have been explored to treat retinal vascular occlusion, there is no proper method to treat this obstruction today. We report a strategy that aims to pierce clogged blood vessels with a spatiotemporally controllable nitric oxide transporter, [Fe(TBDAP)(NO)(H2O)]2+ (1), which was synthesized and precisely characterized by various physicochemical methods, including X-ray crystallography. In the animal model, normal retinal blood vessels were confirmed to be dilated by the photoresponsive iron–nitrosyl complex. Furthermore, occluded retinal blood vessels were effectively reperfused after the immediate delivery of nitric oxide using light in animal disease models. These studies suggest an unprecedentedly selective and controllable treatment option for acute vascular occlusive diseases, including cardiovascular and cerebrovascular diseases.

Blood flowing through the blood vessels carries oxygen, nutrients and waste around the body. Obstruction of a blood vessel in our body can cause severe organ damage. In particular, retinal vascular occlusion (RVO) is a common cause of visual impairment. Although several conventional vasodilators and thrombolytic agents have previously been considered as treatment, their clinical applications to vascular diseases are limited mainly because of slow reaction time and lack of precise control of their actions, noted the research team.

A research team, led by Professor Jaeheung Cho in the Department of Chemistry at UNIST, in collaboration with Professor Junyeop Lee (Department of Ophthalmology, Asan Medical Center), and Professor Mu-Hyun Baik (Department of Chemistry, KAIST) has unveiled a promising therapeutic option for treating RVO disorders. In this study, they reported a strategy that aims to pierce clogged blood vessels with a spatiotemporally controllable nitric oxide transporter, [Fe(TBDAP)(NO)(H2O)]2+ (1), which was synthesized and precisely characterized by various physicochemical methods, including X-ray crystallography. According to the research team, their findings suggest an unprecedentedly selective and controllable treatment option for acute vascular occlusive diseases, including cardiovascular and cerebrovascular diseases.

Figure 1. The NO delivery with temporal and spatial control by a photodissociable iron–nitrosyl complex.

Their findings showed that normal retinal blood vessels were confirmed to be dilated by the photoresponsive iron–nitrosyl complex in the animal model. Furthermore, occluded retinal blood vessels were effectively reperfused after the immediate delivery of nitric oxide using light in animal disease models, noted the research team. These studies suggest an unprecedentedly selective and controllable treatment option for acute vascular occlusive diseases, including cardiovascular and cerebrovascular diseases.

This study has been jointly participated by Jisu Choe from the Department of Chemistry at UNIST, Soo Jin Kim from Asan Medical Center, and Jun-Hyeong Kim from KAIST, as first co-authors. This study has been supported by the National Research Foundation of Korea (NRF), funded by the Ministry of Science and ICT (MSIT), and the Institute for Basic Science in Korea.

Journal Reference
Jisu Choe, Soo Jin Kim, Jun-Hyeong Kim, et al., “Photodynamic treatment of acute vascular occlusion by using an iron–nitrosyl complex,” Chem (2023)