Dan Mu1, Xin Wang1, Huiting Wang1, Xuan Sun2, Qing Dai2, Pin Lv1, Renyuan Liu1, Yu Qi2, Jun Xie2, Biao Xu2,3, Bing Zhang1,4. 1. Department of Radiology, Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School, Nanjing, 210008, People's Republic of China. 2. Department of Cardiology, Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School, Nanjing, 210008, People's Republic of China. 3. State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, Jiangsu, 210023, People's Republic of China. 4. Institute of Brain Science, Nanjing University, Nanjing, Jiangsu, 210008, People's Republic of China.
Abstract
Background: Photodynamic therapy (PDT) has achieved continued success in the treatment of tumors, but its progress in the treatment of atherosclerosis has been limited, mainly due to the low tissue-penetration ability of the excitation light for photosensitizers. Methods: In this study, we designed a chemiexcited system producing singlet oxygen in an attempt to apply PDT for the treatment of atherosclerosis without the irradiation of external light. The system designed was polymeric nanoparticles (NPs) equipped with chemical fuel and photosensitizers, cross-linked with an Fe3+-catechol complex for stabilization and magnetic resonance imaging (MRI). Results: The system (FeCNPs for short) accumulated effectively in plaques, providing persistent and enhanced T 1-weighted contrast ability. FeCNPs also prevented progression of atherosclerosis via macrophage elimination, and obviously reduced plaque size and thickness revealed by T 1-weighted MRI. Expression of CD68, MCP1, and TNFα was significantly reduced after treatment. However, low doses of FeCNPs exhibited better therapeutic efficacy than high doses. Furthermore, low-dose FeCNPs exhibited effective macrophage elimination in aortic arches and abdominal aortae, but inefficiency in the thoracic aorta, aortic hiatus, and aorta-iliac bifurcation. Conclusion: This study provides the first example of a combination of MRI and chemiexcited PDT for atherosclerosis, evidencing the effectiveness of PDT and providing significant pointers for developing nanotherapy on atherosclerosis.
Background: Photodynamic therapy (PDT) has achieved continued success in the treatment of tumors, but its progress in the treatment of atherosclerosis has been limited, mainly due to the low tissue-penetration ability of the excitation light for photosensitizers. Methods: In this study, we designed a chemiexcited system producing singlet oxygen in an attempt to apply PDT for the treatment of atherosclerosis without the irradiation of external light. The system designed was polymeric nanoparticles (NPs) equipped with chemical fuel and photosensitizers, cross-linked with an Fe3+-catechol complex for stabilization and magnetic resonance imaging (MRI). Results: The system (FeCNPs for short) accumulated effectively in plaques, providing persistent and enhanced T 1-weighted contrast ability. FeCNPs also prevented progression of atherosclerosis via macrophage elimination, and obviously reduced plaque size and thickness revealed by T 1-weighted MRI. Expression of CD68, MCP1, and TNFα was significantly reduced after treatment. However, low doses of FeCNPs exhibited better therapeutic efficacy than high doses. Furthermore, low-dose FeCNPs exhibited effective macrophage elimination in aortic arches and abdominal aortae, but inefficiency in the thoracic aorta, aortic hiatus, and aorta-iliac bifurcation. Conclusion: This study provides the first example of a combination of MRI and chemiexcited PDT for atherosclerosis, evidencing the effectiveness of PDT and providing significant pointers for developing nanotherapy on atherosclerosis.
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