Chemiexcited Photodynamic Therapy Integrated in Polymeric Nanoparticles Capable of MRI Against Atherosclerosis

化学激发光动力疗法集成于聚合物纳米粒子中,可用于 MRI 治疗动脉粥样硬化

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作者:Dan Mu #, Xin Wang #, Huiting Wang, Xuan Sun, Qing Dai, Pin Lv, Renyuan Liu, Yu Qi, Jun Xie, Biao Xu, Bing Zhang

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.

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.

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.

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