International Journal of Nanomedicine (May 2022)

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

  • Mu D,
  • Wang X,
  • Wang H,
  • Sun X,
  • Dai Q,
  • Lv P,
  • Liu R,
  • Qi Y,
  • Xie J,
  • Xu B,
  • Zhang B

Journal volume & issue
Vol. Volume 17
pp. 2353 – 2366

Abstract

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Dan Mu,1,* Xin Wang,1,* Huiting Wang,1 Xuan Sun,2 Qing Dai,2 Pin Lv,1 Renyuan Liu,1 Yu Qi,2 Jun Xie,2 Biao Xu,2,3 Bing Zhang1,4 1Department of Radiology, Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School, Nanjing, 210008, People’s Republic of China; 2Department of Cardiology, Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School, Nanjing, 210008, People’s Republic of China; 3State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, Jiangsu, 210023, People’s Republic of China; 4Institute of Brain Science, Nanjing University, Nanjing, Jiangsu, 210008, People’s Republic of China*These authors contributed equally to this workCorrespondence: Biao Xu; Bing Zhang, Email [email protected]; [email protected]: 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 T1-weighted contrast ability. FeCNPs also prevented progression of atherosclerosis via macrophage elimination, and obviously reduced plaque size and thickness revealed by T1-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.Keywords: photodynamic therapy, atherosclerosis, chemi-excited, macrophages, MRI

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