Reactive oxygen species responsive double-locked liposome collaborative photodynamic therapy for reducing electrical conduction recurrence after radiofrequency catheter ablation

Ying Zhuge; Gonghao Li; Mingyue Sun; Jiajia Zhang; Jiafeng Zou; Feng Gao; Fang Wang

International Journal of Pharmaceutics: X (Dec 2024)

Reactive oxygen species responsive double-locked liposome collaborative photodynamic therapy for reducing electrical conduction recurrence after radiofrequency catheter ablation

Ying Zhuge,
Gonghao Li,
Mingyue Sun,
Jiajia Zhang,
Jiafeng Zou,
Feng Gao,
Fang Wang

Affiliations

Ying Zhuge: Department of Cardiology, Shanghai General Hospital of Nanjing Medical University, Shanghai 200800, China; Department of Cardiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200800, China
Gonghao Li: Department of Cardiology, Shanghai General Hospital of Nanjing Medical University, Shanghai 200800, China; Department of Cardiology, Lianyungang Clinical College of Nanjing Medical University, Lianyungang 222000, China
Mingyue Sun: Shanghai Frontier Science Center of Optogenetic Techniques for Cell Metabolism, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China
Jiajia Zhang: Shanghai Frontier Science Center of Optogenetic Techniques for Cell Metabolism, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China
Jiafeng Zou: Shanghai Frontier Science Center of Optogenetic Techniques for Cell Metabolism, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China
Feng Gao: Shanghai Frontier Science Center of Optogenetic Techniques for Cell Metabolism, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China; Shanghai Key Laboratory of Functional Materials Chemistry, East China University of Science and Technology, Shanghai 200237, China; Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China; Optogenetics and Synthetic Biology Interdisciplinary Research Center, State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China; Corresponding author at: Shanghai Frontier Science Research Base of Optogenetic Techniques for Cell Metabolism, School of Pharmacy, East China University of Science and Technology, 130 Meilong Road, Shanghai 200237. China.
Fang Wang: Department of Cardiology, Shanghai General Hospital of Nanjing Medical University, Shanghai 200800, China; Department of Cardiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200800, China; Corresponding author at: Department of Cardiology, Shanghai General Hospital of Nanjing Medical University, Shanghai 200800, China.

Journal volume & issue: Vol. 8
p. 100275

Abstract

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Radiofrequency catheter ablation (RFCA) is the preferred technique for the treatment of atrial fibrillation, but the recovery of electrical conduction after ablation seriously endangers the health of patients. This study aimed to develop reactive oxygen species (ROS) responsive double-locked liposome collaborative photodynamic therapy (PDT) to target the ablation area and reduce the recovery of electrical conduction after ablation. The successful synthesis of β-cyclodextrin modified with phenylboronic acid pinacol ester (OCD) was confirmed by 1H NMR and FT-IR. Furthermore, the successful synthesis of octadecylamine-modified indocyanine green (ICG-ODA) was confirmed by 1H NMR and mass spectrometry. The ICG-ODA was encapsulated in liposomes to generate a double-locked hybrid liposome (ICG-ODA@rNP), which was subsequently characterized. Several properties of ICG-ODA@rNP were evaluated, including the drug release, targeting ability and ability to inhibit electrical conduction recurrence. Moreover, a model was constructed for the blockage of electrical conduction after RFCA in rabbits to further evaluate ICG-ODA@rNP. The preliminary safety evaluation of ICG-ODA@rNP was also performed. The ICG-ODA@rNP with a uniform particle size showed excellent storage stability. The nanoparticle can sensitively release drugs under ROS environment, and exhibits excellent photothermal effects. Furthermore, ICG-ODA@rNP can circulate for a long time in vivo and accumulate significantly in the ablation area. In a pacing test with a left atrial appendage (LAA), these nanoparticles, combined with PDT, reduced the ratio of electrical conduction recovery, which was confirmed by a hematoxylin and eosin (H&E) test. Further molecular analysis revealed that ICG-ODA@rNP could increase RFCA-induced apoptosis and ROS levels. Specifically, ICG-ODA@rNP significantly increased the expression of Bax and cleaved caspase-3, and decreased the expression of Bcl-2. In addition, the excellent biosafety of the double-locked nanoparticle was verified. This study provides evidence that ICG-ODA@rNP, with the double lock characteristic and biosafety, which exhibits a targeting effect on RFCA-induced cardiac injury areas, which further reduce electrical conduction recovery in RFCA areas by collaborativing PDT.

Published in International Journal of Pharmaceutics: X

ISSN: 2590-1567 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Medicine: Pharmacy and materia medica
Website: https://www.journals.elsevier.com/international-journal-of-pharmaceutics-x

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