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用于研究光动力疗法应用的大型动物模型。

Large animal models for investigating the applications of photodynamic therapy.

作者信息

Zhou Heng-Zong, Wang Dong-Xu, Qian Yu-Qiang, Wei Jia-Qi, Ma Sen, Feng Yu-Jing, Hao Yang

机构信息

Department of Laboratory Animals, College of Animal Sciences, Jilin University, Changchun, Jilin 130062, China.

Zhichuang Gene Editing Animal Model Research Center, Wenzhou Institute of Technology, Wenzhou, Zhejiang 325000, China.

出版信息

Zool Res. 2025 May 18;46(3):551-575. doi: 10.24272/j.issn.2095-8137.2024.445.

DOI:10.24272/j.issn.2095-8137.2024.445
PMID:40259735
Abstract

Photodynamic therapy (PDT) is an emerging minimally invasive therapeutic modality that relies on the activation of a photosensitizing agent by light of a specific wavelength in the presence of molecular oxygen, leading to the generation of reactive oxygen species (ROS). This mechanism facilitates selective cytotoxic effects within pathological tissues and has demonstrated therapeutic potential across diverse disease contexts. However, the broader clinical applications remain limited by photosensitizer selectivity, shallow light penetration, and the risk of off-target cytotoxicity. Recent advancements in PDT have focused on the development of next-generation photosensitizers, the integration of nanotechnology for enhanced delivery and targeting, and the strategic combination of PDT with complementary therapeutic approaches. Experimental animal models play a crucial role in validating the efficacy and safety of PDT, optimizing its therapeutic parameters, and determining its mechanisms of action. This review provides a comprehensive overview of PDT applications in various disease models, including oncological, infectious, and nonconventional indications. Special emphasis is placed on the importance of large animal models in PDT research, such as rabbits, pigs, dogs, and non-human primates, which provide experimental platforms that more closely resemble human physiological and pathological states. The use of these models for understanding the mechanisms of PDT, optimizing therapeutic regimens, and evaluating clinical outcomes is also discussed. This review aims to inform future directions in PDT research and emphasizes the importance of selecting appropriate preclinical animal models to facilitate successful clinical translation.

摘要

光动力疗法(PDT)是一种新兴的微创治疗方式,它依赖于在分子氧存在的情况下,特定波长的光激活光敏剂,从而产生活性氧(ROS)。这种机制有助于在病理组织内产生选择性细胞毒性作用,并已在多种疾病背景下显示出治疗潜力。然而,其更广泛的临床应用仍受到光敏剂选择性、光穿透浅以及脱靶细胞毒性风险的限制。光动力疗法的最新进展集中在开发下一代光敏剂、整合纳米技术以增强递送和靶向性,以及将光动力疗法与互补治疗方法进行策略性结合。实验动物模型在验证光动力疗法的疗效和安全性、优化其治疗参数以及确定其作用机制方面发挥着关键作用。本综述全面概述了光动力疗法在各种疾病模型中的应用,包括肿瘤学、感染性和非常规适应症。特别强调了大型动物模型在光动力疗法研究中的重要性,如兔子、猪、狗和非人灵长类动物,它们提供了更接近人类生理和病理状态的实验平台。还讨论了使用这些模型来理解光动力疗法的机制、优化治疗方案以及评估临床结果。本综述旨在为光动力疗法研究的未来方向提供信息,并强调选择合适的临床前动物模型以促进成功临床转化的重要性。

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本文引用的文献

1
Near-infrared BODIPY photosensitizers for two-photon excited singlet oxygen generation and tumor cell photodynamic therapy.近红外 BODIPY 光敏剂用于双光子激发单线态氧的生成和肿瘤细胞光动力治疗。
Org Biomol Chem. 2024 Jul 10;22(27):5569-5577. doi: 10.1039/d4ob00706a.
2
Heavy-atom-free BODIPY dendrimer: utilizing the spin-vibronic coupling mechanism for two-photon photodynamic therapy in zebrafish.无重原子 BODIPY 树状大分子:利用自旋-振动耦合机制在斑马鱼中进行双光子光动力疗法。
J Mater Chem B. 2024 Jun 27;12(25):6175-6189. doi: 10.1039/d4tb00535j.
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Doble synergetic anticancer activity through a combined chemo-photodynamic therapy and bioimaging of a novel Cas-ZnONPs all-in-one system.
通过新型 Cas-ZnONPs 一体化系统的联合化疗-光动力治疗和生物成像实现双重协同抗癌活性。
J Inorg Biochem. 2024 Sep;258:112623. doi: 10.1016/j.jinorgbio.2024.112623. Epub 2024 May 28.
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Janus liposozyme for the modulation of redox and immune homeostasis in infected diabetic wounds.Janus 脂酶通过调节氧化还原和免疫内稳态来改善感染性糖尿病创面。
Nat Nanotechnol. 2024 Aug;19(8):1178-1189. doi: 10.1038/s41565-024-01660-y. Epub 2024 May 13.
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Investigation into safflower injection as a prophylactic treatment for retinal vein occlusion in a rabbit model.红花注射液防治兔视网膜静脉阻塞的实验研究。
Sci Rep. 2024 Apr 5;14(1):8048. doi: 10.1038/s41598-024-58734-z.
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Repeated photodynamic therapy using a chlorin e6-embedded device to prolong the therapeutic effects on obesity.使用嵌入二氢卟吩e6的装置进行重复光动力疗法以延长对肥胖症的治疗效果。
Obesity (Silver Spring). 2024 May;32(5):911-922. doi: 10.1002/oby.23958. Epub 2024 Apr 1.
7
Globus Lucidus: A porcine study of an intracranial implant designed to deliver closed, repetitive photodynamic and photochemical therapy in glioblastoma.明亮球体:一项关于颅内植入物的猪研究,该植入物旨在对胶质母细胞瘤进行封闭式重复光动力和光化学治疗。
Photodiagnosis Photodyn Ther. 2024 Apr;46:104059. doi: 10.1016/j.pdpdt.2024.104059. Epub 2024 Mar 27.
8
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Anal Chem. 2024 Apr 9;96(14):5615-5624. doi: 10.1021/acs.analchem.4c00227. Epub 2024 Mar 27.
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Water-soluble red fluorescent protein dimers for hypoxic two-photon photodynamic therapy.水溶性红色荧光蛋白二聚体用于缺氧双光子光动力治疗。
J Mater Chem B. 2024 Feb 28;12(9):2413-2424. doi: 10.1039/d3tb02621c.
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Evaluation of Verteporfin as a Novel Antifibrotic Agent in a Rabbit Model of Glaucoma Filtration Surgery: A Pilot Study.维替泊芬作为青光眼滤过手术兔模型新型抗纤维化药物的评估:一项初步研究。
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