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基于非菁染料构建的P-IR890纳米光敏剂实现的深部近红外光激发稳定协同光动力与光热疗法

Deep near infrared light-excited stable synergistic photodynamic and photothermal therapies based on P-IR890 nano-photosensitizer constructed a non-cyanine dye.

作者信息

Jiang Dawei, Chen Chao, Dai Peng, Li Caiyan, Feng Zhiyi, Dong Na, Wu Fenzan, Xu Junpeng, Wu Ping, Chu Liuxi, Li Shengcun, Li Xiaokun, Yang Youjun, Zhang Weian, Wang Zhouguang

机构信息

Affiliated Cixi Hospital, Wenzhou Medical University, Ningbo 325300, China.

Shanghai Key Laboratory of Functional Materials Chemistry, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai 200237, China.

出版信息

Asian J Pharm Sci. 2024 Oct;19(5):100955. doi: 10.1016/j.ajps.2024.100955. Epub 2024 Aug 24.

Abstract

The cyanine dyes represented by IR780 can achieve synergistic photodynamic therapy (PDT) and photothermal therapy (PTT) under the stimulation of near-infrared (NIR) light (commonly 808 nm). Unfortunately, the stability of NIR-excited cyanine dyes is not satisfactory. These cyanine dyes can be attacked by self-generated reactive oxygen species (ROS) during PDT processes, resulting in structural damage and rapid degradation, which is fatal for phototherapy. To address this issue, a novel non-cyanine dye (IR890) was elaborately designed and synthesized by our team. The maximum absorption wavelength of IR890 was located in the deep NIR region ( 890 nm), which was beneficial for further improving tissue penetration depth. Importantly, IR890 exhibited good stability when continuously illuminated by deep NIR light. To improve the hydrophilicity and biocompatibility, the hydrophobic IR890 dye was grafted onto the side chain of hydrophilic polymer (POEGMA-b-PGMA-g-C[bond, triple bond]CH) click chemistry. Then, the synthesized POEGMA--PGMA--IR890 amphiphilic polymer was utilized to prepare P-IR890 nano-photosensitizer self-assembly method. Under irradiation with deep NIR light (850 nm, 0.5 W/cm, 10 min), the dye degradation rate of P-IR890 was less than 5%. However, IR780 was almost completely degraded with the same light output power density and irradiation duration. In addition, P-IR890 could stably generate a large number of ROS and heat at the same time. It was rarely reported that the stable synergistic combination therapy of PDT and PTT could be efficiently performed by a single photosensitizer irradiation with deep NIR light. P-IR890 exhibited favorable anti-tumor outcomes through apoptosis pathway. Therefore, the P-IR890 could provide a new insight into the design of photosensitizers and new opportunities for synergistic combination therapy of PDT and PTT.

摘要

以IR780为代表的花菁染料在近红外(NIR)光(通常为808 nm)刺激下可实现协同光动力疗法(PDT)和光热疗法(PTT)。不幸的是,近红外激发的花菁染料稳定性并不理想。这些花菁染料在光动力疗法过程中会受到自身产生的活性氧(ROS)攻击,导致结构破坏和快速降解,这对光疗来说是致命的。为解决这一问题,我们团队精心设计并合成了一种新型非花菁染料(IR890)。IR890的最大吸收波长位于近红外深区(890 nm),这有利于进一步提高组织穿透深度。重要的是,当用近红外深光持续照射时,IR890表现出良好的稳定性。为提高亲水性和生物相容性,通过点击化学将疏水性的IR890染料接枝到亲水性聚合物(POEGMA-b-PGMA-g-C≡CH)的侧链上。然后,利用合成的POEGMA-b-PGMA-IR890两亲聚合物通过自组装方法制备P-IR890纳米光敏剂。在近红外深光(850 nm,0.5 W/cm²,10分钟)照射下,P-IR890的染料降解率小于5%。然而,在相同的光输出功率密度和照射持续时间下,IR780几乎完全降解。此外,P-IR890可同时稳定地产生大量ROS和热量。很少有报道称,通过单一光敏剂在近红外深光照射下能高效地实现稳定的光动力疗法和光热疗法协同联合治疗。P-IR890通过凋亡途径展现出良好抗肿瘤效果。因此,P-IR890可为光敏剂设计提供新见解,并为光动力疗法和光热疗法协同联合治疗带来新机遇。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac4d/11525468/b13c6beb8317/ga1.jpg

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