利用光诱导电子转移机制构筑I型聚集诱导发光光敏剂用于光动力治疗

doi:10.6023/cjoc202403055

有机化学 ›› 2024, Vol. 44 ›› Issue (8): 2530-2537.DOI: 10.6023/cjoc202403055 上一篇下一篇

研究论文

利用光诱导电子转移机制构筑I型聚集诱导发光光敏剂用于光动力治疗

贾涵羽^a, 俞岳文^a, 冯光雪^a^,^*(), 唐本忠^b

a 华南理工大学材料科学与工程学院发光材料与器件国家重点实验室广东省分子聚集发光重点实验室广州 510640
b 香港中文大学(深圳)理工学院深圳分子聚集体科学与工程研究院广东深圳 518172

收稿日期:2024-03-31 修回日期:2024-05-29 发布日期:2024-06-13
作者简介:
† 共同第一作者.
基金资助:
广州市应用基础研究计划项目(2024A04J2466); 国家自然科学基金委青年科学基金(22205067); 广东省分子聚集发光重点实验室(2023B1212060003)

Construction of Type I Aggregation-Induced Emission Photosensitizers for Photodynamic Therapy via Photoinduced Electron Transfer Mechanism

Hanyu Jia^a, Yuewen Yu^a, Guangxue Feng^a(), BenZhong Tang^b

a Guangdong Provincial Key Laboratory of Luminescence from Molecular Aggregates, State Key Laboratory of Luminescent Materials and Devices, School of Materials Science and Engineering, South China University of Technology, Guangzhou 510640
b Shenzhen Institute of Aggregate Science and Technology, School of Science and Engineering, The Chinese University of Hong Kong, Shenzhen, Guangdong 518172

Received:2024-03-31 Revised:2024-05-29 Published:2024-06-13
Contact: *E-mail: fenggx@scut.edu.cn
About author:
† These authors contributed equally to this work.
Supported by:
Guangzhou Municipal Science and Technology Bureau(2024A04J2466); National Natural Science Foundation of China(22205067); Guangdong Provincial Key Laboratory of Luminescence from Molecular Aggregates(2023B1212060003)

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摘要/Abstract

光动力治疗(PDT)作为一种非侵入性抗癌方式, 凭借其低毒、高时空选择性及操作简捷可控等优势受到越来越多的关注. 光动力治疗主要依靠光敏剂在特定激发波长光源照射下产生活性氧(ROS)以消融癌细胞. 然而, 乏氧是实体肿瘤的固有属性, 而传统的II型光敏剂对氧气依赖度高, 制约着PDT的治疗效果. 因此, 设计开发对氧气依赖度低的I型光敏剂用于抗肿瘤具有重要研究意义. 报道了一种通过引入光诱导电子转移(PET)机制制备高效I型光敏剂的设计策略. 通过在具有聚集诱导发光(AIE)活性的(Z)-2-(5-(4-(二乙氨基)-2-羟基亚苄基)-4-氧代-3-苯基噻唑烷-2-亚基)丙二腈(DR-OH)上引入4-硝基苄基, 得到光敏剂DR-NO₂, 光激发后会发生PET过程, 使得DR-NO₂的荧光得到一定程度的淬灭, 促进三线态产生, 同时还促进分子内电荷分离和更有效的分子内电子转移, 进而促进其I型ROS尤其是超氧自由基的产生. 此外, 通过纳米工程制备得到DR-NO₂纳米粒子具有较小的纳米尺寸、优秀的肿瘤细胞摄取能力以及进一步增强的I型ROS产生能力, 在光照下对MCF-7细胞展现出优秀的PDT杀伤能力. 这种PET策略开发的I型ROS的光敏剂在抗乏氧肿瘤PDT应用中具有巨大潜力.

关键词: 光动力治疗, 聚集诱导发光, 光致电子转移, I型光敏剂, 乏氧肿瘤

Photodynamic therapy (PDT) as a non-invasive anticancer modality has received increasing attention due to its advantages of noninvasiveness, high temporospatial selectivity, simple and controllable operation, etc. PDT mainly relies on the generation of toxic reactive oxygen species (ROS) by photosensitizers (PSs) under the light irradiation to cause cancer cell apoptosis and death. However, solid tumors usually exhibit an inherent hypoxic microenvironment, which greatly limits the PDT efficacy of these high oxygen-dependent conventional type II PSs. Therefore, it is of great importance to design and develop efficient type I PSs that are less oxygen-dependent for the treatment of hypoxic tumors. Herein, a new strategy for the preparation of efficient type I PSs by introducing the photoinduced electron transfer (PET) mechanism is reported. DR-NO₂ is obtained by introducing 4-nitrobenzyl to (Z)-2-(5-(4-(diethylamino)-2-hydroxybenzylidene)-4-oxo-3-phenylthiazolidin-2- ylidene)malononitrile (DR-OH) with aggregation-induced emission (AIE) feature. The AIE feature ensures their high ROS generation efficiency in aggregate, and the PET process leads to fluorescence quenching of DR-NO₂ to promote triplet state formation, which also promotes intramolecular charge separation and electron transfer that is conducive for type I ROS particularly superoxide radicals generation. In addition, DR-NO₂ nanoparticles are prepared by nanoprecipitation to possess nanoscaled sizes, high cancer cell uptake, and excellent type I ROS generation ability, which results in an excellent performance in PDT ablation of MCF-7 cancer cells. This PET strategy for the development of type I PSs possesses great potential for PDT applications against hypoxic tumors.

Key words: photodynamic therapy, aggregation-induced emission, photoinduced electron transfer, type I photosensitizer, hypoxic tumor microenvironment

引用此文

贾涵羽, 俞岳文, 冯光雪, 唐本忠. 利用光诱导电子转移机制构筑I型聚集诱导发光光敏剂用于光动力治疗[J]. 有机化学, 2024, 44(8): 2530-2537.

Hanyu Jia, Yuewen Yu, Guangxue Feng, BenZhong Tang. Construction of Type I Aggregation-Induced Emission Photosensitizers for Photodynamic Therapy via Photoinduced Electron Transfer Mechanism[J]. Chinese Journal of Organic Chemistry, 2024, 44(8): 2530-2537.

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图/表 7

Scheme 1. Schematic illustration of PET-enhanced Type I ROS generation

Scheme 2. Synthetic route of DR-OH and DR-NO2

Figure 1. (A) Absorption and (B) PL spectra of DR-OH and DR-NO2 in DCM, (C) PL spectra of DR-NO2 (10 μmol/L) and (D) plot of relative PL intensity (I/I0) vs water fraction (fw, φ) in the mixture of THF/water (I0 is the PL intensity in pure THF solution, and I is the PL intensity in the mixture), and PL spectra of (E) DR-OH and (F) DR-NO2 in different solvents with various polarities ([AIE PSs]=10 μmol/L)

Figure 2. Time-course plots of (A) DCFH fluorescence enhancement and (B) ABDA fluorescence decomposition, (C) DHR123 and (D) HPF fluorescence enhancement in the presence of different PSs under light irradiation (20 mW?cm－2), (E) summary of different ROS generation ability for DR-OH and DR-NO2 upon 10 min of white light irradiation ([AIE PSs]=10 μmol/L, [DCFH]=50 μmol/L, [ABDA]=50 μmol/L, [DHR123]=20 μmol/L, [HPF]=10 μmol/L), and (F) schematic illustration of intramolecular PET (the frontier molecular orbital distributions of DR-OH and 4-nitrotoluene at the optimized ground state geometry)

Figure 3. (A) Particle size distributions and TEM images of DR-NO2 NPs (scale bar: 200 nm), (B) absorption and emission spectra of DR-NO2 NPs, and time-course plots of (C) DCFH, (D) DHR123 fluorescence enhancement in the presence of Ce6 and DR-NO2 NPs under light irradiation (20 mW?cm－2)

Figure 4. (A) CLSM images of MCF-7 cells incubated with DR-NO2 NPs for different times and (B) intracellular ROS evaluation with DR-NO2 NPs treated MCF-7 cells ([AIE PSs]=50 μg/mL, [DCFH-DA]=50 μmol/L, scale bar: 20 μm)

Figure 5. (A) Viabilities of DR-NO2 NPs treated MCF-7 cells with or without light irradiation (100 mW?cm－2, 30 min) and (B) live/dead staining of DR-NO2 NPs treated MCF-7 cancer cells with or without light irradiation ([Calcein-AM]=1 μmol/L, [PI]=1 mg?mL－1, scale bar: 50 μm)

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利用光诱导电子转移机制构筑I型聚集诱导发光光敏剂用于光动力治疗

Construction of Type I Aggregation-Induced Emission Photosensitizers for Photodynamic Therapy via Photoinduced Electron Transfer Mechanism

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