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

doi:10.6023/cjoc202403055

Chinese Journal of Organic Chemistry ›› 2024, Vol. 44 ›› Issue (8): 2530-2537.DOI: 10.6023/cjoc202403055 Previous Articles Next Articles

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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

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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Abstract

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

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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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Fig. & Tab. 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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