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2026 26040099

DOI: https://doi.org/10.6023/A26040099

研究论文

混合卤代亚酞菁的设计合成及其溶酶体靶向光动力治疗研究

  • 张恩泽 ,
  • 田济华 ,
  • 沈一诺 ,
  • 曾绍红 ,
  • 王叶梅 ,
  • 郑芬芬
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  • 江苏科技大学环境与化学工程学院 江苏镇江 212003

收稿日期: 2026-07-10

  网络出版日期: 2026-08-19

基金资助

江苏省基础研究计划资助(BK20251920).

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Design and Synthesis of Mixed Halogenated Subphthalocyanines for Lysosome-Targeted Photodynamic Therapy

  • Zhang Enze ,
  • Tian Jihua ,
  • Shen Yinuo ,
  • Zeng Shaohong ,
  • Wang Yemei ,
  • Zheng Fenfen
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  • School of Environmental and Chemical Engineering, Jiangsu University of Science and Technology, Zhenjiang, Jiangsu 212003

Received date: 2026-07-10

  Online published: 2026-08-19

Supported by

Basic Research Program of Jiangsu province (BK20251920).

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摘要

光动力疗法（PDT）是前景广阔的肿瘤靶向治疗技术,开发高性能光敏染料是其发展的核心关键。亚酞菁（SubPc）作为性能优异的大环光敏染料,在肿瘤PDT治疗中极具应用价值。本研究通过一锅法制备四种氟氯梯度取代低对称亚酞菁（SubPc 4-7）,结合理论计算系统探究卤素取代对其光物理及抗肿瘤性能的调控规律。结果表明,随氯取代比例升高,分子吸收与荧光波长持续红移;荧光量子产率与单线态氧产率呈负相关,多氯累加重原子效应可有效促进系间窜越,提升光敏能力。该系列分子具有良好水相光学稳定性,可靶向肿瘤细胞溶酶体并产生活性氧。体外实验证实SubPc 4肿瘤细胞杀伤率达82%,小鼠模型及组织切片实验进一步验证其优异的体内PDT抑瘤效果。本研究为亚酞菁靶向光动力抗肿瘤应用提供了重要实验依据。

关键词： 光动力疗法; 亚酞菁; 卤素取代; 单线态氧; 溶酶体靶向

本文引用格式

张恩泽 , 田济华 , 沈一诺 , 曾绍红 , 王叶梅 , 郑芬芬 . 混合卤代亚酞菁的设计合成及其溶酶体靶向光动力治疗研究[J]. 化学学报, 2026 : 26040099 . DOI: 10.6023/A26040099

Abstract

Photodynamic therapy (PDT) is a promising targeted tumor treatment strategy, and developing high-performance photosensitizers is crucial for its advancement. As excellent macrocyclic photosensitive dyes, subphthalocyanines (SubPcs) show great application potential in tumor PDT. In this study, four low-symmetry SubPc derivatives with gradient fluoro-chloro substitution (SubPc 4-7) were prepared via a one-pot method. Combined with theoretical calculations, the regulatory effects of halogen substitution on their photophysical and antitumor properties were systematically investigated. The results showed that increasing chlorine substitution ratio led to progressive redshifts in both absorption and fluorescence emission wavelengths. Fluorescence quantum yield was negatively correlated with singlet oxygen quantum yield, and the cumulative heavy-atom effect of multiple chlorine atoms effectively promoted intersystem crossing, thereby enhancing photosensitization capability. These derivatives exhibited good optical stability in aqueous environments and could target lysosomes of tumor cells to generate reactive oxygen species. In vitro experiments confirmed that SubPc 4 achieved a tumor cell killing rate of 82%. In vivo mouse models and tissue section analysis further verified its potent antitumor efficacy in PDT. This study provides an important experimental basis for the application of SubPc derivatives in targeted photodynamic antitumor therapy.

Key words： Photodynamic Therapy; Subphthalocyanine; Halogen substitution; Singlet oxygen; Lysosome targeting

参考文献

[1] Cramer G. M.; Cengel K. A.; Busch, T. M. Cancer Res.2022, 82, 534.
[2] Cai Y.-Y.; Chai T.; Nguyen W.; Liu J.-Y.; Xiao E.-H.; Ran X.; Ran Y. -P.; Du D.; Chen W.; Chen, X.-Y. Sig. Transduct. Target. Ther.2025, 10, 115.
[3] Raab O.Z. Biol. 1900, 39, 524.
[4] Lipson R. L.; Baldes, E. J. Arch. Dermatol.1960, 82, 508.
[5] Mei J.; Hong Y.-N.; Lam J. W. Y.; Qin A.-J.; Tang Y.-H.; Tang B.-Z. Adv. Mater.2014, 26, 5429.
[6] Yu Q.-S.; Qi C.; Gu S.-X.; Yang X.-D.; Jiang Q.; Wei R.-B.; Shi P.-F.Acta. Chim. Sinica. 2025, 83, 579. (in Chinese)
(于千水, 戚聪, 顾顺心, 杨欣达, 姜琴, 魏荣斌, 施鹏飞化学学报 2025, 83, 579.)
[7] Li J.-Q.; Huang Y.-Q.; Ding G.-D.; Zhang R.; Liu X.-F.; Fan Q.-L.; Huang W. Acta. Chim. Sinica. 2025, 83, 1324. (in Chinese)
(李佳启, 黄艳琴, 丁桂第, 张瑞, 刘兴奋, 范曲立, 黄维化学学报 2025, 83, 1324.)
[8] Zhang Y.-Q.; Zhan C.; Gong Y.; Lu F.; Fan, Q.-L. Acta. Chim. Sinica. 2024, 82, 1226. (in Chinese)
(张雨琦, 占辰, 贡祎, 陆峰, 范曲立化学学报 2024, 82, 1226.)
[9] Huang Y.-Q.; Luo J.-W.; Li J.-Q.; Zhang R.; Liu X.-F.; Fan Q.-L.; Huang W. Acta. Chim. Sinica. 2024, 82, 1. (in Chinese)
(黄艳琴, 罗集文, 李佳启, 张瑞, 刘兴奋, 范曲立, 黄维化学学报 2024, 82, 1.)
[10] Li Y.; Wang W.; Zhang Y.-T.; Xiao S.-Z.; Lan H.-C.; Geng, P. Acta. Chim. Sinica.2024, 82, 443.(in Chinese)
(李燕,王玮, 张毓婷, 肖述章,兰海闯,耿鹏化学学报2024, 82, 443.)
[11] Zhang S.-H.; Yang N.-L.; Zhao H.-T.; Sun S.-M.; Chen P.-D.; Cheng C.-W.; Wang C.-J.; He W.-W.; Zhang L.-F.; Cheng L.;Cheng, Z.-P. Adv. Funct. Mater.2026, 36, e13920.
[12] Ritz J. M.; Khakimzhan A.; Dalluge J. J.; Noireaux V.; Puchner, E. M. J. Am. Chem. Soc.2025, 147, 7588.
[13] Niu P.-Y.; Dai J.-L.; Wang Z.-Y.; Wang Y.-Y.; Feng D.-X.; Li Y.-Y.; Miao W.-J. Pharmaceuticals2022, 15, 156.
[14] Wang L.-C.; Mei A.-Q.; Li N.; Ruan X.-H.; Sun X.; Cai Y.; Shao J.-J.; Dong, X.-C. Chinese Chem. Lett.2024, 35, 108974.
[15] Labella J.; Torres T. Trends Chem.2023, 5, 353.
[16] Lavarda G.; Labella J.; Martínez-Díaz M. V.; Rodríguez-Morgade M. S.; Osuka A.; Torres, T. Chem. Soc. Rev.2022, 51, 9482.
[17] Demuth J.; Gallego L.; Kozlikova M.; Machacek M.; Kucera R.; Torres T.; Martinez-Diaz M. V.; Novakova, V. J. Med. Chem.2021, 64, 17436.
[18] Garcia-Calvo J.; Chen X.-X.; Sakai N.; Matile S.; Torres, T. Phys. Chem. Chem. Phys.2024, 26, 4759.
[19] Casellas N. M.; Dai G.-L.; Xue E. Y.; Fonseca A.; Ng D. K. P.; Garcia-Iglesias M.; Torres T. Chem. Commun.2022, 58, 669.
[20] Bodedla G. B.; Ke S.-Y.; Cao Y.-B.; Zhang L.-J.; Wong, W.-Y. J. Mater. Chem. C,2026, 14, 119.
[21] Gotfredsen H.; Thiel D.; Greissel P. M.; Chen L.; Krug M.; Papadopoulos I.; Ferguson M. J.; Nielsen M. B.; Torres T.; Clark T.; Guldi D. M.; Tykwinski, R. R., J. Am. Chem. Soc.2023, 145, 9548.
[22] Chan J. Y. M.; Kawata T.; Kobayashi N.; Ng, D. K. P. Angew. Chem. Int. Ed.2019, 58, 2272.
[23] Skvortsov I. A.; Nikitin I. A.; Lazovskiy D. A.; Stuzhin, P. A. Dyes Pigm.2022, 202, 110282.
[24] Skvortsov I. A.; Chufarin A. E.; Zaitsev M. V.; Kirakosyan G. A.; Stuzhin, P. A. Asian J. Org. Chem.2023, 12, e202300425.
[25] Kovkova U. P.; Skvortsov I. A.; Khodov I. A.; Efimov S. V.; Zhabanov Y. A.; Somov N. V.; Liang X.; Pakhomov G. L.; Stuzhin, P. A. J. Porphyrins Phthalocyanines2023, 27, 600.
[26] Zhou, S.-T; Lv, X.-J; Li, M.-H; Gao, Z.-J; Tu, S.-N; Qiao, S.-S; Mo, M.-J; Tang, X.; Wang, Y.-M; Sun, S.-S. Molecules2023, 28,725.
[27] Labella J.; Momblona C.; Klipfel N.; Kanda H.; Kinge S.; Nazeeruddin M. K.; Torres T.J. Mater. Chem. C 2021, 9, 16298.
[28] Tejerina L.; Labella J.; Martínez-Fernández, L.; Corral, I.; Martínez-Díaz, M. V.; Torres, T.Chem. Eur. J. 2021, 27, e202101991.
[29] Tejerina L.;Martinez-Diaz, M. V.; Torres, T.Org. Lett. 2019, 21, 3275.
[30] Skvortsov I. A.; Nikitin I. A.; Lazovskiy D. A.; Stuzhin P. A.Dyes Pigm. 2022, 202, 110282.
[31] Kovkova U. P.; Skvortsov I. A.; Khodov I. A.; Efimov S. V.; Zhabanov Y. A.; Somov N. V.; Liang X.; Pakhomov G. L.; Stuzhin P. A.J. Porphyrins Phthalocyanines 2023, 27, 600.
[32] Arabei S. M.; Pershukevich P. P.; Belkov M. V.; Gladkov L. L.; Tabolich A. A.; Solovyov K. N.; Skvortsov I. A.; Stuzhin P. A.Spectrochim. Acta A 2023, 303, 123254.
[33] Necedova M.; Magdolen P.; Fülöpova A.; Cigan M.; Zahradník P.; Filo J.Dyes Pigm. 2016, 130, 24-36.
[34] Lavarda G.; Labella J.; Martinez-Diaz, M. V.; Rodriguez-Morgade, M. S.; Osuka, A.; Torres, T.Chem. Soc. Rev. 2022, 51, 9482-9619.
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