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·1880· 精细化工 FINE CHEMICALS 第 38 卷

还原平衡被破坏。结果表明，因化合物Ⅳ使细胞内 剂的合成提供了新的思路。此外，GSH 耗竭引起活
NO 水平提升，从而消耗部分 GSH，使细胞内 ROS 性氧成分浓度提高是铁死亡的重要特征之一，尚需进
水平增加。这些结果也与化合物Ⅳ光毒性增强有关。 一步进行结构优化以及与铁死亡机制关联性的研究。

参考文献：
[1] ALLISON R R, KEYVAN M. Photodynamic therapy (PDT): PDT
mechanisms[J]. Clinical Endoscopy, 2013, 46(1): 24-29.
[2] JUZENIENE A, MOAN J. The history of PDT in norway: Part one:
Intification of basic mechanisms of general PDT[J]. Photodiagnosis
& Photodynamic Therapy, 2007, 4(1): 3-11.
[3] CASTANO A P, DEMIDOVA T N, HAMBLIN M R. Mechanisms
in photodynamic therapy: Part one—Photosensitizers, photochemistry
and cellular localization[J]. Photodiagnosis & Photodynamic Therapy,
2004, 1(4): 279-293.
[4] ROBERTSON C A, EVANS D H, ABRAHAMSE H. Photodynamic
therapy (PDT): A short review on cellular mechanisms and cancer
research applications for PDT[J]. Journal of Photochem and
Photobiol B, 2009, 96(1): 1-8.
[5] GOLD M H. History of photodynamic therapy[M]. New York:
Hotodynamic Therapy in Dermatology(Springer), 2011.
[6] BOYLE L, KAUFMANN W E. The behavioral phenotype of FMR1
mutations[J]. American Journal of Medical Genetics, 2010, 154(4):
469-476.
[7] GOMER C J. Preclinical examination of first and second generation
photosensitizers used in photodynamic therapy[J]. Photochemistry &
Photobiology, 1991, 54(6): 1093-1107.
[8] WU B (吴彬)，LU J Z (陆家政)，HE L M (贺丽敏). Research
progress and clinical application of second-generation
photosensitizers[J]. Academic Journal of Guangdong College of
Pharmacy(广东药学院学报), 2008, 24(5): 527-531.
[9] ROVERS J P, SAARNAK A E, MOLINA A, et al. Effective
treatment of liver metastases with photodynamic therapy, using the
second-generation photosensitizer meta-tetra(hydroxyphenyl)chlorin
(mTHPC), in a rat model[J]. British Journal of Cancer, 1999, 81(4):
600-608.
[10] SCHUIMAKER J J, VOGEL E W, NAGELKERKE J F, et al.
Mutagenicity and dark toxicity of the second-generation
photosensitizer bacteriochlorin a[J]. Journal of Photochemistry &
Photobiology B：Biology, 1998, 47(2/3): 211-215.
®
[11] SENGE M O, BRANDT J C. Temoporfin (Foscan , 5, 10, 15,
20-tetra(m-hydroxyphenyl)chlorin) — A second-generation
图 4 细胞内 NO（a）、ROS（b）和 GSH/GSSG 水平（c） photosensitizer[J]. Photochemistry & Photobiology, 2011, 87(6):
Fig. 4 Intracellular NO (a), ROS (b) and GSH/GSSG level (c) 1240-1296.
[12] NOWAK S A, PERGOL P, PADZIK G A. Photodynamic method of
cancer diagnosis and therapy-mechanisms and applications[J].
3 结论 Postepy Biochem, 2013, 59(1): 53-63.
[13] ZHANG Y, NG D K P, FONG W P. Antitumor immunity induced by
本文基于二氢卟吩 e6 骨架，设计并合成一种含 the photodynamic action of BAM-SiPc, a silicon (Ⅳ) phthalocyanine
photosensitizer[J]. Cellular & Molecular Immunology, 2019, 16(7):
有呋咱的 NO 供体类光敏剂。在溶液中，化合物Ⅳ 676-678.
具有与二氢卟吩 e6 相似的光物理及光化学性能。相 [14] BALIK E P, ETIN M, GKSEL M, et al. Improved targeting for
photodynamic therapy via a biotin–phthalocyanine conjugate:
比于母体化合物二氢卟吩 e6，由于呋咱基团的引入， Synthesis, photophysical and photochemical measurements, and in
化合物Ⅳ的细胞摄取率提高了 33 倍，在浓度为 vitro cytotoxicity assay[J]. New Journal of Chemistry, 2020, 8(44):
3392-3401.
33 μmol/L 时，细胞存活率低于 4%，抗肿瘤活性明
[15] JOSEFSEN L B, BOYLE R W. Photodynamic therapy: Novel
显增强。在 PDT 过程中，化合物Ⅳ可通过增加 Hela third-generation photosensitizers one step closer[J]. British Journal of
细胞内 NO 浓度、降低 GSH 水平诱导细胞内 ROS Pharmacology, 2008, 154(1): 1-3.
[16] CHEN Z L (陈祖林). Progress in the study of synergistic effect of
显著增加，影响细胞内的氧化还原平衡，产生氧化 photodynamic therapy on tumor[J]. Laser Journal(激光杂志), 2015,
应激，提高抑制肿瘤细胞增殖的活性。综上所述， 36(5): 8-10.
[17] STAR W M. Light dosimetry in vivo[J]. Physics in Medicine &
含有呋咱的二氢卟吩 e6 缀合物有潜力应用于肿瘤
Biology, 1997, 42(5): 763-787.
的 PDT，本研究也为新型、高效的光敏抗肿瘤治疗 （下转第 1895 页）