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Progress in Chemistry 2021, Vol. 33 Issue (9): 1473-1481 DOI: 10.7536/PC200878 Previous Articles   Next Articles

• Review •

Photodynamic Therapy of Hypoxic Tumors with Ir(Ⅲ) Complexes

Zilin Zhu, Zhongxian Fan, Mengzhao Miao, Huaiyi Huang()   

  1. School of Pharmaceutical Science (Shenzhen), Sun Yat-sen University, Guangzhou 510275, China
  • Received: Revised: Online: Published:
  • Contact: Huaiyi Huang
  • Supported by:
    National Natural Science Foundation of China(NSFC22007104); Guangdong Natural Science Foundation(2019A1515110601); Guangdong Natural Science Foundation(2021B1515020050); Science, Technology and Innovation Commission of Shenzhen Municipality Project(JCYJ20190807152616996)
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Photodynamic therapy has become a new method to treat cancer because of noninvasive, controllable features and less drug resistance compared with chemotherapy. The photo-sensitization pathway involves the photoactivation of molecular oxygen by photosensitizer. However, due to the hypoxic environment of solid tumors, the photodynamic therapeutic effect of traditional photosensitizers is severely suppressed. Metallic Ir(Ⅲ) complexes exhibit excellent photo-physical and photo-chemical properties which make them ideal next-generation photosensitizers for photodynamic therapy. It has been reported that some novel Ir(Ⅲ) complexes show excellent photodynamic therapy effect towards hypoxic tumors. In this review, we focus on the recent studies on the application of Ir(Ⅲ) complexes to photodynamic therapy under hypoxia. Furthermore, the applications of Ir(Ⅲ) complexes containing nanocomposite system for hypoxic photodynamic therapy are also summarized, with the hope to provide guidance for the development of novel and efficient photosensitizers for hypoxic tumor.

Contents

1 Introduction

2 Photodynamic therapy (PDT) based on iridium complexes

2.1 Type I PDT in the hypoxic environment

2.2 Type II PDT in the hypoxic environment

3 Nanocomposite system for PDT of hypoxic tumors

3.1 Up-conversion nanocomposite system

3.2 Polymer nanocomposite system

4 Conclusion and outlook

Key words: iridium complexes, hypoxia, photodynamic therapy, nanocomposite system
Fig. 1 Chemical structures of complexes 1a~c、2a~c and 3a~c[29]
Fig. 2 Chemical structures of complexes 4a and 4b[30]
Fig. 3 Chemical structures of complexes 5a~d[35,36]
Fig. 4 Chemical structure of complex 6[37]
Fig. 5 Chemical structure of complex 7[38]
Fig. 6 Chemical structures of complexes 8a and 8b[45]
Fig. 7 Chemical structures of complexes 9a~d[46]
Fig. 8 Chemical structures of complexes 10a~d[55]
Fig. 9 Chemical structures of complexes 11[56]
Fig.10 Schematic illustration of the fabrication of UCNP@IrYCF127 and its anticancer pattern[70]. Copyright 2019, American Chemical Society.
Fig. 11 Design strategy of the phosphorescent polymer dots (13/PSMA dots) for hypoxia imaging and the mechanisms of 13/PSMA dots in photodynamic therapy[72]. Copyright 2017, American Chemical Society.
[1]
Moulder J E, Rockwell S. Cancer Metastasis Rev., 1987, 5(4): 313.

doi: 10.1007/BF00055376
[2]
Li Y C, Jeon J, Park J H. Cancer Lett., 2020, 490: 31.

doi: 10.1016/j.canlet.2020.05.032
[3]
Brown J M, Wilson W R. Nat. Rev. Cancer, 2004, 4(6): 437.

doi: 10.1038/nrc1367
[4]
Wilson W R, Hay M P. Nat. Rev. Cancer, 2011, 11(6): 393.

doi: 10.1038/nrc3064
[5]
Bristow R G, Hill R P. Nat. Rev. Cancer, 2008, 8(3): 180.

doi: 10.1038/nrc2344 pmid: 18273037
[6]
Dougherty T J, Gomer C J, Henderson B W, Jori G, Kessel D, Korbelik M, Moan J, Peng Q. J. Natl. Cancer Inst., 1998, 90(12): 889.

pmid: 9637138
[7]
Plaetzer K, Krammer B, Berlanda J, Berr F, Kiesslich T. Lasers Med. Sci., 2009, 24(2): 259.

doi: 10.1007/s10103-008-0539-1
[8]
Yoon I, Li J Z, Shim Y K. Clin. Endosc., 2013, 46(1): 7.

doi: 10.5946/ce.2013.46.1.7 pmid: 23423543
[9]
Gross S, Gilead A, Scherz A, Neeman M, Salomon Y. Nat. Med., 2003, 9(10): 1327.

doi: 10.1038/nm940
[10]
Huang Z, Xu H P, Meyers A D, Musani A I, Wang L W, Tagg R, Barqawi A B, Chen Y K. Technol. Cancer Res. Treat., 2008, 7(4): 309.

doi: 10.1177/153303460800700405
[11]
Foote C S. Science, 1968, 162(3857): 963.

pmid: 4972417
[12]
Bhuvaneswari R, Gan Y Y, Soo K C, Olivo M. Cell. Mol. Life Sci., 2009, 66(14): 2275.

doi: 10.1007/s00018-009-0016-4 pmid: 19333552
[13]
Zheng Y, He L, Zhang D Y, Tan C P, Ji L N, Mao Z W. Dalton Trans., 2017, 46(34): 11395.

doi: 10.1039/c7dt02273e pmid: 28813052
[14]
Tao P, Li W L, Zhang J, Guo S, Zhao Q, Wang H, Wei B, Liu S J, Zhou X H, Yu Q, Xu B S, Huang W. Adv. Funct. Mater., 2016, 26: 881.

doi: 10.1002/adfm.v26.6
[15]
Abrahamse H, Hamblin M R. Biochem. J., 2016, 473(4): 347.

doi: 10.1042/BJ20150942 pmid: 26862179
[16]
Allison R R, Sibata C H. Photodiagnosis Photodyn. Ther., 2010, 7(2): 61.

doi: 10.1016/j.pdpdt.2010.02.001 pmid: 20510301
[17]
Dolmans D E J G J, Fukumura D, Jain R K. Nat. Rev. Cancer, 2003, 3(5): 380.

doi: 10.1038/nrc1071
[18]
Kelly J F, Snell M E. J. Urol., 1976, 115(2): 150.

doi: 10.1016/S0022-5347(17)59108-9
[19]
Mistry P, Kelland L, Abel G, Sidhar S, Harrap K. Br. J. Cancer, 1991, 64(2): 215.

doi: 10.1038/bjc.1991.279
[20]
Holford J, Beale P J, Boxall F E, Sharp S Y, Kelland L R. Eur. J. Cancer, 2000, 36(15): 1984.

pmid: 11000581
[21]
Dai Y L, Yang Z, Cheng S Y, Wang Z L, Zhang R L, Zhu G Z, Wang Z T, Yung B C, Tian R, Jacobson O, Xu C, Ni Q Q, Song J B, Sun X L, Niu G, Chen X Y. Adv. Mater., 2018, 30(8): 1704877.

doi: 10.1002/adma.v30.8
[22]
Dai Y L, Cheng S Y, Wang Z L, Zhang R L, Yang Z, Wang J J, Yung B C, Wang Z T, Jacobson O, Xu C, Ni Q Q, Yu G C, Zhou Z J, Chen X Y. ACS Nano, 2018, 12(1): 455.

doi: 10.1021/acsnano.7b06852
[23]
Ma P G, Xiao H H, Yu C, Liu J H, Cheng Z Y, Song H Q, Zhang X Y, Li C X, Wang J Q, Gu Z, Lin J. Nano Lett., 2017, 17(2): 928.

doi: 10.1021/acs.nanolett.6b04269
[24]
Liou G Y, Storz P. Free. Radic. Res., 2010, 44(5): 479.

doi: 10.3109/10715761003667554
[25]
Bystrom L M, Guzman M L, Rivella S. Antioxid. Redox Signal., 2014, 20(12): 1917.

doi: 10.1089/ars.2012.5014
[26]
Samuel E L G, Marcano D C, Berka V, Bitner B R, Wu G, Potter A, Fabian R H, Pautler R G, Kent T A, Tsai A L, Tour J M. PNAS, 2015, 112(8): 2343.

doi: 10.1073/pnas.1417047112 pmid: 25675492
[27]
Yao J, Cheng Y, Zhou M, Zhao S, Lin S C, Wang X Y, Wu J, Li S R, Wei H. Chem. Sci., 2018, 9(11): 2927.

doi: 10.1039/C7SC05476A
[28]
Shen Z Y, Song J B, Yung B C, Zhou Z J, Wu A G, Chen X Y. Adv. Mater., 2018, 30(12): 1704007.

doi: 10.1002/adma.v30.12
[29]
Novohradsky V, Vigueras G, Pracharova J, Cutillas N, Janiak C, Kostrhunova H, Brabec V, Ruiz J, Kasparkova J. Inorg. Chem. Front., 2019, 6(9): 2500.

doi: 10.1039/c9qi00811j
[30]
Novohradsky V, Rovira A, Hally C, Galindo A, Vigueras G, Gandioso A, Svitelova M, Bresolí-Obach R, Kostrhunova H, Markova L, Kasparkova J, Nonell S, Ruiz J, Brabec V, Marchán V. Angew. Chem. Int. Ed., 2019, 58(19): 6311.

doi: 10.1002/anie.v58.19
[31]
Lv W, Xia H T, Zhang K Y, Chen Z J, Liu S J, Huang W, Zhao Q. Mater. Horiz., 2017, 4(6): 1185.

doi: 10.1039/C7MH00726D
[32]
Lv W, Zhang Z, Zhang K Y, Yang H R, Liu S J, Xu A Q, Guo S, Zhao Q, Huang W. Angew. Chem. Int. Ed., 2016, 55(34): 9947.

doi: 10.1002/anie.201604130
[33]
Nam J S, Kang M G, Kang J, Park S Y, Lee S J C, Kim H T, Seo J K, Kwon O H, Lim M H, Rhee H W, Kwon T H. J. Am. Chem. Soc., 2016, 138(34): 10968.

doi: 10.1021/jacs.6b05302
[34]
Atkins J H, Gershell L J. Nat. Rev. Cancer, 2002, 2(9): 645.

doi: 10.1038/nrc900
[35]
Bevernaegie R, Marcélis L, Laramée-Milette B de Winter J, Robeyns K, Gerbaux P, Hanan G S, Elias B. Inorg. Chem., 2018, 57(3): 1356.

doi: 10.1021/acs.inorgchem.7b02778 pmid: 29336560
[36]
Bevernaegie R, Doix B, Bastien E, Diman A, Decottignies A, Feron O, Elias B. J. Am. Chem. Soc., 2019, 141(46): 18486.

doi: 10.1021/jacs.9b07723 pmid: 31644286
[37]
Huang H Y, Banerjee S, Qiu K Q, Zhang P Y, Blacque O, Malcomson T, Paterson M J, Clarkson G J, Staniforth M, Stavros V G, Gasser G, Chao H, Sadler P J. Nat. Chem., 2019, 11(11): 1041.

doi: 10.1038/s41557-019-0328-4
[38]
Kuang S, Sun L L, Zhang X R, Liao X X, Rees T W, Zeng L L, Chen Y, Zhang X T, Ji L N, Chao H. Angew. Chem. Int. Ed., 2020, 59(46): 20697.

doi: 10.1002/anie.v59.46
[39]
Celli J P, Spring B Q, Rizvi I, Evans C L, Samkoe K S, Verma S, Pogue B W, Hasan T. Chem. Rev., 2010, 110(5): 2795.

doi: 10.1021/cr900300p
[40]
Li Y, Tan C P, Zhang W, He L, Ji L N, Mao Z W. Biomaterials, 2015, 39: 95.

doi: 10.1016/j.biomaterials.2014.10.070
[41]
Han K, Lei Q, Wang S B, Hu J J, Qiu W X, Zhu J Y, Yin W N, Luo X, Zhang X Z. Adv. Funct. Mater., 2015, 25(20): 2961.

doi: 10.1002/adfm.201500590
[42]
Huang H Y, Yu B L, Zhang P Y, Huang J J, Chen Y, Gasser G, Ji L N, Chao H. Angew. Chem. Int. Ed., 2015, 54(47): 14049.

doi: 10.1002/anie.201507800
[43]
Fulda S, Galluzzi L, Kroemer G. Nat. Rev. Drug Discov., 2010, 9(6): 447.

doi: 10.1038/nrd3137
[44]
Saftig P, Klumperman J. Nat. Rev. Mol. Cell Biol., 2009, 10(9): 623.
[45]
Lv W, Zhang Z, Zhang K Y, Yang H R, Liu S J, Xu A Q, Guo S, Zhao Q, Huang W. Angew. Chem. Int. Ed., 2016, 55(34): 9947.

doi: 10.1002/anie.201604130
[46]
Guo S, Han M P, Chen R Z, Zhuang Y L, Zou L, Liu S J, Huang W, Zhao Q. Sci. China Chem., 2019, 62(12): 1639.

doi: 10.1007/s11426-019-9583-4
[47]
de Rosa F S, Bentley M V L B. Pharm. Res., 2000, 17(12): 1447.

doi: 10.1023/A:1007612905378
[48]
Lovell J F, Liu T W B, Chen J, Zheng G. Chem. Rev., 2010, 110(5): 2839.

doi: 10.1021/cr900236h
[49]
Liu J P, Chen Y, Li G Y, Zhang P Y, Jin C Z, Zeng L L, Ji L N, Chao H. Biomaterials, 2015, 56: 140.

doi: 10.1016/j.biomaterials.2015.04.002
[50]
Fan W P, Huang P, Chen X Y. Chem. Soc. Rev., 2016, 45(23): 6488.

doi: 10.1039/C6CS00616G
[51]
Hu Q L, Gao M, Feng G X, Liu B. Angew. Chem. Int. Ed., 2014, 53(51): 14225.

doi: 10.1002/anie.v53.51
[52]
Liu J P, Jin C Z, Yuan B, Liu X G, Chen Y, Ji L N, Chao H. Chem. Commun., 2017, 53(12): 2052.

doi: 10.1039/C6CC10015E
[53]
Pathak R K, Marrache S, Harn D A, Dhar S. ACS Chem. Biol., 2014, 9(5): 1178.

doi: 10.1021/cb400944y
[54]
Zhou X, Chen R H, Yu Z H, Li R, Li J J, Zhao X P, Song S L, Liu J J, Huang G. Mol. Cancer, 2015, 14(1): 63.

doi: 10.1186/s12943-015-0331-3
[55]
Liu J P, Jin C Z, Yuan B, Chen Y, Liu X G, Ji L N, Chao H. Chem. Commun., 2017, 53(71): 9878.

doi: 10.1039/C7CC05518H
[56]
He L, Zhang M F, Pan Z Y, Wang K N, Zhao Z J, Li Y, Mao Z W. Chem. Commun., 2019, 55(70): 10472.

doi: 10.1039/C9CC04871E
[57]
Xing L, Gong J H, Wang Y, Zhu Y, Huang Z J, Zhao J, Li F, Wang J H, Wen H, Jiang H L. Biomaterials, 2019, 206: 170.

doi: S0142-9612(19)30171-1 pmid: 30939409
[58]
Yang S C, Tang Z H, Hu C Y, Zhang D W, Shen N, Yu H Y, Chen X S. Adv. Mater., 2019, 31(11): 1805955.

doi: 10.1002/adma.v31.11
[59]
Yu W Y, Liu T, Zhang M K, Wang Z X, Ye J J, Li C X, Liu W L, Li R Q, Feng J, Zhang X Z. ACS Nano, 2019, 13: 1784.
[60]
Fan W P, Bu W B, Shen B, He Q J, Cui Z W, Liu Y Y, Zheng X P, Zhao K L, Shi J L. Adv. Mater., 2015, 27(28): 4155.

doi: 10.1002/adma.v27.28
[61]
Song X J, Feng L Z, Liang C, Yang K, Liu Z. Nano Lett., 2016, 16(10): 6145.

doi: 10.1021/acs.nanolett.6b02365
[62]
Liu W L, Liu T, Zou M Z, Yu W Y, Li C X, He Z Y, Zhang M K, Liu M D, Li Z H, Feng J, Zhang X Z. Adv. Mater., 2018, 30(35): 1802006.

doi: 10.1002/adma.v30.35
[63]
Zheng D W, Li B, Li C X, Fan J X, Lei Q, Li C, Xu Z S, Zhang X Z. ACS Nano, 2016, 10(9): 8715.

doi: 10.1021/acsnano.6b04156
[64]
Xu S T, Zhu X Y, Zhang C, Huang W, Zhou Y F, Yan D Y. Nat. Commun., 2018, 9(1): 2053.

doi: 10.1038/s41467-018-04318-1
[65]
Wang F, Liu X G. Chem. Soc. Rev., 2009, 38(4): 976.

doi: 10.1039/b809132n
[66]
Haase M, Schäfer H. Angew. Chem. Int. Ed., 2011, 50(26): 5808.

doi: 10.1002/anie.v50.26
[67]
Gai S L, Li C X, Yang P P, Lin J. Chem. Rev., 2014, 114(4): 2343.

doi: 10.1021/cr4001594
[68]
Han S Y, Deng R R, Xie X J, Liu X G. Angew. Chem. Int. Ed., 2014, 53(44): 11702.

doi: 10.1002/anie.201403408
[69]
Liu X G, Yan C H, Capobianco J A. Chem. Soc. Rev., 2015, 44(6): 1299.

doi: 10.1039/C5CS90009C
[70]
Zhao J, Sun S C, Li X Y, Zhang W J, Gou S H. ACS Appl. Bio Mater., 2020, 3(1): 252.

doi: 10.1021/acsabm.9b00774
[71]
Winter A, Schubert U S. Chem. Soc. Rev., 2016, 45(19): 5311.

doi: 10.1039/C6CS00182C
[72]
Feng Z Y, Tao P, Zou L, Gao P L, Liu Y, Liu X, Wang H, Liu S J, Dong Q C, Li J, Xu B S, Huang W, Wong W Y, Zhao Q. ACS Appl. Mater. Interfaces, 2017, 9(34): 28319.

doi: 10.1021/acsami.7b09721
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[10] Liang Aihui, Huang Gui, Wang Zhiping, Chen Shuiliang, Hou Haoqing. Polymer Phosphorescent Materials with Iridium Complexes and Their Electroluminescent Properties [J]. Progress in Chemistry, 2016, 28(4): 471-481.
[11] Wang Dongdong, Dong Hua, Lei Xiaoli, Yu Yue, Jiao Bo, Wu Zhaoxin. Iridium Complexes for Triplet Photosensitizer [J]. Progress in Chemistry, 2015, 27(5): 492-502.
[12] Liu Tao, Sun Lining, Liu Zheng, Qiu Yannan, Shi Liyi. Rare-Earth Upconversion Nanophosphors [J]. Progress in Chemistry, 2012, 24(0203): 304-317.
[13] Tao Ran, Qiao Juan, Duan Lian, Qiu Yong. Blue Phosphorescence Materials for Organic Light-Emitting Diodes [J]. Progress in Chemistry, 2010, 22(12): 2255-2267.
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