Preparation of compound high water-soluble chlorin-based photosensitizer and its photodynamic cell therapy performance test

LI Hongyu; XU Han; HUANG Yangyang

doi:10.3969/j.issn.2096-3882.2023.01.005

Journal of Xuzhou Medical University > 2023 > 43(1): 27-32. > DOI: 10.3969/j.issn.2096-3882.2023.01.005

LI Hongyu, XU Han, HUANG Yangyang. Preparation of compound high water-soluble chlorin-based photosensitizer and its photodynamic cell therapy performance test[J]. Journal of Xuzhou Medical University, 2023, 43(1): 27-32. DOI: 10.3969/j.issn.2096-3882.2023.01.005

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Preparation of compound high water-soluble chlorin-based photosensitizer and its photodynamic cell therapy performance test

School of Radiation Medicine and Protection, Suzhou Medical College, Soochow University, Suzhou, Jiangsu 215123, China

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Received Date: September 06, 2022
Revised Date: October 09, 2022
Available Online: January 01, 2024

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Objective To explore an easy and convenient strategy to improve the solubility of chlorin e6(Ce6) in aqueous medium and evaluate its photodynamic activity at the cellular level.Methods The highly water-soluble photosensitizer CHCe6 was prepared by supramolecular combination of bionutrient choline(Choline) and photosensitizer Ce6. The photophysical properties of the photosensitizer CHCe6(including UV-Vis absorption spectrum, and singlet oxygen quantum yield) were characterized by spectrometry. The stability of photosensitizers CHCe6 and Ce6 in aqueous medium was analyzed by UV-Vis absorption spectroscopy. The cellular uptakes of photosensitizers CHCe6 and Ce6 by murine triple-negative breast cancer 4T1 tumor cells were analyzed. DHE and AO stainings were conducted to assess the production of reactive oxygen species of photosensitizers CHCe6 and Ce6 and their effects on lysosomal membrane structure. The phototoxicity and dark toxicity of photosensitizers CHCe6 and Ce6 to 4T1 tumor cells were evaluated by cytotoxicity experiments.Results The highly water-soluble photosensitizer CHCe6 was successfully prepared by the supramolecular combination strategy. CHCe6 exhibited high singlet oxygen quantum yield and photostability under low-power LED irradiation. Cellular uptake experiments showed that CHCe6 was effectively internalized by 4T1 tumor cells by a time-dependent manner. DHE and AO stainings further confirmed that CHCe6 efficiently produced reactive oxygen species in 4T1 tumor cells under low-power LED irradiation and rapidly transported to the cytoplasm through the lysosomal membrane disruption. Furthermore, cytotoxicity experiments showed that CHCe6 exhibited lower dark toxicity and higher phototoxicity.Conclusions Compared with Ce6, CHCe6 exhibits higher water solubility, with better photostability and remarkable capacity to produce reactive oxygen species. Upon low-power LED irradiation, CHCe6 can significantly inhibit the growth of murine triple-negative breast cancer 4T1 cells, demonstrating good clinical application potential.
- photodynamic therapy,
- chlorin e6,
- water-soluble,
- breast cancer

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[1]	Chen WQ,Zheng RS,Baade PD,et al.Cancer statistics in China,2015[J].CA Cancer J Clin,2016,66(2):115-132.
[2]	Siegel RL,Miller KD,Jemal A.Cancer statistics,2020[J].CA Cancer J Clin,2020,70(1):7-30.
[3]	Bray F,Jemal A,Grey N,et al.Global cancer transitions according to the human development index (2008-2030):a population-based study[J].Lancet Oncol,2012,13(8):790-801.
[4]	Siegel RL,Miller KD,Jemal A.Cancer statistics,2015[J].CA Cancer J Clin,2015,65(1):5-29.
[5]	Urruticoechea A,Alemany R,Balart J,et al.Recent advances in cancer therapy:an overview[J].Curr Pharm Des,2010,16(1):3-10.
[6]	程亮,汪超,刘庄.功能纳米材料在肿瘤光学治疗中的应用[J].中国肿瘤临床,2014,41(1):18-26.
[7]	Huang XH,Jain PK,El-Sayed IH,et al.Plasmonic photothermal therapy (PPTT) using gold nanoparticles[J].Lasers Med Sci,2008,23(3):217-228.
[8]	Nyman ES,Hynninen PH.Research advances in the use of tetrapyrrolic photosensitizers for photodynamic therapy[J].J Photochem Photobiol B Biol,2004,73(1/2):1-28.
[9]	万勃,邓文婷.光动力疗法的研究进展[J].广东化工,2019,46(7):124-127,119.
[10]	Dobson J,deQueiroz GF,Golding JP.Photodynamic therapy and diagnosis:principles and comparative aspects[J].Vet J,2018,233:8-18.
[11]	Zhen Z,Tang W,Guo C,et al.Ferritin nanocages to encapsulate and deliver photosensitizers for efficient photodynamic therapy against cancer[J].ACS Nano,2013,7(8):6988-6996.
[12]	Li SY,Cheng H,Xie BR,et al.Cancer cell membrane camouflaged cascade bioreactor for cancer targeted starvation and photodynamic therapy[J].ACS Nano,2017,11(7):7006-7018.
[13]	傅乃武.光敏剂研究进展[J].生理科学进展,1992,23(1):36-40.
[14]	Akhlynina TV,Jans DA,Rosenkranz AA,et al.Nuclear targeting of Chlorin e6 enhances its photosensitizing activity[J].J Biol Chem,1997,272(33):20328-20331.
[15]	Wei JP,Li JC,Sun D,et al.A novel theranostic nanoplatform based on Pd@Pt-PEG-Ce6 for enhanced photodynamic therapy by modulating tumor hypoxia microenvironment[J/OL].Adv Funct Mater,2018,28(17):1706310.
[16]	Liu P,Shi L,Zhang HY,et al.Study on progress of research on safety and efficacy of nano-sensitizer induced photodynamic therapy for skin cancer[J].Chin J Laser Med Surg,2018,27(6):404-412.
[17]	Lin JF,Li J,Gopal A,et al.Synthesis of photo-excited Chlorin e6 conjugated silica nanoparticles for enhanced anti-bacterial efficiency to overcome methicillin-resistant staphylococcus aureus[J].Chem Commun (Camb),2019,55(18):2656-2659.
[18]	Agostinis P,Berg K,Cengel KA,et al.Photodynamic therapy of cancer:an update[J].CA Cancer J Clin,2011,61(4):250-281.
[19]	Guo XH,Wang L,Wang SS,et al.Synergistic antiproliferative effect of chemo-phototherapy:synthesis and photodynamic activity evaluation of novel Chlorin e6-artesunate conjugates as antiproliferative agents[J].Bioorg Med Chem Lett,2017,27(19):4548-4551.
[20]	Ryu JH,Jeong YI,Kim HY,et al.Enhanced photosensing and photodynamic treatment of colon cancer cells using methoxy poly(ethylene glycol)-conjugated Chlorin e6[J].J Nanosci Nanotechnol,2018,18(2):1131-1136.
[21]	李晨露,夏芳芳,章阿敏,等.金纳米星负载二氢卟吩e6对肺癌A549细胞的光动力效应[J].中国肿瘤生物治疗杂志,2018,25(4):394-400.
[22]	Sun JH,Zhang W,Zhang DY,et al.Multifunctional mesoporous silica nanoparticles as efficient transporters of doxorubicin andchlorin e6 for chemo-photodynamic combinatorial cancer therapy[J].J Biomater Appl,2018,32(9):1253-1264.
[23]	Ding F,Li HJ,Wang JX,et al.Chlorin e6-encapsulated polyphosphoester based nanocarriers with viscous flow core for effective treatment of pancreatic cancer[J].ACS Appl Mater Interfaces,2015,7(33):18856-18865.
[24]	Tong R,Yala LD,Fan TM,et al.The formulation of aptamer-coated paclitaxel-polylactide nanoconjugates and their targeting to cancer cells[J].Biomaterials,2010,31(11):3043-3053.

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