TCMePyP的制备及对神经母细胞瘤细胞系SH-SY5Y光动力杀伤作用的研究
|
摘要
在H2TPyP上接入羧基进行修饰,得到TCMePyP。测定了TCMePyP的紫外-可见吸收光谱、荧光光谱。观察了SH-SY5Y细胞对新型卟啉化合物的摄取情况和光照条件下细胞内活性氧物质(Reactive oxygen species,ROS)的变化情况。进一步考察了新型卟啉化合物对神经母细胞瘤细胞系SH-SY5Y的抑制作用。结果表明:TCMePyP具备良好光敏药物的特性,脂溶性和水溶性良好;在可见光区有较强吸收;光动力条件下活性氧物质ROS随光照时间在一定范围内增加;TCMePyP对SH-SY5Y肿瘤细胞的增殖有抑制作用,杀伤效果明显;发射的荧光在SH-SY5Y肿瘤细胞内可以定位成像。因此,TCMePyP具有较好的医药应用前景。
Carboxyl was connected to H_2TPyP to modify and obtained the TCMePyP.UV-Vis absorption spectra and fluorescence spectra of TCMePyP were determined.The uptake of new porphyrin compounds in SHSY5 Ycells and the changes of intracellular ROS(reactive oxygen species)under radiation were observed.The inhibitory effect of new porphyrin compounds on neuroblastoma cell line SH-SY5 Y was further investigated.The results showed that TCMePyP has the characteristics of effective photosensitizer:good lipid solubility and water solubility,strong absorption in visible light area.ROS increased with the radiation time under the photodynamic condition.It has inhibitory effect on the proliferation of SH-SY5 Ytumor cells,and the killing effect is obvious.The emitted fluorescence can be located in SH-SY5 Ytumor cells.In a word,TCMePyP has good prospects for medical applications.
Carboxyl was connected to H_2TPyP to modify and obtained the TCMePyP.UV-Vis absorption spectra and fluorescence spectra of TCMePyP were determined.The uptake of new porphyrin compounds in SHSY5 Ycells and the changes of intracellular ROS(reactive oxygen species)under radiation were observed.The inhibitory effect of new porphyrin compounds on neuroblastoma cell line SH-SY5 Y was further investigated.The results showed that TCMePyP has the characteristics of effective photosensitizer:good lipid solubility and water solubility,strong absorption in visible light area.ROS increased with the radiation time under the photodynamic condition.It has inhibitory effect on the proliferation of SH-SY5 Ytumor cells,and the killing effect is obvious.The emitted fluorescence can be located in SH-SY5 Ytumor cells.In a word,TCMePyP has good prospects for medical applications.
引文
[1]Tsubota S,Kadomatsu K.Origin and mechanism of neuroblastoma[J].Oncoscience,2017,4(7):70-72.
[2]Moroz V,Machin D,Faldum A,Hero B,Iehara T,Mosseri V,Ladenstein R,Bernardi B D,Rubie H,Berthold F,Matthay K K,Monclair T,Ambros P F,Pearson A D J,London W B.Changes over three decades in outcome and the prognostic influence of age-at-diagnosis in young patients with neuroblastoma:a report from the International Neuroblastoma Risk Group Project[J].European Journal of Cancer,2011,47(4):561-571.
[3]Barak B A,Golan H,Waldman D,Arkovitz M S.Surgical treatment of neuroblastoma[J].Israel Medical Association Journal,2017,19(11):691-695.
[4]胡月,赵强,乔晓红,李杰,李璋琳,王景福,闰杰,曹嫣娜,王会娟.Ⅳ期神经母细胞瘤手术切除范围对生存率的影响[J].中华小儿外科杂志,2013,34(2):81-85.Hu Y,Zhao Q,Qiao X H,Li J,Li Z L,Wang J F,Yan J,Cao Y N,Wang H J.The impact of surgical intervention on survival in stageⅣneuroblastoma[J].Chinese Journal of Pediatric Surgery,2013,34(2):81-85.
[5]Maris J M,Hogarty M D,Bagatell R,Cohn S L.Neuroblastoma[J].Lance,2007,369(9579):2106-2122.
[6]Kou J,Dou D,Yang L.Porphyrin photosensitizers in photodynamic therapy and its applications[J].Oncotarget,2017,8(46):81591-81603.
[7]Allison R R,Moghissi K.Photodynamic therapy(PDT):PDT mechanisms[J].Clincal Endoscopy,2013,46(1):24-29.
[8]Rahman T,Hosen I,Islam M M T,Shekhar H U.Oxidative stress and human health[J].Biotechnology Advance,2012,3:997-1019.
[9]Jiang B,Dong Y,He H,Han C.Application of pirarubicin photosensitizer fluorescence cystoscopy in early detection of bladder cancer[J].Oncology Letters,2017,14(3):3309-3312.
[10]韩晓博,郑英虹,杨力明.光敏剂在光动力治疗中的研究进展[J].上海大学学报自然科学版,2017,23(2):169-178.Han X B,Zheng Y H,Yang L M.Advancement of photosensitizers for photodynamic therapy[J].Journal Of Shanghai University(Natural Science),2017,23(2):169-178.
[11]Vicente M D,Smith K M.Syntheses and functionalizations of porphyrin macrocycles[J].Current Organic Synthesis,2014,11(1):3-28.
[12]Bonnett R.Photosensitizers of the porphyrin and phthalocyanine series for photodynamic[J].Chemical Society Reviews,1995,26(37):19-33.
[13]Banala S,Wurst K,Krutle B.Panchromaticπ-extended porphyrins from conjugation with quinones[J].Chempluschem,2016,81(5):477-488.
[14]Militello M P,Hernández-Ramírez R E,Lijanova I V,Prevital C M,Bertolotti S G,Arbeloa E M.Novel PAM-AM dendrimers with porphyrin core as potential photosensitizers for PDT applications[J].Journal of Photochemistry and Photobiology A:Chemistry,2018,353:71-76.
[15]Xiao X,Sun J S,Jiang J Z.X-Ray structure of a porphyrin-tetramethylcucurbit[6]uril supramolecular polymer[J].Chemistry-A European Journal,2013,19(50):16891-16896.
[16]李东红,李鹏熙,蒋宗林,郭林峰.新型靶向光敏剂诱导-细胞光氧化行为的研究[J].肿瘤学杂志,2015,19(7):539-543.Li D H,Li P X,Jiang Z L,Guo L F.Reserch on the photooxidative action in Hep-2cells Induced by a novel targeting photosensitizer[J].Journal of Chinese oncology,2015,19(7):539-543.
[17]Gao Z Z,Zhang J,Sun N N,Huang Y,Tao Z,Xiao X,Jiang J Z.Hyperbranched supramolecular polymer constructed from twisted cucurbit[14]uril and porphyrin via host-guest interactions[J].Organic Chemistry Frontiers,2016,3:1144-1148.
[18]杨宝峰,陈建国.药理学[M].北京:人民卫生出版社,2015.4-5.Yang B F,Chen J G.Pharmacology[M].Beijing:People’s Medical Publishing House,2015.4-5.
[19]Chiol I C,Tuveson D A.ROS in cancer:the burning question[J].Trends in Molecular Medicine,2017,23(5):411-429.
[20]Bacellar I O,Tsubone T M,Pavani C,Baptista M S.Photodynamic efficiency:from molecular photochemistry to cell death[J].International Journal of Solecular Sciences,2015,16(9):20523-20559.
[21]Bashiri H,Jalali H M,Rasa H.Determination of intracellular levels of reactive oxygen species using the 2,7-dichlorofluorescein diacetate assay by kinetic Monte Carlo simulation[J].Progress in Reaction Kinetics and Mechanism,2014,39(3):281-291.
[22]Lunagariya M V,Thakor K P,Waghela B N,Vaidya F U,Pathak C,Patel M N.Design,synthesis,MTT assay,DNA interaction studies of platinum(Ⅱ)complexes[J].Journal of Biomolecular Structure and Dynamics,2018,36(1):14-31.
[2]Moroz V,Machin D,Faldum A,Hero B,Iehara T,Mosseri V,Ladenstein R,Bernardi B D,Rubie H,Berthold F,Matthay K K,Monclair T,Ambros P F,Pearson A D J,London W B.Changes over three decades in outcome and the prognostic influence of age-at-diagnosis in young patients with neuroblastoma:a report from the International Neuroblastoma Risk Group Project[J].European Journal of Cancer,2011,47(4):561-571.
[3]Barak B A,Golan H,Waldman D,Arkovitz M S.Surgical treatment of neuroblastoma[J].Israel Medical Association Journal,2017,19(11):691-695.
[4]胡月,赵强,乔晓红,李杰,李璋琳,王景福,闰杰,曹嫣娜,王会娟.Ⅳ期神经母细胞瘤手术切除范围对生存率的影响[J].中华小儿外科杂志,2013,34(2):81-85.Hu Y,Zhao Q,Qiao X H,Li J,Li Z L,Wang J F,Yan J,Cao Y N,Wang H J.The impact of surgical intervention on survival in stageⅣneuroblastoma[J].Chinese Journal of Pediatric Surgery,2013,34(2):81-85.
[5]Maris J M,Hogarty M D,Bagatell R,Cohn S L.Neuroblastoma[J].Lance,2007,369(9579):2106-2122.
[6]Kou J,Dou D,Yang L.Porphyrin photosensitizers in photodynamic therapy and its applications[J].Oncotarget,2017,8(46):81591-81603.
[7]Allison R R,Moghissi K.Photodynamic therapy(PDT):PDT mechanisms[J].Clincal Endoscopy,2013,46(1):24-29.
[8]Rahman T,Hosen I,Islam M M T,Shekhar H U.Oxidative stress and human health[J].Biotechnology Advance,2012,3:997-1019.
[9]Jiang B,Dong Y,He H,Han C.Application of pirarubicin photosensitizer fluorescence cystoscopy in early detection of bladder cancer[J].Oncology Letters,2017,14(3):3309-3312.
[10]韩晓博,郑英虹,杨力明.光敏剂在光动力治疗中的研究进展[J].上海大学学报自然科学版,2017,23(2):169-178.Han X B,Zheng Y H,Yang L M.Advancement of photosensitizers for photodynamic therapy[J].Journal Of Shanghai University(Natural Science),2017,23(2):169-178.
[11]Vicente M D,Smith K M.Syntheses and functionalizations of porphyrin macrocycles[J].Current Organic Synthesis,2014,11(1):3-28.
[12]Bonnett R.Photosensitizers of the porphyrin and phthalocyanine series for photodynamic[J].Chemical Society Reviews,1995,26(37):19-33.
[13]Banala S,Wurst K,Krutle B.Panchromaticπ-extended porphyrins from conjugation with quinones[J].Chempluschem,2016,81(5):477-488.
[14]Militello M P,Hernández-Ramírez R E,Lijanova I V,Prevital C M,Bertolotti S G,Arbeloa E M.Novel PAM-AM dendrimers with porphyrin core as potential photosensitizers for PDT applications[J].Journal of Photochemistry and Photobiology A:Chemistry,2018,353:71-76.
[15]Xiao X,Sun J S,Jiang J Z.X-Ray structure of a porphyrin-tetramethylcucurbit[6]uril supramolecular polymer[J].Chemistry-A European Journal,2013,19(50):16891-16896.
[16]李东红,李鹏熙,蒋宗林,郭林峰.新型靶向光敏剂诱导-细胞光氧化行为的研究[J].肿瘤学杂志,2015,19(7):539-543.Li D H,Li P X,Jiang Z L,Guo L F.Reserch on the photooxidative action in Hep-2cells Induced by a novel targeting photosensitizer[J].Journal of Chinese oncology,2015,19(7):539-543.
[17]Gao Z Z,Zhang J,Sun N N,Huang Y,Tao Z,Xiao X,Jiang J Z.Hyperbranched supramolecular polymer constructed from twisted cucurbit[14]uril and porphyrin via host-guest interactions[J].Organic Chemistry Frontiers,2016,3:1144-1148.
[18]杨宝峰,陈建国.药理学[M].北京:人民卫生出版社,2015.4-5.Yang B F,Chen J G.Pharmacology[M].Beijing:People’s Medical Publishing House,2015.4-5.
[19]Chiol I C,Tuveson D A.ROS in cancer:the burning question[J].Trends in Molecular Medicine,2017,23(5):411-429.
[20]Bacellar I O,Tsubone T M,Pavani C,Baptista M S.Photodynamic efficiency:from molecular photochemistry to cell death[J].International Journal of Solecular Sciences,2015,16(9):20523-20559.
[21]Bashiri H,Jalali H M,Rasa H.Determination of intracellular levels of reactive oxygen species using the 2,7-dichlorofluorescein diacetate assay by kinetic Monte Carlo simulation[J].Progress in Reaction Kinetics and Mechanism,2014,39(3):281-291.
[22]Lunagariya M V,Thakor K P,Waghela B N,Vaidya F U,Pathak C,Patel M N.Design,synthesis,MTT assay,DNA interaction studies of platinum(Ⅱ)complexes[J].Journal of Biomolecular Structure and Dynamics,2018,36(1):14-31.