光敏剂在光动力治疗中的研究进展

doi:10.3969/j.issn.1007-2861.2017.01.007

摘要/Abstract

摘要：

对光动力治疗(photodynamic therapy, PDT) 中常用的光敏剂进行了综述. 光动力治疗自问世以来, 已被广泛应用于肿瘤以及非肿瘤疾病的治疗. 在光化学反应中, 能够被光照激活并把能量传递给反应物, 而本身并不发生反应的物质被称为光敏剂. 光敏剂作为PDT 的一个重要影响因素, 其研究进展对于PDT 的发展起着非常重要的作用. 光敏剂大体分为三代:第一代以血卟啉衍生物为主, 第二代以卟啉、卟吩为代表, 第三代是在第二代的基础上进行化学基团修饰. 经过几十年的发展, 光敏剂的化学性质更加稳定, 副作用更加小.

关键词: 上转换纳米颗粒, 酞菁, 卟啉, 光动力治疗, 光敏剂

Abstract:

This paper reviews the main types of photosensitizers in photodynamic therapy(PDT). PDT has been widely used in the treatment of tumors and non neoplastic diseases since its invention. In a photochemical reaction, a material is called photosensitizer if it can be activated by light with energy transferred to reactants without reaction. Photosensitizer is an important impact factor in PDT, and its research progress is important in the development of PDT. Photosensitizer has three generations: the first dominated by hematoporphyrin derivative, the second represented by porphyrin and porphin, and the third being modification of the second generation chemical groups. After decades of development, chemical properties of photosensitizer has become stable with less side effects.

Key words: photodynamic therapy , phthalocyanin , porphyrin , upconversion nanoparticles, photosensitizer

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 Xiaobo, ZHENG Yinghong, YANG Liming. Advancement of photosensitizers for photodynamic therapy[J]. Journal of Shanghai University（Natural Science Edition）, 2017, 23(2): 169-178.

参考文献

[1] Moan J, Peng Q. An outline of the hundred-year history of PDT [J]. Anticancer Research, 2003, 23(5A): 3591-3600.
[2] Von Tappeiner H, Jodlbauer A. Uber die wirkung der photodynamischen (fluorescierenden) stoffe auf protozoen und enzyme [J]. Dtsch Arch Klin Med, 1904, 80: 427-487.
[3] Abrahamse H, Hamblin M R. New photosensitizers for photodynamic therapy [J]. The Biochemical Journal, 2016, 473(4): 347-364.
[4] Agostinis P, Berg K, Cengel K A, et al. Photodynamic therapy of cancer: an update [J]. CA: Cancer Journal for Clinicians, 2001, 61(4): 250-281.
[5] Wong T W, Wang Y Y, Sheu H M, et al. Bactericidal effects of toluidine blue-mediated photodynamic action on Vibrio vulnificus [J]. Antimicrobial Agents and Chemotherapy, 2005, 49(3): 895-902.
[6] Pogue B W, O’hara J A, Demidenko E, et al. Photodynamic therapy with verteporfin in the radiation-induced fibrosarcoma-1 tumor causes enhanced radiation sensitivity [J]. Cancer Research, 2003, 63(5): 1025-1033.
[7] Foote C S. Mechanisms of photosensitized oxidation [J]. Science, 1968, 162(3857): 963-970.
[8] Allison R, Mang T, Hewson G, et al. Photodynamic therapy for chest wall progression from breast carcinoma is an underutilized treatment modality [J]. Cancer, 2001, 91(1): 1-8.
[9] Cortese D A, Edell E S, Kinsey J H. Photodynamic therapy for early stage squamous cell carcinoma of the lung [J]. Mayo Clinic Proceedings, 1997, 72(7): 595-602.
[10] 刘端祺, 刘慧龙, 介雅慧, 等. 光动力学疗法治疗上消化道癌的临床研究[J]. 中国激光医学杂志, 2007, 16(4): 223-227.
[11] Panjehpour M, Overholt B F. Porfimer sodium photodynamic therapy for management of Barrett’s esophagus with high-grade dysplasia [J]. Lasers in Surgery and Medicine, 2006, 38(5): 390-395.
[12] Allison R R, Zervos E, Sibata C H. Cholangiocarcinoma: an emerging indication for photodynamic therapy [J]. Photodiagnosis and Photodynamic Therapy, 2009, 6(2): 84-92.
[13] Nseyo U O, DeHaven J, Dougherty T J, et al. Photodynamic therapy (PDT) in the treatment of patients with resistant superficial bladder cancer: a long term experience [J]. Journal of Clinical Laser Medicine & Surgery, 1998, 16(1): 61-68.
[14] Peng Q, Warloe T, Berg K, et al. 5-aminolevulinic acid-based photodynamic therapy [J]. Cancer, 1997, 79(12): 2282-2308.
[15] Kennedy J C, Pottier R H, Pross D C. Photodynamic therapy with endogenous protoporphyrin Ⅸ: basic principles and present clinical experience [J]. Journal of Photochemistry and Photobiology B: Biology, 1990, 6(1): 143-148.
[16] Frank R G, Bos J D. Photodynamic therapy for condylomata acuminata with local application of 5-aminolevulinic acid [J]. Genitourinary Medicine, 1996, 72(1): 70-71.

[17] Smits T, Van Laarhoven A I M, Staassen A, et al. Induction of protoporphyrin Ⅸby aminolaevulinic acid in actinic keratosis, psoriasis and normal skin: preferential porphyrin enrichment in differentiated cells [J]. British Journal of Dermatology, 2009, 160(4): 849-857.
[18] Ma L, Xiang L H, Yu B, et al. Low-dose topical 5-aminolevulinic acid photodynamic therapy in the treatment of different severity of acne vulgaris [J]. Photodiagnosis and Photodynamic Therapy, 2013, 10(4): 583-590.
[19] Fink-Puches R, Soyer H P, Hofer A, et al. Long-term follow-up and histological changes of superficial nonmelanoma skin cancers treated with topical d-aminolevulinic acid photodynamic therapy [J]. Archives of Dermatology, 1998, 134(7): 821-826.
[20] Fernandez-Guarino M. Emerging treatment options for early mycosis fungoides [J]. Clinical, Cosmetic and Investigational Dermatology, 2013, 6: 61-69.
[21] Karrer S, Kohl E, Feise K, et al. Photodynamic therapy for skin rejuvenation: review and summary of the literature—results of a consensus conference of an expert group for aesthetic photodynamic therapy [J]. Journal Der Deutschen Dermatologischen Gesellschaft, 2013, 11(2): 137-148.
[22] 许德余, 殷祥生, 陈文晖, 等. 肿瘤光化学诊治新药癌光啉(PsD-007)的研究[J]. 中国医药工业杂志, 1989(10): 440-446.
[23] 顾瑛, 李峻亨. 血啉甲醚用于光动力疗法治疗鲜红斑痣的初步临床研究[J]. 中国激光医学杂志, 1996, 5(4): 201-204.
[24] 王伟, 李辉, 李家泽, 等. 肺癌组织血卟啉单甲醚激光诱发药物荧光与激光诱发自体荧光的光谱区别[J]. 中国激光医学杂志, 2003, 12(4): 243-246.
[25] 刘慧龙, 刘端祺, 介雅慧, 等. 三种光敏剂介导的光动力疗法治疗上消化道肿瘤的疗效比较研究[J]. 中国激光医学杂志, 2011, 20(6): 359-365.
[26] Nakashizuka T, Mori K, Hayashi N, et al. Retreatment effect of NPe6 photodynamic therapy on the normal primate macula [J]. Retina, 2001, 21(5): 493-498.
[27] Kujundˇzi´cm, Vogl T J, Stimac D, et al. A phase Ⅱ safety and effect on time to tumor progression study of intratumoral light infusion technology using talaporfin sodium in patients with metastatic colorectal cancer [J]. Journal of Surgical Oncology, 2007, 96(6): 518-524.
[28] 刘岩岩, 王雪松, 张宝文. 竹红菌素类光动力药物[J]. 化学进展, 2008, 20(9): 1345-1352.
[29] Zhenjun D, Lown J W. Hypocrellins and their use in photosensitization [J]. Photochemistry and Photobiology, 1990, 52(3): 609-616.
[30] Estey E P, Brown K, Diwu Z, et al. Hypocrellins as photosensitizers for photodynamic therapy: a screening evaluation and pharmacokinetic study [J]. Cancer Chemotherapy and Pharmacology, 1996, 37(4): 343-350.
[31] Miller G G, Brown K, Ballangrud A M, et al. Preclinical assessment of hypocrellin B and hypocrellin B derivatives as sensitizers for photodynamic therapy of cancer: progress update [J]. Photochemistry and Photobiology, 1997, 65(4): 714-722.
[32] 梁巧丽, 高宏成. 金丝桃素的研究进展[J]. 中草药, 1999, 30(9): 705-708.
[33] Kang B Y, Chung S W, Kim T S. Inhibition of interleukin-12 production in lipopolysaccharideactivated mouse macrophages by hpyericin, an active component of hypericum perforatum [J]. Planta Medica, 2001, 67(4): 364-366.

[34] Park J, English D S, Wannemuehler Y, et al. The role of oxygen in the antiviral activity of hypericin and hypocrellin [J]. Photochemistry and Photobiology, 1998, 68(4): 593-597.
[35] Mirossay L, Mirossay A, Kocisova E, et al. Hypericin-induced phototoxicity of human leukemic cell line HL-60 is potentiated by omeprazole, an inhibitor of H+ K+-ATPase and 5’-(N, N-dimethyl)-amiloride, an inhibitor of Na+/H+ exchanger [J]. Physiological Research, 1998, 48(2): 135-141.
[36] Liu C D, Kwan D, Saxton R E, et al. Hypericin and photodynamic therapy decreases human pancreatic cancer in vitro and in vivo [J]. Journal of Surgical Research, 2000, 93(1): 137-143.
[37] Kamuhabwa A R, Agostinis P, D’Hallewin M A, et al. Photodynamic activity of hypericin in human urinary bladder carcinoma cells [J]. Anticancer Research, 1999, 20(4): 2579-2584.
[38] Chen B, De Witte P A. Photodynamic therapy efficacy and tissue distribution of hypericin in a mouse P388 lymphoma tumor model [J]. Cancer Letters, 2000, 150(1): 111-117.
[39] Colasanti A, Kisslinger A, Liuzzi R, et al. Hypericin photosensitization of tumor and metastatic cell lines of human prostate [J]. Journal of Photochemistry and Photobiology B: Biology, 2000, 54(2): 103-107.
[40] Alecu M, Ursaciuc C, Halalau F, et al. Photodynamic treatment of basal cell carcinoma and squamous cell carcinoma with hypericin [J]. Anticancer Research, 1997, 18(6B): 4651-4654.
[41] Ursaciuc C, Cotroceanu C, Berendei I, et al. Ca+-ATPase activity in normal and tumoral murine lymphoid cells; down regulation by protein kinase inhibitor hypericin [J]. Journal of Medicine and Biochemistry, 2000, 4(2): 137-146.
[42] 马晓华, 梁海曼. 姜黄素抗肿瘤作用与诱导肿瘤细胞凋亡的研究概况[J]. 国外医学(肿瘤学分册), 1999, 26(1): 21-23.
[43] 许川山. 中药姜黄素的光谱学特性研究[J]. 激光杂志, 2005, 26(4): 86.
[44] 陈瑞川, 苏金华, 马胜平, 等. 光敏化姜黄素诱导胃癌细胞凋亡[J]. 癌症, 2000, 19(4): 321-324.
[45] 贺桂芳, 李红艳, 徐波, 等. 姜黄素光动力疗法对人宫颈癌H8 细胞的作用[J]. 中国激光医学杂志, 2013 (1): 15-20.
[46] Leite D P V, Paolillo F R, Parmesano T N, et al. Effects of photodynamic therapy with blue light and curcumin as mouth rinse for oral disinfection: a randomized controlled trial [J]. Photomedicine and Laser Surgery, 2014, 32(11): 627-632.
[47] 丁兰兰, 栗立强, 施佳伟, 等. 酞青在光动力治疗中的应用[J]. 无机化学学报, 2013, 29(8): 1591-1598.
[48] Rosenthal I. Phthalocyanines as photodynamic sensitizers [J]. Photochemistry and Photobiology, 1991, 53(6): 859-870.
[49] Filonenko E V, Sokolov V V, Chissov V I, et al. Photodynamic therapy of early esophageal cancer [J]. Photodiagnosis and Photodynamic Therapy, 2008, 5(3): 187-190.
[50] Miller J D, Baron E D, Scull H, et al. Photodynamic therapy with the phthalocyanine photosensitizer Pc4: the case experience with preclinical mechanistic and early clinical—translational studies [J]. Toxicology and Applied Pharmacology, 2007, 224(3): 290-299.
[51] Luan L, Ding L, Zhang W, et al. A naphthalocyanine based near-infrared photosensitizer: synthesis and in vitro photodynamic activities [J]. Bioorganic & Medicinal Chemistry Letters, 2013, 23(13): 3775-3779.

[52] 陈耐生, 薛金萍, 黄金陵. 用于光动力治疗抗癌新药“福大赛因” 的药学与I期临床研究[C]// 中国药学大会暨第十届中国药师周论文集. 2010.
[53] 田泽丹, 许川山, 全学模, 等. 声敏剂与光敏剂的研究进展[J]. 临床超声医学杂志, 2008, 10(1): 14-16.
[54] 许德余, 张浩. 光动力治癌新药血卟啉单甲醚(HMME) 的研究[J]. 中国激光医学杂志, 1993, 2(1): 3-7.
[55] Polo L, Valduga G, Jori G, et al. Low-density lipoprotein receptors in the uptake of tumour photosensitizers by human and rat transformed fibroblasts [J]. The International Journal of Biochemistry & Cell Biology, 2002, 34(1): 10-23.
[56] Staggers N, Mc Casky T, Brazelton N, et al. Nanotechnology: the coming revolution and its implications for consumers, clinicians, and informatics [J]. Nursing Outlook, 2008, 56(5):268-274.
[57] Mroz P, Tegos G P, Gali H, et al. Photodynamic therapy with fullerenes [J]. Photochem Photobiol Sciences, 2007, 6(11): 1139-1149.
[58] Brown E, Allen M, Pyles H, et al. Advancements in using TiO2 bionanoconjugates for precision degradation of intracellular biological structures [J]. Journal of Biomedical Nanotechnology, 2013, 9(4): 539-550.
[59] Huang Y Y, Sharma S K, Dai T, et al. Can nanotechnology potentiate photodynamic therapy? [J]. Nanotechnology Reviews, 2012, 1(2): 111-146.
[60] Gamelin D R, Gudel H U. Upconversion processes in transition metal and rare earth metal systems [M]// Transition metal and rare earth compounds. Berlin: Springer-Verlag, 2001: 1-56.
[61] Lim M E, Lee Y, Zhang Y, et al. Photodynamic inactivation of viruses using upconversion nanoparticles [J]. Biomaterials, 2012, 33(6): 1912-1920.
[62] Idris N M, Gnanasammandhan M K, Zhang J, et al. In vivo photodynamic therapy using upconversion nanoparticles as remote-controlled nanotransducers [J]. Nature Medicine, 2012, 18(10): 1580-1585.
[63] Wang C, Cheng L, Liu Z. Drug delivery with upconversion nanoparticles for multi-functional targeted cancer cell imaging and therapy [J]. Biomaterials, 2011, 32(4): 1110-1120.
[64] Wang Y F, Liu G Y, Sun L D, et al. Nd3+-sensitized upconversion nanophosphors: efficient in vivo bioimaging probes with minimized heating effect [J]. ACS Nano, 2013, 7(8): 7200-7206.
[65] Zhan Q, Qian J, Liang H, et al. Using 915 nm laser excited Tm3+/Er3+/Ho3+-doped NaYbF4 upconversion nanoparticles for in vitro and deeper in vivo bioimaging without overheating irradiation[J]. ACS Nano, 2011, 5(5): 3744-3757.
[66] Zou W, Visser C, Maduro J A, et al. Broadband dye-sensitized upconversion of near-infrared light [J]. Nature Photonics, 2012, 6(8): 560-564.
[67] Jayakumar M K G, Idris N M, Huang K, et al. A paradigm shift in the excitation wavelength of upconversion nanoparticles [J]. Nanoscale, 2014, 6(15): 8441-8443.
[68] Ash D V, Brown S B. New drugs and future developments in photodynamic therapy [J]. European Journal of Cancer, 1993, 29(12): 1781-1783.