Low toxic ytterbium complexes of 2,4-dimethoxyhematoporphyrin IX for luminescence diagnostics of tumors
-
Andrey V. Ivanov
, Valerii M. Markushev
Abstract:
This article deals with the creation of new low-toxic photosensitizers on the basis of Ytterbium-2,4-dimethoxyhematoporphyrin IX (Yb-DMHP) and their application for the luminescence diagnostics of cancer. These substances were found to weakly generate singlet oxygen, exhibit pronounced luminescence, and retain the tumor-tropic properties of therapeutic photosensitizers. Basic photophysical properties of Yb-DMHP were studied, and the primary toxicological and pharmacokinetic investigations were performed in the organisms of experimental animals. The 4f-luminescence of Yb-DMHP in the near infrared (NIR) spectral region was observed. Comparative investigations were performed for one of the photodynamic medications which have been approved for clinical application: “Photoditazin”, a diglucosamine salt of chlorin e6. It was shown that the efficiency of singlet oxygen generation is lower by approximately one order of magnitude in the case of Yb-DMHP. The experimental data prove that Yb-DMHP-based substances are promising as non-toxic markers for the luminescence diagnostics of malignant tumors in the NIR spectral range (900–1100 nm), because they are free of the phototoxicity that is typical of conventional porphyrins, while at the same time providing a relatively high luminescence contrast and a selective accumulation in tumor tissue.
Zusammenfassung
Dieser Artikel befasst sich mit der Entwicklung neuer schwach toxischer Photosensibilisatoren auf der Basis von Ytterbium-2,4-Dimethoxyhematoporphyrin IX (Yb-DMHP) und ihrer Anwendung für die Lumineszenzdiagnose von Krebs. Es hat sich gezeigt, dass diese Substanzen nur geringe Mengen an Singulett-Sauerstoff erzeugen, eine ausgeprägte Lumineszenz aufweisen und die tumortropen Eigenschaften von therapeutischen Photosensibilisatoren behalten. Grundlegende photophysikalische Eigenschaften von Yb-DMHP wurden untersucht, primäre toxikologische und pharmakokinetische Untersuchungen in den Organismen von Versuchstieren durchgeführt sowie die 4f-Lumineszenz im nahen Infrarot (NIR)-Spektralbereich beobachtet. Vergleichende Untersuchungen wurden für eines der photodynamischen Medikamente, die für die klinische Anwendung zugelassen sind, durchgeführt: „Photoditazin“, ein Glucosaminsalz des Chlorin e6. Es wurde gezeigt, dass die Effizienz der Erzeugung von Singulett-Sauerstoff bei Yb-DMHP um ungefähr eine Größenordnung geringer ist. Die experimentellen Daten erwiesen sich als vielversprechend und deuten darauf hin, dass Yb-DMHP-basierte Stoffe als ungiftige Marker für die Lumineszenzdiagnostik von malignen Tumoren im NIR-Spektralbereich (900–1100 nm) einsetzbar sind, da sie frei von Phototoxizität sind (die typisch für herkömmliche Porphyrine ist) und gleichzeitig einen relativ hohen Lumineszenzkontrast und eine selektive Anreicherung im Tumorgewebe aufweisen.
This work was supported by the International Science and Technology Center (project no. 3065). The work was partially supported by the Programs of Presidium of Russian Academy of Sciences “Basic Research for Medicine”.
References
[1] Mironov AF. Current state of the chemistry of photosensitizers based on porphyrins and related compounds. In: Golubchikov OA, editor. Advances in porphyrin chemistry. Volume 4. St. Petersburg: BBM; 2004, p. 271–89. [in Russian].Search in Google Scholar
[2] Menezes PFC, Imasato H, Ferreira J, Bagnato VS, Perussi JR. Correlation of cytotoxicity and depth of necrosis of the photoproducts of photogem®. Laser Phys 2007;17(4):461–7.10.1134/S1054660X0704024XSearch in Google Scholar
[3] Solovieva AB, Melik-Nubarov NS, Zhiyentayev TM, Tolstikh PI, Kuleshov II, Aksenova NA, Litmanovich EA, Glagolev NN, Timofeeva VA, Ivanov AV. Development of novel formulations for photodynamic therapy on the basis of amphiphilic polymers and porphyrin photosensitizers. Pluronic influence on photocatalytic activity of porphyrins. Laser Phys 2009;19(4):817–24.10.1134/S1054660X09040410Search in Google Scholar
[4] Tauber AY, Nizhnik AN, Mironov AF, Gaiduk MI, Grigoryants VV. Photochemical activity of porphyrin photosensitizers in the water solutions. Biofizika 1989;34(3):364–7. [in Russian].Search in Google Scholar
[5] Meng JX, Li KF, Yuan J, Zhang LL, Wong WK, Cheah KW. Near-IR luminescence and photophysics of Yb-porphyrinate complexes. Chem Phys Lett 2000;332(3):313–8.10.1016/S0009-2614(00)01252-5Search in Google Scholar
[6] Lobel J, MacDonald IJ, Ciesielski MJ, Barone T, Potter WR, Pollina J, Plunkett RJ, Fenstermaker RA, Dougherty TJ. 2-[1-hexyloxyethyl]-2-devinyl pyropheophorbide-a (HPPH) in a nude rat glioma model: implications for photodynamic therapy. Lasers Surg Med 2001;29(5):397–405.10.1002/lsm.10001Search in Google Scholar PubMed
[7] Ivanov AV, Rumyantseva VD, Shchamkhalov KS, Shilov IP. Luminescence diagnostics of malignant tumors in the IR spectral range using Yb-porphyrin metallocomplexes. Laser Phys 2010;20(12):2056–65.10.1134/S1054660X10220032Search in Google Scholar
[8] Ethirajan M, Chen Y, Joshi P, Pandey RK. The role of porphyrin chemistry in tumor imaging and photodynamic therapy. Chem Soc Rev 2011;40(1):340–62.10.1039/B915149BSearch in Google Scholar
[9] Khlebtsov B, Panfilova E, Khanadeev V, Bibikova O, Terentyuk G, Ivanov A, Rumyantseva V, Shilov I, Ryabova A, Loshchenov V, Khlebtsov NG. Nanocomposites containing silica-coated gold-silver nanocages and Yb-2,4-dimethoxyhematoporphyrin: multifunctional capability of IR-luminescence detection, photosensitization, and photothermolysis. ACS Nano 2011;5(9):7077–89.10.1021/nn2017974Search in Google Scholar PubMed
[10] Rumyantseva VD, Mironov AF, Shilov IP, Shchamkhalov KS, Ivanov AV, Barishnikov AY. Yb-complex 2,4-dimethoxyhematoporphyrin IX dipotassium salt as fluorescence label for early diagnostics of cancer. Russian Federation (RF) Patent 2411243; 2011. http://www.freepatent.ru/images/patents/49/2411243/patent-2411243.pdf [Accessed on 22 April, 2013].Search in Google Scholar
[11] Rumyantseva VD, Markushev VM, Panas AI, Shilov IP, Netschajew AV, Sheveleva EV, Mironov AF, Ivanov AV, Baryshnikov AY. Yb-complexes tetrapyrazolilporphyrins as fluorescence label for the diagnostics of malignant tumor. Russian Federation (RF) Patent 2372099; 2009. http://www.freepatent.ru/images/patents/91/2372099/patent-2372099.pdf [Accessed on 23 April 2013].Search in Google Scholar
[12] Eskin VE. Light scattering by polymers solutions and properties of macromolecules. Leningrad: Nauka; 1986. [in Russian].Search in Google Scholar
[13] Levshin LV, Saletsky AM. Optical methods for the study of molecular systems. Volume 1. Molecular Spectroscopy. Moscow: Moscow University Publishing, Moscow State University; 1994. [in Russian].Search in Google Scholar
[14] Sofiina ZP, Syrkin A, Goldin A, Kline A, editors. Experimental evaluation of anti-tumour drugs in the USSR and in the USA. Moscow: “Meditsina” Publishing; 1980.Search in Google Scholar
[15] Shilov I, Shamkhalov K, Zubov B, Pashinin A, Danielian G, Pozhar V. Compact LED-based device for luminescence measurements of porphyrin metal-complexes. In: 17th Symposium on Photonic Measurements 2008: 18th IMEKO TC 2 Symposium on Photonics in Measurements 2008. Proceedings of a meeting held 25–26 August 2008, Prague, Czech Republic. New York: Curran Associates, Inc.; 2009. p. 179. http://toc.proceedings.com/05248webtoc.pdf [Accessed on 2 May 2013].Search in Google Scholar
[16] Alekhin AP, Boleiko GM, Gudkova SA, Markeev AM, Sigarev AA, Toknova VF, Kirilenko AG, Lapshin RV, Kozlov EN, Tetyukhin DV. Synthesis of biocompartable surfaces by means of nanotechnology methods. Nanotechnologies in Russia 2010;5(9–10);696–708.10.1134/S1995078010090144Search in Google Scholar
[17] Dobretsov GE, Syreishchikova TI, Gryzunov YuA, Smolina NV, Komar AA. Features of the binding of the fluorescent probe K-35 to albumin. Biofizika 2010;55(2):213–9.10.1134/S000635091002003XSearch in Google Scholar
[18] Tsvirko M, Korovin Yu, Rusakova N. Ytterbium-porphyrin as a new class of the luminescence labels. J Phys Conf Ser 2007;79:012025.10.1088/1742-6596/79/1/012025Search in Google Scholar
[19] Korovin YV, Rusakova NV, Popkov YA, Dotsenko VP. Luminescence of ytterbium and neodymium in complexes with bis-macrocyclic ligands. J Appl Spectrosc 2002;69(6):841–4.10.1023/A:1022454202549Search in Google Scholar
[20] Osin NS, Ivanovskaya NP, Sukhin GM. Perspectives of compounds with long luminescence decay times for tumor diagnosis. Almanac Clin Med 2008;17(1):69. [in Russian].Search in Google Scholar
[21] Henderson BW, Dougherty TJ, editors. Photodynamic therapy: basic principles and clinical applications. New York: Marcel Dekker, Inc.; 1992.Search in Google Scholar
[22] Dreaden EC, Mackey MA, Huang X, Kang B, El-Sayed MA. Beating cancer in multiple ways using nanogold. Chem Soc Rev 2011;40(7):3391–404.10.1039/c0cs00180eSearch in Google Scholar
[23] Pitsillides CM, Joe EK, Wei X, Anderson RR, Lin CP. Selective cell targeting with light-absorbing microparticles and nanoparticles. Biophys J 2003;84(6):4023–32.10.1016/S0006-3495(03)75128-5Search in Google Scholar
©2013 by Walter de Gruyter Berlin Boston
Articles in the same Issue
- Masthead
- Masthead
- Editorial
- Medical use of lasers and photonics in Russia – Therapeutic applications
- Editorial note
- Welcoming address to new Editorial Board Members
- Magazine section
- Snapshots
- Original contributions
- Low toxic ytterbium complexes of 2,4-dimethoxyhematoporphyrin IX for luminescence diagnostics of tumors
- Polymers as enhancers of photodynamic activity of chlorin photosensitizers for photodynamic therapy
- Modification of the mechanical and chemical properties of dental enamel using Er laser radiation with sub-ablative energy density
- Investigation on light-assisted preventive effects on dentin erosion
- Preliminary research reports
- Technique for measuring laser radiation intensity in biological tissues
- Laser-based non-invasive spectrophotometry – An overview of possible medical applications
- Study on the effective ablation volume of microwave ablation of porcine livers
- Short communication
- Percutaneous laser disc decompression: A minimally invasive procedure for the treatment of intervertebral disc prolapse – the Bangladesh perspective/Perkutane Laser-Diskusdekompression: Ein minimal-invasives Verfahren zur Behandlung von Bandscheibenvorfall – Ein Erfahrungsbericht aus Bangladesch
- Press release
- PHOTONICS Interview with Prof. Dr. Waidelich
- Congress report
- LASER safety through international information interchange: An introduction to the International Laser Safety Conference (ILSC®) and report of the “ILSC 2013”
- Congress announcements
- Interdisciplinary Laser Course on Medical Laser Applications (incl. PDT): Basics – Safety (LSO) – Clinical Overview
- Congresses 2013/2014
Articles in the same Issue
- Masthead
- Masthead
- Editorial
- Medical use of lasers and photonics in Russia – Therapeutic applications
- Editorial note
- Welcoming address to new Editorial Board Members
- Magazine section
- Snapshots
- Original contributions
- Low toxic ytterbium complexes of 2,4-dimethoxyhematoporphyrin IX for luminescence diagnostics of tumors
- Polymers as enhancers of photodynamic activity of chlorin photosensitizers for photodynamic therapy
- Modification of the mechanical and chemical properties of dental enamel using Er laser radiation with sub-ablative energy density
- Investigation on light-assisted preventive effects on dentin erosion
- Preliminary research reports
- Technique for measuring laser radiation intensity in biological tissues
- Laser-based non-invasive spectrophotometry – An overview of possible medical applications
- Study on the effective ablation volume of microwave ablation of porcine livers
- Short communication
- Percutaneous laser disc decompression: A minimally invasive procedure for the treatment of intervertebral disc prolapse – the Bangladesh perspective/Perkutane Laser-Diskusdekompression: Ein minimal-invasives Verfahren zur Behandlung von Bandscheibenvorfall – Ein Erfahrungsbericht aus Bangladesch
- Press release
- PHOTONICS Interview with Prof. Dr. Waidelich
- Congress report
- LASER safety through international information interchange: An introduction to the International Laser Safety Conference (ILSC®) and report of the “ILSC 2013”
- Congress announcements
- Interdisciplinary Laser Course on Medical Laser Applications (incl. PDT): Basics – Safety (LSO) – Clinical Overview
- Congresses 2013/2014