LUMINESCENCE DIAGNOSTICS OF TUMORS WITH UPCONVERSION NANOPARTICLES

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  • Authors: Rocheva V.V.1,2, Sholina N.V.1,3,4, Derevyashkin S.P.1,2, Generalova A.N.1,5,6, Nechaev A.V.1,7,8, Khochenkov D.A.1,3,4, Semchishen V.A.1,2, Khaydukov E.V.1,2, Stepanova E.V.9,4, Panchenko V.Y.1,2
  • Affiliations:
    1. Institute of Laser and Information Technologies of the Russian Academy of Sciences
    2. 1 Svyatoozerskaya ul., Shatura, Moskovskaya oblast', 140700, Russian Federation
    3. 1 Svyatoozerskaya ul., Shatura, Moskovskaya oblast', 140700, Russian Federation N.N. Blokhin Russian Cancer Research Center
    4. 24 Kashirskoe shosse, Moscow, 115478, Russian Federation
    5. 1 Svyatoozerskaya ul., Shatura, Moskovskaya oblast', 140700, Russian Federation Shemyakin – Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences
    6. 16/10 Miklukho-Maklaya ul., Moscow, 117997, Russian Federation
    7. 1 Svyatoozerskaya ul., Shatura, Moskovskaya oblast', 140700, Russian Federation Lomonosov Mosсow University of Fine Chemical Technology
    8. 86 Prospekt Vernadskogo, Moscow, 119571, Russian Federation
    9. N.N. Blokhin Russian Cancer Research Center
  • Issue: Vol 44, No 2 (2016)
  • Pages: 227-233
  • Section: ARTICLES
  • URL: https://almclinmed.ru/jour/article/view/341
  • DOI: https://doi.org/10.18786/2072-0505-2016-44-2-227-233
  • ID: 341


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Abstract

Background: To improve quality of surgery in oncology, it is necessary to completely remove the tumor, including its metastases, to minimize injury to normal tissues and to reduce duration of an intervention. Modern methods of detection based on radiological computerized tomography and magnetic resonance imaging can identify a tumor after its volume has become big enough, i.e. it contains more than 10 billion cells. Therefore, an improvement of sensitivity and resolution ability of diagnostic tools to identify early stages of malignant neoplasms seems of utmost importance. Aim: To demonstrate the potential of a new class of anti-Stokes luminescence nanoparticles for deep optical imaging with high contrast of malignant tumors. Materials and methods: Upconversion nanoparticles with narrow dispersion and a  size of 70 to 80  nm, with a  core/shell structure of NaYF4:Yb3+:Tm3+/NaYF4 were used in the study. The nanoparticles have an intensive band of anti-Stokes photoluminescence at a wavelength of 800  nm under irradiation with a  wavelength of 975  nm (both wavelengths are within the transparency window for biological tissues). The conversion coefficient of the excitation radiation into the anti-Stokes luminescence was 9%. To increase the time during which nanoparticles can circulate in blood flow of small animals, the nanoparticles were covered by a  biocompatible amphiphilic polymer shell. As a  tumor model we used Lewis epidermoid carcinoma transfected to mice. Results: We were able to obtain stable water colloids of nanoparticles covered with amphiphilic polymer that could preserve their initial size at least for one month. The use of upconversion nanoparticles with a  hydrophilic shell made of intermittent maleic anhydride and octadecene co-polymer with subsequent coating with diglycidyl polyethylene glycol ether allowed for reduction of non-specific reaction of nanoparticles with plasma proteins. In its turn, it resulted in an increased time of their circulation in blood flow of small animals for up to 1 hour. With the Lewis lung carcinoma transfected to mice model we demonstrated аn in-life transportation of upconversion nanoparticles into the tumor with a  high degree of localization due to a passive EPR effect. The contrast of luminescent signal in the tumor compared to adjacent tissues was at least 70%. The possibility of visualization of upconverted nanoparticles up to 15 mm of biological tissue was shown. Conclusion: The optical imaging techniques with anti-Stokes photoluminescent markers ensure a  high contract real-time detection of tumor tissues that allows for their use for intra-operative diagnostics.

About the authors

V. V. Rocheva

Institute of Laser and Information Technologies of the Russian Academy of Sciences; 1 Svyatoozerskaya ul., Shatura, Moskovskaya oblast',
140700, Russian Federation

Email: khaydukov@mail.ru
PhD Student, Junior Research Fellow, Laboratory for Nonlinear Optics of Surface and Laser-Plasma Processes, Advanced Laser Technologies Division Россия

N. V. Sholina

Institute of Laser and Information Technologies of the Russian Academy of Sciences; 1 Svyatoozerskaya ul., Shatura, Moskovskaya oblast',
140700, Russian Federation
N.N. Blokhin Russian Cancer Research Center; 24 Kashirskoe shosse, Moscow, 115478, Russian Federation

Email: khaydukov@mail.ru
Junior Research Fellow, Laboratory for Nonlinear Optics of Surface and Laser-Plasma Processes, Advanced Laser Technologies Division1 ; Junior Research Fellow, Laboratory of Biomarkers and Mechanisms of Tumor Angiogenesis, Research Institute of Experimental Diagnostics and Tumor Therapy Россия

S. P. Derevyashkin

Institute of Laser and Information Technologies of the Russian Academy of Sciences; 1 Svyatoozerskaya ul., Shatura, Moskovskaya oblast',
140700, Russian Federation

Email: khaydukov@mail.ru
Research Laboratorian, Laboratory for Nonlinear Optics of Surface and Laser-Plasma Processes, Advanced Laser Technologies Division Россия

A. N. Generalova

Institute of Laser and Information Technologies of the Russian Academy of Sciences; 1 Svyatoozerskaya ul., Shatura, Moskovskaya oblast',
140700, Russian Federation
Shemyakin – Ovchinnikov Institute of Bioorganic
Chemistry of the Russian Academy of Sciences;
16/10 Miklukho-Maklaya ul., Moscow, 117997, Russian Federation

Email: khaydukov@mail.ru
PhD (in Chemistry), Senior Research Fellow, Laboratory for Nonlinear Optics of Surface and Laser-Plasma Processes, Advanced Laser Technologies Division1 ; Senior Research Fellow, Polymers for Biology Laboratory Россия

A. V. Nechaev

Institute of Laser and Information Technologies of the Russian Academy of Sciences; 1 Svyatoozerskaya ul., Shatura, Moskovskaya oblast',
140700, Russian Federation
Lomonosov Mosсow University of Fine Chemical Technology; 86 Prospekt Vernadskogo, Moscow, 119571, Russian Federation

Email: khaydukov@mail.ru
PhD (in Chemistry), Laboratory for Nonlinear Optics of Surface and Laser-Plasma Processes, Advanced Laser Technologies Division1 ; Associate Professor, Chair of Chemistry and Technology of Synthetic Biologically Active Substances Россия

D. A. Khochenkov

Institute of Laser and Information Technologies of the Russian Academy of Sciences; 1 Svyatoozerskaya ul., Shatura, Moskovskaya oblast',
140700, Russian Federation
N.N. Blokhin Russian Cancer Research Center; 24 Kashirskoe shosse, Moscow, 115478, Russian Federation

Email: khaydukov@mail.ru
PhD (in Biology), Research Fellow, Laboratory for Nonlinear Optics of Surface and Laser-Plasma Processes, Advanced Laser Technologies Division1 ; Research Fellow, Laboratory of Biomarkers and Mechanisms of Tumor Angiogenesis, Research Institute of Experimental Diagnostics and Tumor Therapy Россия

V. A. Semchishen

Institute of Laser and Information Technologies of the Russian Academy of Sciences; 1 Svyatoozerskaya ul., Shatura, Moskovskaya oblast',
140700, Russian Federation

Email: khaydukov@mail.ru
PhD (in Physics and Mathematics), Leading Research Fellow, Laboratory for Nonlinear Optics of Surface and Laser-Plasma Processes, Advanced Laser Technologies Division Россия

E. V. Khaydukov

Institute of Laser and Information Technologies of the Russian Academy of Sciences; 1 Svyatoozerskaya ul., Shatura, Moskovskaya oblast',
140700, Russian Federation

Author for correspondence.
Email: khaydukov@mail.ru
PhD (in Physics and Mathematics), Senior Research Fellow, Laboratory for Nonlinear Optics of Surface and Laser-Plasma Processes, Advanced Laser Technologies Division Россия

E. V. Stepanova

N.N. Blokhin Russian Cancer Research Center; 24 Kashirskoe shosse, Moscow, 115478, Russian Federation

Email: khaydukov@mail.ru
MD, PhD, Leading Research Fellow, Laboratory of Biomarkers and Mechanisms of Tumor Angiogenesis, Research Institute of Experimental Diagnostics and Tumor Therapy Россия

V. Ya. Panchenko

Institute of Laser and Information Technologies of the Russian Academy of Sciences; 1 Svyatoozerskaya ul., Shatura, Moskovskaya oblast',
140700, Russian Federation

Email: khaydukov@mail.ru
PhD (in Physics and Mathematics), Academician of Russian Academy of Sciences, Professor, Director Россия

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Copyright (c) 2016 Rocheva V.V., Sholina N.V., Derevyashkin S.P., Generalova A.N., Nechaev A.V., Khochenkov D.A., Semchishen V.A., Khaydukov E.V., Stepanova E.V., Panchenko V.Y.

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