biophBiomedical PhotonicsBiomedical Photonics2413-9432Non-profit partnership for development of domestic photodynamic therapy and photodiagnosis10.24931/2413-9432-2018-7-1-4-12bioph-213Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИORIGINAL ARTICLESВИЗУАЛИЗАЦИЯ НАНОЧАСТИЦ LaF3, ДОПИРОВАННЫХ Nd3+, ДЛЯ БИОИМИДЖИНГА В БЛИЖНЕМ ИНФРАКРАСНОМ ДИАПАЗОНЕ ПО АП-КОНВЕРСИОННОЙ ЛЮМИНЕСЦЕНЦИИ ПРИ МИКРОСКОПИИ С МУЛЬТИФОТОННЫМ ВОЗБУЖДЕНИЕМVISUALIZATION OF Nd3+-DOPED LaF3 NANOPARTICLES FOR NEAR INFRARED BIOIMAGING VIA UPCONVERSION LUMINESCENCE AT MULTIPHOTON EXCITATION MICROSCOPYРябоваА. B.RyabovaA. V.nastya.ryabova@gmail.comKeevendK.KeevendK.TsolakiE.TsolakiE.BertazzoS.BertazzoS.ПоминоваД. В.PominovaD. V.РоманишкинИ. Д.RomanishkinI. D.ГрачевП. В.GrachevP. V.МакаровВ. И.MakarovV. I.БурмистровИ. А.BurmistrovI. A.ВанецевА. С.VanetsevA. S.ОрловскаяЕ. О.OrlovskayaE. O.БаранчиковА. Е.BaranchikovA. E.RähnM.RähnM.

Institute of Physics

Institute of Physics

SildosI.SildosI.

Institute of Physics

Institute of Physics

SammelselgV.SammelselgV.

Institute of Physics

Institute of Physics

ЛощеновВ. Б.LoschenovV. B.ОрловскийЮ. В.OrlovskiiY. V.Институт общей физики им. А.М. Прохорова РАНРоссияGeneral Physics Institute of the Russian Academy of SciencesRussian FederationSwiss Federal Laboratories for Materials Science and Technology (Empa)ШвейцарияSwiss Federal Laboratories for Materials Science and Technology (Empa)SwitzerlandUniversity College London (UCL)ВеликобританияUniversity College London (UCL)United KingdomМосковский государственный университет им. М.В. ЛомоносоваРоссияLomonosov Moscow State UniversityRussian FederationИнститут общей физики им. А.М. Прохорова РАН; University of TartuРоссияGeneral Physics Institute of the Russian Academy of Sciences; University of TartuRussian FederationИнститут общей и неорганической химии им. Н.С. Курнакова РАНРоссияKurnakov Institute of General and Inorganic Chemistry RASRussian FederationUniversity of TartuЭстонияUniversity of TartuEstonia20181904201871412Copyright © Рябова А.B., Keevend K., Tsolaki E., Bertazzo S., Поминова Д.В., Романишкин И.Д., Грачев П.В., Макаров В.И., Бурмистров И.А., Ванецев А.С., Орловская Е.О., Баранчиков А.Е., Rähn M., Sildos I., Sammelselg V., Лощенов В.Б., Орловский Ю.В., 20182018Рябова А.B., Keevend K., Tsolaki E., Bertazzo S., Поминова Д.В., Романишкин И.Д., Грачев П.В., Макаров В.И., Бурмистров И.А., Ванецев А.С., Орловская Е.О., Баранчиков А.Е., Rähn M., Sildos I., Sammelselg V., Лощенов В.Б., Орловский Ю.В.Ryabova A.V., Keevend K., Tsolaki E., Bertazzo S., Pominova D.V., Romanishkin I.D., Grachev P.V., Makarov V.I., Burmistrov I.A., Vanetsev A.S., Orlovskaya E.O., Baranchikov A.E., Rähn M., Sildos I., Sammelselg V., Loschenov V.B., Orlovskii Y.V.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.pdt-journal.com/jour/article/view/213

Последние разработки в области биофотоники способствуют повышению интереса к неорганическим наночастицам (НЧ), допированным ионами Nd3+, из-за их поглощения в ближнем инфракрасном (БИК) спектральном диапазоне. Эти НЧ являются перспективными зондами для глубокой визуализации тканей, в то же время они могут служить локальными термометрами в биологических тканях. Несмотря на хорошие возможности визуализации НЧ с ионами Nd3+ в БИК спектральном диапазоне, при изучении внутриклеточного распределения этих НЧ с использованием коммерчески доступных флуоресцентных микроскопических систем возникают трудности из-за ограниченности выбора подходящих детекторов люминесценции. Однако, ионы Nd3+ способны преобразовывать БИК излучение в видимый свет, демонстрируя ап-конверсионные свойства. В этой работе мы определили оптимальные параметры для возбуждения ап-конверсионной люминесценции НЧ Nd3+: LaF в живых клетках и сравнили распределение НЧ внутри клеток культуры человеческих макрофагов THP-1, полученное двумя методами. Во-первых, путем регистрации ап-конверсионной люминесценции НЧ в видимом диапазоне при многофотонном возбуждении в БИК диапазоне спектра с использованием лазерной сканирующей конфокальной микроскопии и, во-вторых, с использованием просвечивающей электронной микроскопии.

Recent developments in the field of biophotonics facilitate the raise of interest to inorganic nanoparticles (NPs) doped with Nd3+ ions, because of their near-infrared (NIR) absorption. These NPs are interesting bioimaging probes for deep tissue visualization, while they can also act as local thermometers in biological tissues. Despite the good possibilities for visualization of NPs with Nd3+ ions in NIR spectral range, difficulties arise when studying the cellular uptake of these NPs using commercially available fluorescence microscopy systems, since the selection of suitable luminescence detectors is limited. However, Nd3+ ions are able to convert NIR radiation into visible light, showing upconversion properties. In this paper we found optimal parameters to excite upconversion luminescence of Nd3++:LaF NPs in living cells and to compare the distribution of the NPs inside the cell culture of human macrophages THP-1 obtained by two methods. Firstly, by detecting the upconversion luminescence of the NPs inVIS under NIR multiphoton excitation using laser scanning confocal microscopy and secondly, using transmission electron microscopy.

наночастицыдопированные Nd3+ближний инфракрасный спектральный диапазонап-конверсионная люминес- ценциямультифотонное возбуждениелазерная сканирующая конфокальная микроскопияNd3+-doped nanoparticlesnear-infraredupconversion luminescencemultiphoton excitationlaser scanning confocal microscopyReferencesEscudero A., Carrillo-Carrión C., Zyuzin M.V., Parak W.J. Luminescent rare-earth-based nanoparticles: a summarized overview of their synthesis, functionalization, and applications // Top Curr Chem (Cham). – 2016. – Vol. 374(4). – P. 48. https://doi.org/10.1007/s41061-016-0049-8.Escudero A., Carrillo-Carrión C., Zyuzin M.V., Parak W.J. Luminescent rare-earth-based nanoparticles: a summarized overview of their synthesis, functionalization, and applications, Top Curr Chem (Cham), 2016, Vol. 374(4), p. 48. Available at: https://doi.org/10.1007/s41061-016-0049-8Ma D., Xu X., Hu M., et al. Rare-earth-based nanoparticles with simultaneously enhanced near-infrared (NIR)-visible (Vis) and NIR-NIR dual-conversion luminescence for multimodal imaging // Chem Asian J. – 2016. – Vol. 11(7). – P. 1050-1058. http://dx.doi.org/10.1002/asia.201501456.Ma D., Xu X., Hu M., Wang J., Zhang Z., Yang J., Meng L. Rare-earthbased nanoparticles with simultaneously enhanced near-infrared (NIR)-visible (Vis) and NIR-NIR dual-conversion luminescence for multimodal imaging, Chem Asian J, 2016, Vol. 11(7), pp. 1050-1058. Available at: http://dx.doi.org/10.1002/asia.201501456Li X., Wang R., Zhang F., et al. Nd3+ Sensitized up/down converting dual-mode nanomaterials for efficient in-vitro and in-vivo bioimaging excited at 800 nm // Sci. Rep. – 2013. – Vol. 3. – P. 3536. http://dx.doi.org/10.1038/srep03536.Li X., Wang R., Zhang F., Zhou L., Shen D., Yao C., Zhao D. Nd3+ Sensitized up/down converting dual-mode nanomaterials for efficient in-vitro and in-vivo bioimaging excited at 800 nm, Sci. Rep., 2013, Vol. 3, p. 3536. Available at: http://dx.doi.org/10.1038/srep03536Wang Z., Zhang P., Yuan Q., et al. Nd³+-sensitized NaLuF₄ luminescent nanoparticles for multimodal imaging and temperature sensing under 808 nm excitation // Nanoscale. – 2015. – Vol. 7(42). – P. 17861-17870. http://dx.doi.org/10.1039/C5NR04889C.Wang Z., Zhang P., Yuan Q., Xu X., Lei P., Liu X., Su Y., Dong L., Feng J., Zhang H. Nd³+-sensitized NaLuF₄ luminescent nanoparticles for multimodal imaging and temperature sensing under 808 nm excitation, Nanoscale, 2015, Vol. 7(42), pp. 17861-17870. Available at: http://dx.doi.org/10.1039/C5NR04889CZhong Y., Tian G., Gu Z., et al. Elimination of photon quenching by a transition layer to fabricate a quenching-shield sandwich structure for 800 nm excited upconversion luminescence of Nd3+-sensitized nanoparticles // Adv. Mater. – 2014. – Vol. 26(18). – P. 2831-2837. http://dx.doi.org/10.1002/ adma.201304903.Zhong Y., Tian G., Gu Z., Yang Y., Gu L., Zhao Y., Ma Y., Yao J. Elimination of photon quenching by a transition layer to fabricate a quenching-shield sandwich structure for 800 nm excited upconversion luminescence of Nd3+-sensitized nanoparticles, Adv. Mater., 2014, Vol. 26(18), pp. 2831-2837. Available at: http://dx.doi.org/10.1002/adma.201304903Zhan Q., Wang B., Wen X., He S. Controlling the excitation of upconverting luminescence for biomedical theranostics: neodymium sensitizing // Opt. Mater. Express. – 2016. – Vol. 6. – P. 1011-1023. https://doi.org/10.1364/OME.6.001011.Zhan Q., Wang B., Wen X., He S. Controlling the excitation of upconverting luminescence for biomedical theranostics: neodymium sensitizing, Opt. Mater. Express, 2016, Vol. 6, pp. 1011-1023. Available at: https://doi.org/10.1364/OME.6.001011Kushida T., Marcos H.M., Geusic J.E. Laser transition cross section and fluorescence branching ratio for Nd3+ in yttrium aluminum garnet // Phys. Rev. – 1968. – Vol. 167. – P. 289-291. https://doi.org/10.1103/PhysRev.167.289.Kushida T., Marcos H.M., Geusic J.E. Laser transition cross section and fluorescence branching ratio for Nd3+ in yttrium aluminum garnet, Phys. Rev., 1968, Vol. 167, pp. 289-291. Available at: https://doi.org/10.1103/PhysRev.167.289Xu B., Zhang X., Huang W., et al. Nd3+ sensitized dumbbell-like upconversion nanoparticles for photodynamic therapy application // J. Mater. Chem. B. – 2016. – Vol. 4. – P. 2776-2784. http://dx.doi.org/10.1039/C6TB00542J.Xu B., Zhang X., Huang W., Yang Y., Ma Y., Gu Z., Zhai T., Zhao Y. Nd3+ sensitized dumbbell-like upconversion nanoparticles for photodynamic therapy application, J. Mater. Chem. B., 2016, Vol. 4, pp. 27762784. Available at: http://dx.doi.org/10.1039/C6TB00542JWang Y.F., Liu G.Y., Sun L.D., et al. Nd(3+)-sensitized upconversion nanophosphors: efficient in vivo bioimaging probes with minimized heating effect // ACS Nano. – 2013. – Vol. 7. – P. 7200-7206. doi:10.1021/nn402601d.Wang Y.F., Liu G.Y., Sun L.D., Xiao J.W., Zhou J.C., Yan C.H. Nd(3+)sensitized upconversion nanophosphors: efficient in vivo bioimaging probes with minimized heating effect, ACS Nano, 2013, Vol. 7, pp. 7200-7206. doi:10.1021/nn402601dQin Q.-S., Zhang P.-Z., Sun L.-D., et al. Ultralow-power near-infrared excited neodymium-doped nanoparticles for long-term in vivo bioimaging // Nanoscale. – 2017. – Vol. 9. – P. 4660-4664. http://dx.doi.org/10.1039/C7NR00606C.Qin Q.-S., Zhang P.-Z., Sun L.-D., Shi S., Chen N.-X., Dong H., Zheng X.-Y., Li L.-M. and Yan C.-H. Ultralow-power near-infrared excited neodymium-doped nanoparticles for long-term in vivo bioimaging, Nanoscale, 2017, Vol. 9, pp. 4660-4664. Available at: http://dx.doi.org/10.1039/C7NR00606CRocha U., Hu J., Rodriguez E.M., Vanetsev A.S., Rähn M., Sammelselg V., Orlovskii Y.V., García Sole J., Jaque D., Ortgies D.H. Subtissue Imaging and Thermal Monitoring of Gold Nanorods through Joined Encapsulation with Nd-Doped Infrared-Emitting Nanoparticles, Small, 2016, Vol. 12, pp. 5394-5400. Available at: http://dx.doi.org/10.1002/smll.201600866Rocha U., Hu J., Rodriguez E.M., Vanetsev A.S., Rähn M., Sammelselg V., Orlovskii Y.V., García Sole J., Jaque D., Ortgies D.H. Subtissue Imaging and Thermal Monitoring of Gold Nanorods through Joined Encapsulation with Nd-Doped Infrared-Emitting Nanoparticles, Small, 2016, Vol. 12, pp. 5394-5400. Available at: http://dx.doi.org/10.1002/smll.201600866Pichaandi J., Boyer J.-C., Delaney K.R., van Veggel F.C.J.M. Two-pho-evaluation of their performance and potential in bioimaging // J. Phys. Chem. C. – 2011. – Vol. 115. – P. 19054-19064. doi:10.1021/jp206345j.Pichaandi J., Boyer J.-C., Delaney K.R., van Veggel F.C.J.M. Two-photon upconversion laser (scanning and wide-field) microscopy using Ln3+-doped NaYF4 upconverting nanocrystals: a critical evaluation of their performance and potential in bioimaging, J. Phys. Chem. C., 2011, Vol. 115, pp. 19054-19064. doi:10.1021/jp206345jZhan Q., He S., Qian J., et al. Optimization of optical excitation of upconversion nanoparticles for rapid microscopy and deeper tissue imaging with higher quantum yield // Theranostics. – 2013. – Vol. 3. – P. 306-316. doi:10.7150/thno.6007.Zhan Q., He S., Qian J., Cheng H., Cai F. Optimization of optical excitation of upconversion nanoparticles for rapid microscopy and deeper tissue imaging with higher quantum yield, Theranostics, 2013, Vol. 3, pp. 306-316. doi:10.7150/thno.6007Wu R., Zhan Q., Liu H., et al. Optical depletion mechanism of upconverting luminescence and its potential for multi-photon STED-like microscopy // Opt. Express. – 2015. – Vol. 23. – P. 32401-32412. https://doi.org/10.1364/OE.23.032401.Wu R., Zhan Q., Liu H., Wen X., Wang B., He S. Optical depletion mechanism of upconverting luminescence and its potential for multi-photon STED-like microscopy, Opt. Express, 2015, Vol. 23, pp. 32401-32412. Available at: https://doi.org/10.1364/OE.23.032401Wang B., Zhan Q., Zhao Y., et al. Visible-to-visible fourphoton ultrahigh resolution microscopic imaging with 730-nm diode laser excited nanocrystals // Opt. Express.– 2016. – Vol. 24(2). – A302-A311. https://doi.org/10.1364/OE.24.00A302.Wang B., Zhan Q., Zhao Y., Wu R., Liu J., He S. Visible-to-visible fourphoton ultrahigh resolution microscopic imaging with 730-nm diode laser excited nanocrystals, Opt. Express, 2016, Vol. 24(2), pp. A302-A311. Available at: https://doi.org/10.1364/OE.24.00A302Vanetsev A., Kaldvee K., Puust L., et al. Relation of crystallinity and fluorescent properties of LaF3:Nd3+ nanoparticles synthesized with different water-based techniques. // Chemistry Select. – 2017. – Vol. 2. – P. 4874-4881. http://dx.doi.org/10.1002/slct.201701075.Vanetsev A., Kaldvee K., Puust L., et al. Relation of crystallinton upconversion laser (scanning and wide-field) microscopy using Ln3+-doped NaYF4 upconverting nanocrystals: a critical evaluation of their performance and potential in bioimaging, J. Phys. Chem. C., 2011, Vol. 115, pp. 19054-19064. doi:10.1021/jp206345jShcherbakov A.B., Zholobak N.M., Baranchikov A.E., et al. Cerium fluoride nanoparticles protect cells against oxidative stress // Mater Sci. Eng. C Mater Biol. Appl. – 2015. – Vol. 50. – P. 151-159. https://doi.org/10.1016/j.msec.2015.01.094.Shcherbakov A.B., Zholobak N.M., Baranchikov A.E., Ryabova A.V., Ivanov V.K. Cerium fluoride nanoparticles protect cells against oxidative stress, Mater Sci. Eng. C Mater Biol. Appl., 2015, Vol. 50, pp. 151-159. Available at: https://doi.org/10.1016/j.msec.2015.01.094Carnall W.T., Crosswhite Hannah, Crosswhite H.M. Energy level structure and transition probabilities in the spectra of the trivalent lanthanides in LaF3. – United States, 1978. doi:10.2172/6417825.Carnall W.T., Crosswhite Hannah, Crosswhite H.M. Energy level structure and transition probabilities in the spectra of the trivalent lanthanides in LaF3. United States, 1978. doi:10.2172/6417825Carnall W.T., Goodman G.L., Rajnak K., Rana R.S. A systematic analysis of the spectra of the lanthanides doped into single crystal LaF3 // J. Chem. Phys. – 1989. – Vol. 90. – P. 3443. http://dx.doi.org/10.1063/1.455853.Carnall W.T., Goodman G.L., Rajnak K., Rana R.S. A systematic analysis of the spectra of the lanthanides doped into single crystal LaF3, Chem. Phys., 1989, Vol. 90, p. 3443. Available at: http://dx.doi.org/10.1063/1.455853Pollnau M., Gamelin D.R., Luthi S.R., et al. Power dependence of upconversion luminescence in lanthanide and transition-metalion systems // Phys. Rev. B. – 2000. – Vol. 61. – P. 3337-3346. https://doi.org/10.1103/PhysRevB.61.3337.Pollnau M., Gamelin D.R., Luthi S.R., Gudel H.U., Hehlen M.P. Power dependence of upconversion luminescence in lanthanide and transition-metal-ion systems, Phys. Rev. B., 2000, Vol. 61, pp. 33373346. Available at: https://doi.org/10.1103/PhysRevB.61.3337Jacinto C., Oliveira S.L., Catunda T., et al. Upconversion effect on fluorescence quantum efficiency and heat generation in Nd3+-doped materials // Opt. Express. – 2005. – Vol. 13. – P. 2040-2046. https://doi.org/10.1364/OPEX.13.002040.Jacinto C., Oliveira S.L., Catunda T., Andrade A.A., Myers J.D., Myers M.J. Upconversion effect on fluorescence quantum efficiency and heat generation in Nd3+-doped materials, Opt. Express, 2005, Vol. 13, pp. 2040-2046. Available at: https://doi.org/10.1364/OPEX.13.002040Fröhlich E. The role of surface charge in cellular uptake and cytotoxicity of medical nanoparticles // Int. J. Nanomedicine. – 2012. – Vol. 7. – P. 5577-5591. https://doi.org/10.2147/IJN.S36111.Fröhlich E. The role of surface charge in cellular uptake and cytotoxicity of medical nanoparticles, Int. J. Nanomedicine, 2012, Vol. 7, pp. 5577-5591. Available at: https://doi.org/10.2147/IJN.S36111Sojka B., Liskova A., Kuricova M., et al. The effect of core and lanthanide ion dopants in sodium fluoride-based nanocrystals on phagocytic activity of human blood leukocytes // J. Nanopart. Res. – 2017. – Vol. 19. – P. 68. https://doi.org/10.1007/s11051-0173779-9.Sojka B., Liskova A., Kuricova M., Banski M., Misiewicz J., Dusinska M., Horvathova M., IlavskaS., Szabova M., Rollerova E., Podhorodecki A., Tulinska J. The effect of core and lanthanide ion dopants in sodium fluoride-based nanocrystals on phagocytic activity of human blood leukocytes, J. Nanopart. Res., 2017, Vol. 19, p. 68. Available at: https://doi.org/10.1007/s11051-017-3779-9

The authors declare that there are no conflicts of interest present.