Login | Register

A Lanthanide-Doped Nanoparticle System for Dual Photodynamic Therapy of Lung Cancer


A Lanthanide-Doped Nanoparticle System for Dual Photodynamic Therapy of Lung Cancer

Vettier, Freesia (2023) A Lanthanide-Doped Nanoparticle System for Dual Photodynamic Therapy of Lung Cancer. Masters thesis, Concordia University.

[thumbnail of Vettier_Msc_W2023.pdf]
Text (application/pdf)
Vettier_Msc_W2023.pdf - Accepted Version
Restricted to Repository staff only until 1 March 2024.
Available under License Spectrum Terms of Access.


Lanthanide-doped nanoparticles (NPs) have been used to improve photodynamic therapy (PDT) through modulation of the excitation wavelength using near-infrared (NIR) light or X-rays to achieve upconversion or radioluminescence, respectively. We developed a NP that can undergo both mechanisms to excite a powerful photosensitizer, Rose Bengal (RB), when simultaneously irradiated with NIR and X-rays. A range of ion concentrations were investigated leading to the development of the optimal composition: NaLuF4: 20% Gd3+, 1% Dy3+, 1% Yb3+, 0.001% Er3+. The mechanisms of ion interactions were investigated along with their luminescence properties under both modes of excitation. RB was loaded into a mesoporous silica shell coating the NPs, and studies were completed in vitro to determine the outcome of the treatment on A549 cells. Viability assays, clonogenic assays, and microscopy were used to investigate this system under various conditions and irradiation combinations. Herein, we demonstrate that the NPs without RB act as radiosensitizers when excited with X-rays, enhancing the treatment via a dose enhancement effect. When RB-loaded NPs are excited with NIR and X-rays simultaneously, the dual Photodynamic therapy (PDT) treatment showed the greatest treatment outcome when compared to upconversion PDT and X-ray mediated PDT (X-PDT) individually. This work is a proof of concept that suggests that a dual PDT nanoparticle system could improve the outlook for lung cancer patients in the future.

Divisions:Concordia University > Faculty of Arts and Science > Chemistry and Biochemistry
Item Type:Thesis (Masters)
Authors:Vettier, Freesia
Institution:Concordia University
Degree Name:M. Sc.
Date:6 March 2023
Thesis Supervisor(s):Capobianco, John
Keywords:photodynamic therapy, Lanthanide-doped nanoparticles, lung cancer, Non-small cell lung cancer, X-ray mediated photodynamic therapy, Upconversion, Radioluminescence, Upconversion photodynamic therapy
ID Code:991898
Deposited By: Freesia Vettier
Deposited On:21 Jun 2023 14:54
Last Modified:21 Jun 2023 14:54


Bray, F.; Ferlay, J.; Soerjomataram, I.; Siegel, R. L.; Torre, L. A.; Jemal, A. Global Cancer Statistics 2018: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA. Cancer J. Clin. 2018, 68 (6), 394–424. https://doi.org/10.3322/caac.21492.
(2) Canadian Cancer Statistics. Cancer Statistics at a Glance - Canadian Cancer Society. Can. Cancer Soc. 2016, No. January 2018, 4–7.
(3) PDQ Adult Treatment Editorial Board. Non-Small Cell Lung Cancer Treatment (PDQ®): Patient Version; 2002.
(4) PDQ Adult Treatment Editorial Board. Small Cell Lung Cancer Treatment (PDQ®): Patient Version. PDQ Cancer Inf. Summ. 2002.
(5) Yamaoka, T. Understanding the EGFR Mutation Aids the Fight against Lung Cancer. Res. Outreach 2020, No. 114, 50–53. https://doi.org/10.32907/RO-114-5053.
(6) Park, K. S.; Liang, M. C.; Raiser, D. M.; Zamponi, R.; Roach, R. R.; Curtis, S. J.; Walton, Z.; Schaffer, B. E.; Roake, C. M.; Zmoos, A. F.; Kriegel, C.; Wong, K. K.; Sage, J.; Kim, C. F. Characterization of the Cell of Origin for Small Cell Lung Cancer. Cell Cycle 2011, 10 (16), 2806–2815. https://doi.org/10.4161/cc.10.16.17012.
(7) Healthline. Types of Non-Small Cell Lung Cancer: Causes, Treatment, and Outlook https://www.healthline.com/health/lung-cancer/types-of-non-small-cell-lung-cancer#types (accessed Feb 5, 2023).
(8) Dela Cruz, C. S.; Tanoue, L. T.; Matthay, R. A. Lung Cancer: Epidemiology, Etiology, and Prevention. Clinics in Chest Medicine. December 2011, pp 605–644. https://doi.org/10.1016/j.ccm.2011.09.001.
(9) Rami-Porta, R.; Goldstraw, P.; Pass, H. I. The Eighth Edition of the Tumor, Node, and Metastasis Classification of Lung Cancer. In IASLC Thoracic Oncology; Elsevier, 2018; pp 253-264.e1. https://doi.org/10.1016/B978-0-323-52357-8.00025-1.
(10) Giard, D. J.; Aaronson, S. A.; Todaro, G. J.; Arnstein, P.; Kersey, J. H.; Dosik, H.; Parks, W. P. In Vitro Cultivation of Human Tumors: Establishment of Cell Lines Derived from a Series of Solid Tumors. J. Natl. Cancer Inst. 1973, 51 (5), 1417–1423.
(11) Franklin, M. A549 - A Model for Non-Small Cell Lung Cancer - MI Bioresearch. MI Bioresearch Inc 2016, No. 734, 1–7.
(12) Korrodi-Gregório, L.; Soto-Cerrato, V.; Vitorino, R.; Fardilha, M.; Pérez-Tomás, R. From Proteomic Analysis to Potential Therapeutic Targets: Functional Profile of Two Lung Cancer Cell Lines, A549 and SW900, Widely Studied in Pre-Clinical Research. PLoS One 2016, 11 (11), e0165973. https://doi.org/10.1371/journal.pone.0165973.
(13) www.atcc.org. A549 - CCL-185 | ATCC https://www.atcc.org/products/ccl-185 (accessed Feb 22, 2023).
(14) Ellis, P. M.; Vandermeer, R. Delays in the Diagnosis of Lung Cancer. J. Thorac. Dis. 2011, 3 (3), 183–188. https://doi.org/10.3978/j.issn.2072-1439.2011.01.01.
(15) Ay Eren, A.; Eren, M. F.; Koca, S. The Effect of Thoracic Radiotherapy on the Quality of Life in Lung Cancer Patients. Cureus 2021, 13 (3), e13870. https://doi.org/10.7759/cureus.13870.
(16) Bouleftour, W.; Rowinski, E.; Louati, S.; Sotton, S.; Wozny, A.-S.; Moreno-Acosta, P.; Mery, B.; Rodriguez-Lafrasse, C.; Magne, N. A Review of the Role of Hypoxia in Radioresistance in Cancer Therapy. Med. Sci. Monit. 2021, 27, 1–7. https://doi.org/10.12659/MSM.934116.
(17) Castedo, M.; Perfettini, J. L.; Roumier, T.; Andreau, K.; Medema, R.; Kroemer, G. Cell Death by Mitotic Catastrophe: A Molecular Definition. Oncogene. 2004, pp 2825–2837. https://doi.org/10.1038/sj.onc.1207528.
(18) Kepka, L.; Socha, J. Dose and Fractionation Schedules in Radiotherapy for Non-Small Cell Lung Cancer. Transl. Lung Cancer Res. 2021, 10 (4), 1969–1982. https://doi.org/10.21037/tlcr-20-253.
(19) Chan, C.; Lang, S.; Rowbottom, C.; Guckenberger, M.; Faivre-Finn, C. Intensity-Modulated Radiotherapy for Lung Cancer: Current Status and Future Developments. J. Thorac. Oncol. 2014, 9 (11), 1598–1608. https://doi.org/10.1097/JTO.0000000000000346.
(20) Sebastian, N. T.; Xu-Welliver, M.; Williams, T. M. Stereotactic Body Radiation Therapy
(SBRT) for Early Stage Non-Small Cell Lung Cancer (NSCLC): Contemporary Insights and Advances. J. Thorac. Dis. 2018, 10 (S21), S2451–S2464. https://doi.org/10.21037/jtd.2018.04.52.
(21) Parashar, B.; Arora, S.; Wernicke, A. Radiation Therapy for Early Stage Lung Cancer. Semin. Intervent. Radiol. 2013, 30 (02), 185–190. https://doi.org/10.1055/s-0033-1342960.
(22) Césaire, M.; Montanari, J.; Curcio, H.; Lerouge, D.; Gervais, R.; Demontrond, P.; Balosso, J.; Chevalier, F. Radioresistance of Non-Small Cell Lung Cancers and Therapeutic Perspectives. Cancers (Basel). 2022, 14 (12), 2829. https://doi.org/10.3390/cancers14122829.
(23) Maréchal, A.; Zou, L. DNA Damage Sensing by the ATM and ATR Kinases. Cold Spring Harb. Perspect. Biol. 2013, 5 (9), 1–18. https://doi.org/10.1101/cshperspect.a012716.
(24) Chatterjee, N.; Walker, G. C. Mechanisms of DNA Damage, Repair, and Mutagenesis. Environ. Mol. Mutagen. 2017, 58 (5), 235–263. https://doi.org/10.1002/em.22087.
(25) Huang, R. X.; Zhou, P. K. DNA Damage Response Signaling Pathways and Targets for Radiotherapy Sensitization in Cancer. Signal Transduct. Target. Ther. 2020, 5 (1). https://doi.org/10.1038/s41392-020-0150-x.
(26) Binkley, M. S.; Jeon, Y.-J.; Nesselbush, M.; Moding, E. J.; Nabet, B. Y.; Almanza, D.; Kunder, C.; Stehr, H.; Yoo, C. H.; Rhee, S.; Xiang, M.; Chabon, J. J.; Hamilton, E.; Kurtz, D. M.; Gojenola, L.; Owen, S. G.; Ko, R. B.; Shin, J. H.; Maxim, P. G.; Lui, N. S.; Backhus, L. M.; Berry, M. F.; Shrager, J. B.; Ramchandran, K. J.; Padda, S. K.; Das, M.; Neal, J. W.; Wakelee, H. A.; Alizadeh, A. A.; Loo, B. W.; Diehn, M. KEAP1/NFE2L2 Mutations Predict Lung Cancer Radiation Resistance That Can Be Targeted by Glutaminase Inhibition. Cancer Discov. 2020, 10 (12), 1826–1841. https://doi.org/10.1158/2159-8290.CD-20-0282.
(27) Cancer research UK. Side Effects of Lung Cancer Radiotherapy | Cancer Research UK. 2016.
(28) Liu, Y.; Zhang, P.; Li, F.; Jin, X.; Li, J.; Chen, W.; Li, Q. Metal-Based NanoEnhancers for Future Radiotherapy: Radiosensitizing and Synergistic Effects on Tumor Cells. Theranostics 2018, 8 (7), 1824–1849. https://doi.org/10.7150/thno.22172.
(29) Gong, L.; Zhang, Y.; Liu, C.; Zhang, M.; Han, S. Application of Radiosensitizers in Cancer Radiotherapy. International Journal of Nanomedicine. 2021, pp 1083–1102. https://doi.org/10.2147/IJN.S290438.
(30) Gong, L.; Zhang, Y.; Liu, C.; Zhang, M.; Han, S. Application of Radiosensitizers in Cancer Radiotherapy. International Journal of Nanomedicine. Dove Press 2021, pp 1083–1102. https://doi.org/10.2147/IJN.S290438.
(31) Klein, J. S.; Sun, C.; Pratx, G. Radioluminescence in Biomedicine: Physics, Applications, and Models. Phys. Med. Biol. 2019, 64 (4), 04TR01. https://doi.org/10.1088/1361-6560/aaf4de.
(32) Verry, C.; Dufort, S.; Villa, J.; Gavard, M.; Iriart, C.; Grand, S.; Charles, J.; Chovelon, B.; Cracowski, J.-L.; Quesada, J.-L.; Mendoza, C.; Sancey, L.; Lehmann, A.; Jover, F.; Giraud, J.-Y.; Lux, F.; Crémillieux, Y.; McMahon, S.; Pauwels, P. J.; Cagney, D.; Berbeco, R.; Aizer, A.; Deutsch, E.; Loeffler, M.; Le Duc, G.; Tillement, O.; Balosso, J. Theranostic AGuIX Nanoparticles as Radiosensitizer: A Phase I, Dose-Escalation Study in Patients with Multiple Brain Metastases (NANO-RAD Trial). Radiother. Oncol. 2021, 160, 159–165. https://doi.org/10.1016/j.radonc.2021.04.021.
(33) Leeman, J. Nano-SMART: nanoparticles With MR Guided SBRT in NSCLC and Pancreatic Cancer https://clinicaltrials.gov/ct2/show/NCT04789486?term=AGuIX&draw=2&rank=6 (accessed Feb 23, 2023).
(34) Baptista, M. S.; Cadet, J.; Di Mascio, P.; Ghogare, A. A.; Greer, A.; Hamblin, M. R.; Lorente, C.; Nunez, S. C.; Ribeiro, M. S.; Thomas, A. H.; Vignoni, M.; Yoshimura, T. M. Type I and Type II Photosensitized Oxidation Reactions: Guidelines and Mechanistic Pathways. Photochemistry and Photobiology. John Wiley & Sons, Ltd July 1, 2017, pp 912–919. https://doi.org/10.1111/php.12716.
(35) Abrahamse, H.; Hamblin, M. R. New Photosensitizers for Photodynamic Therapy. Biochem. J. 2016, 473 (4), 347–364. https://doi.org/10.1042/BJ20150942.
(36) Nsubuga, A.; Mandl, G. A.; Capobianco, J. A. Investigating the Reactive Oxygen Species Production of Rose Bengal and Merocyanine 540-Loaded Radioluminescent Nanoparticles.
Nanoscale Adv. 2021, 3 (5), 1375–1381. https://doi.org/10.1039/d0na00964d.
(37) Dayem, A. A.; Hossain, M. K.; Lee, S. Bin; Kim, K.; Saha, S. K.; Yang, G. M.; Choi, H. Y.; Cho, S. G. The Role of Reactive Oxygen Species (ROS) in the Biological Activities of Metallic Nanoparticles. International Journal of Molecular Sciences. MDPI AG January 10, 2017. https://doi.org/10.3390/ijms18010120.
(38) SPILLER, W.; KLIESCH, H.; WÖHRLE, D.; HACKBARTH, S.; RÖDER, B.; SCHNURPFEIL, G. Singlet Oxygen Quantum Yields of Different Photosensitizers in Polar Solvents and Micellar Solutions. J. Porphyr. Phthalocyanines 1998, 02 (02), 145–158. https://doi.org/10.1002/(SICI)1099-1409(199803/04)2:2<145::AID-JPP60>3.0.CO;2-2.
(39) Quina, F. H.; Silva, G. T. M. The Photophysics of Photosensitization: A Brief Overview. J. Photochem. Photobiol. 2021, 7 (April), 100042. https://doi.org/10.1016/j.jpap.2021.100042.
(40) Lambert, C. R.; Kochevar, I. E. Electron Transfer Quenching of the Rose Bengal Triplet State. Photochem. Photobiol. 1997, 66 (1), 15–25. https://doi.org/10.1111/j.1751-1097.1997.tb03133.x.
(41) Vanerio, N.; Stijnen, M.; de Mol, B. A. J. M.; Kock, L. M. Biomedical Applications of Photo- and Sono-Activated Rose Bengal: A Review. Photobiomodulation, Photomedicine, Laser Surg. 2019, 37 (7), 383–394. https://doi.org/10.1089/photob.2018.4604.
(42) Simone, C. B.; Friedberg, J. S.; Glatstein, E.; Stevenson, J. P.; Sterman, D. H.; Hahn, S. M.; Cengel, K. A. Photodynamic Therapy for the Treatment of Non-Small Cell Lung Cancer. J. Thorac. Dis. 2012, 4 (1), 63–75. https://doi.org/10.3978/ j.issn.2072-1439.2011.11.05.
(43) Correia, J. H.; Rodrigues, J. A.; Pimenta, S.; Dong, T.; Yang, Z. Photodynamic Therapy Review: Principles, Photosensitizers, Applications, and Future Directions. Pharmaceutics 2021, 13 (9), 1332. https://doi.org/10.3390/pharmaceutics13091332.
(44) Collins, S. R. Elsevier’s 2022 Intravenous Medications - E-Book: A Handbook for Nurses and Health Professionals; Elsevier Health Sciences, 2021.
(45) Ruggiero, E.; Alonso-De Castro, S.; Habtemariam, A.; Salassa, L. Upconverting Nanoparticles for the near Infrared Photoactivation of Transition Metal Complexes: New Opportunities and Challenges in Medicinal Inorganic Photochemistry. Dalt. Trans. 2016,
45 (33), 13012–13020. https://doi.org/10.1039/c6dt01428c.
(46) Borgia, F.; Giuffrida, R.; Caradonna, E.; Vaccaro, M.; Guarneri, F.; Cannavò, S. Early and Late Onset Side Effects of Photodynamic Therapy. Biomedicines 2018, 6 (1), 12. https://doi.org/10.3390/biomedicines6010012.
(47) Dhaini, B.; Wagner, L.; Moinard, M.; Daouk, J.; Arnoux, P.; Schohn, H.; Schneller, P.; Acherar, S.; Hamieh, T.; Frochot, C. Importance of Rose Bengal Loaded with Nanoparticles for Anti-Cancer Photodynamic Therapy. Pharmaceuticals 2022, 15 (9). https://doi.org/10.3390/ph15091093.
(48) Yi, G.; Hong, S. H.; Son, J.; Yoo, J.; Park, C.; Choi, Y.; Koo, H. Recent Advances in Nanoparticle Carriers for Photodynamic Therapy. Quant. Imaging Med. Surg. 2018, 8 (4), 433–443. https://doi.org/10.21037/qims.2018.05.04.
(49) Lucky, S. S.; Soo, K. C.; Zhang, Y. Nanoparticles in Photodynamic Therapy. Chem. Rev. 2015, 115 (4), 1990–2042. https://doi.org/10.1021/cr5004198.
(50) Larue, L.; Ben Mihoub, A.; Youssef, Z.; Colombeau, L.; Acherar, S.; André, J. C.; Arnoux, P.; Baros, F.; Vermandel, M.; Frochot, C. Using X-Rays in Photodynamic Therapy: An Overview. Photochem. Photobiol. Sci. 2018, 17 (11), 1612–1650. https://doi.org/10.1039/c8pp00112j.
(51) Kwiatkowski, S.; Knap, B.; Przystupski, D.; Saczko, J.; Kędzierska, E.; Knap-Czop, K.; Kotlińska, J.; Michel, O.; Kotowski, K.; Kulbacka, J. Photodynamic Therapy – Mechanisms, Photosensitizers and Combinations. Biomedicine and Pharmacotherapy. Elsevier Masson October 1, 2018, pp 1098–1107. https://doi.org/10.1016/j.biopha.2018.07.049.
(52) Sabri, T.; Pawelek, P. D.; Capobianco, J. A. Dual Activity of Rose Bengal Functionalized to Albumin-Coated Lanthanide-Doped Upconverting Nanoparticles: Targeting and Photodynamic Therapy. ACS Appl. Mater. Interfaces 2018, 10 (32), 26947–26953. https://doi.org/10.1021/acsami.8b08919.
(53) Bünzli, J. C. G. Lanthanide Luminescence for Biomedical Analyses and Imaging. Chem. Rev. 2010, 110 (5), 2729–2755. https://doi.org/10.1021/cr900362e.
(54) Wells, W. H.; Wells, V. L. The Lanthanides, Rare Earth Elements. In Patty’s Toxicology;
John Wiley & Sons, Inc.: Hoboken, NJ, USA, 2012; pp 817–840. https://doi.org/10.1002/0471435139.tox043.pub2.
(55) Bünzli, J.-C. G.; Eliseeva, S. V. Basics of Lanthanide Photophysics. In Springer Series on Fluorescence, Vol. 7; 2010; Vol. 7, pp 1–45. https://doi.org/10.1007/4243_2010_3.
(56) Zhou, M.; Li, Y.; Chang, Q.; Sun, Q.; Su, Q. Upconversion Nanoparticles for the Future of Biosensing. In Sensing and Biosensing with Optically Active Nanomaterials; Elsevier, 2021; pp 305–363. https://doi.org/10.1016/B978-0-323-90244-1.00002-1.
(57) Maurizio, S. L.; Mandl, G. A.; Long, M. D.; Capobianco, J. A. Investigating the Fundamental Material Properties That Influence the Radioluminescence of Lanthanide-Doped Nanoparticles. Chem. Mater. 2022, 34 (22), 10123–10132. https://doi.org/10.1021/acs.chemmater.2c02830.
(58) Kaur, M.; Mandl, G. A.; Maurizio, S. L.; Tessitore, G.; Capobianco, J. A. On the Photostability and Luminescence of Dye-Sensitized Upconverting Nanoparticles Using Modified IR820 Dyes. Nanoscale Adv. 2022, 4 (2), 608–618. https://doi.org/10.1039/d1na00710f.
(59) Cooper, D. R.; Capobianco, J. A.; Seuntjens, J. Radioluminescence Studies of Colloidal Oleate-Capped β-Na(Gd,Lu)F4:Ln3+ Nanoparticles (Ln = Ce, Eu, Tb). Nanoscale 2018, 10 (16), 7821–7832. https://doi.org/10.1039/c8nr01262h.
(60) Ahmad, F.; Wang, X.; Jiang, Z.; Yu, X.; Liu, X.; Mao, R.; Chen, X.; Li, W. Codoping Enhanced Radioluminescence of Nanoscintillators for X-Ray-Activated Synergistic Cancer Therapy and Prognosis Using Metabolomics. ACS Nano 2019, 13 (9), 10419–10433. https://doi.org/10.1021/acsnano.9b04213.
(61) Wang, G. D.; Nguyen, H. T.; Chen, H.; Cox, P. B.; Wang, L.; Nagata, K.; Hao, Z.; Wang, A.; Li, Z.; Xie, J. X-Ray Induced Photodynamic Therapy: A Combination of Radiotherapy and Photodynamic Therapy. Theranostics 2016, 6 (13), 2295–2305. https://doi.org/10.7150/thno.16141.
(62) Auzel, F. Upconversion and Anti-Stokes Processes with f and d Ions in Solids. Chemical Reviews. American Chemical Society January 2004, pp 139–173. https://doi.org/10.1021/cr020357g.
(63) Dong, H.; Sun, L. D.; Yan, C. H. Energy Transfer in Lanthanide Upconversion Studies for Extended Optical Applications. Chemical Society Reviews. The Royal Society of Chemistry March 10, 2015, pp 1608–1634. https://doi.org/10.1039/c4cs00188e.
(64) Wang, X.; Valiev, R. R.; Ohulchanskyy, T. Y.; Ågren, H.; Yang, C.; Chen, G. Dye-Sensitized Lanthanide-Doped Upconversion Nanoparticles. Chemical Society Reviews. The Royal Society of Chemistry July 17, 2017, pp 4150–4167. https://doi.org/10.1039/c7cs00053g.
(65) Wisser, M. D.; Fischer, S.; Siefe, C.; Alivisatos, A. P.; Salleo, A.; Dionne, J. A. Improving Quantum Yield of Upconverting Nanoparticles in Aqueous Media via Emission Sensitization. Nano Lett. 2018, 18 (4), 2689–2695. https://doi.org/10.1021/acs.nanolett.8b00634.
(66) Castano, A. P.; Demidova, T. N.; Hamblin, M. R. Mechanisms in Photodynamic Therapy: Part One—Photosensitizers, Photochemistry and Cellular Localization. Photodiagnosis Photodyn. Ther. 2004, 1 (4), 279–293. https://doi.org/10.1016/S1572-1000(05)00007-4.
(67) Wang, C.; Cheng, L.; Liu, Z. Upconversion Nanoparticles for Photodynamic Therapy and Other Cancer Therapeutics. Theranostics 2013, 3 (5), 317–330. https://doi.org/10.7150/thno.5284.
(68) Guo, H.; Qian, H.; Idris, N. M.; Zhang, Y. Singlet Oxygen-Induced Apoptosis of Cancer Cells Using Upconversion Fluorescent Nanoparticles as a Carrier of Photosensitizer. Nanomedicine Nanotechnology, Biol. Med. 2010, 6 (3), 486–495. https://doi.org/10.1016/j.nano.2009.11.004.
(69) Wang, C.; Tao, H.; Cheng, L.; Liu, Z. Near-Infrared Light Induced in Vivo Photodynamic Therapy of Cancer Based on Upconversion Nanoparticles. Biomaterials 2011, 32 (26), 6145–6154. https://doi.org/10.1016/j.biomaterials.2011.05.007.
(70) Ju, Q.; Chen, X.; Ai, F.; Peng, D.; Lin, X.; Kong, W.; Shi, P.; Zhu, G.; Wang, F. An Upconversion Nanoprobe Operating in the First Biological Window. J. Mater. Chem. B 2015, 3 (17), 3548–3555. https://doi.org/10.1039/c5tb00025d.
(71) Freitag, L.; Ernst, A.; Thomas, M.; Prenzel, R.; Wahlers, B.; Macha, H. N. Sequential Photodynamic Therapy (PDT) and High Dose Brachytherapy for Endobronchial Tumour
Control in Patients with Limited Bronchogenic Carcinoma. Thorax 2004, 59 (9), 790–793. https://doi.org/10.1136/thx.2003.013599.
(72) Benov, L. Photodynamic Therapy: Current Status and Future Directions. In Medical Principles and Practice; S. Karger AG, 2015; Vol. 24, pp 14–28. https://doi.org/10.1159/000362416.
(73) Naccache, R.; Yu, Q.; Capobianco, J. A. The Fluoride Host: Nucleation, Growth, and Upconversion of Lanthanide-Doped Nanoparticles. Adv. Opt. Mater. 2015, 3 (4), 482–509. https://doi.org/10.1002/adom.201400628.
(74) Mandl, G. A.; Van der Heggen, D.; Cooper, D. R.; Joos, J. J.; Seuntjens, J.; Smet, P. F.; Capobianco, J. A. On a Local (de-)Trapping Model for Highly Doped Pr 3+ Radioluminescent and Persistent Luminescent Nanoparticles. Nanoscale 2020, 12 (40), 20759–20766. https://doi.org/10.1039/D0NR06577C.
(75) Brix, N.; Samaga, D.; Belka, C.; Zitzelsberger, H.; Lauber, K. Analysis of Clonogenic Growth in Vitro. Nat. Protoc. 2021, 16 (11), 4963–4991. https://doi.org/10.1038/s41596-021-00615-0.
(76) Merck. Cell Dissociation with Trypsin | Mechanism in cell culture | Sigma-Aldrich https://www.sigmaaldrich.com/technical-documents/articles/biology/cell-dissociation-with-trypsin.html (accessed Jun 1, 2020).
(77) ThermoFisher Scientific. Useful Numbers for Cell Culture | Thermo Fisher Scientific - CA https://www.thermofisher.com/ca/en/home/references/gibco-cell-culture-basics/cell-culture-protocols/cell-culture-useful-numbers.html (accessed Jun 16, 2020).
(78) Mandl, G. A.; Van Der Heggen, D.; Cooper, D. R.; Smet, P.; Seuntjens, J.; Capobianco, J. A. Manuscript in Preparation; 2020.
(79) Cooper, D. R.; Capobianco, J. A.; Seuntjens, J. Radioluminescence Studies of Colloidal Oleate-Capped β-Na(Gd,Lu)F 4 :Ln 3+ Nanoparticles (Ln = Ce, Eu, Tb). Nanoscale 2018, 10 (16), 7821–7832. https://doi.org/10.1039/C8NR01262H.
(80) Ouyang, J.; Yin, D.; Cao, X.; Wang, C.; Song, K.; Liu, B.; Zhang, L.; Han, Y.; Wu, M. Synthesis of NaLuF 4 -Based Nanocrystals and Large Enhancement of Upconversion Luminescence of NaLuF 4 :Gd, Yb, Er by Coating an Active Shell for Bioimaging. Dalt.
Trans. 2014, 43 (37), 14001–14008. https://doi.org/10.1039/C4DT00509K.
(81) Mai, H.-X.; Zhang, Y.-W.; Si, R.; Yan, Z.-G.; Sun, L.; You, L.-P.; Yan, C.-H. High-Quality Sodium Rare-Earth Fluoride Nanocrystals: Controlled Synthesis and Optical Properties. J. Am. Chem. Soc. 2006, 128 (19), 6426–6436. https://doi.org/10.1021/ja060212h.
(82) Li, J.; Wang, W.; Liu, B.; Duan, G.; Liu, Z. Enhanced Dy3+ White Emission via Energy Transfer in Spherical (Lu,Gd)3Al5O12 Garnet Phosphors. Sci. Rep. 2020, 10 (1), 1–9. https://doi.org/10.1038/s41598-020-59232-8.
(83) Tang, Y.; Hu, J.; Elmenoufy, A. H.; Yang, X. Highly Efficient FRET System Capable of Deep Photodynamic Therapy Established on X-Ray Excited Mesoporous LaF3:Tb Scintillating Nanoparticles. ACS Appl. Mater. Interfaces 2015, 7 (22), 12261–12269. https://doi.org/10.1021/acsami.5b03067.
(84) Li, Y.; Chen, B.; Tong, L.; Zhang, X.; Xu, S.; Li, X.; Zhang, J.; Sun, J.; Wang, X.; Zhang, Y.; Sui, G.; Zhang, Y.; Zhang, X.; Xia, H. A Temperature Self-Monitoring NaYF4:Dy3+/Yb3+@NaYF4:Er3+/Yb3+ Core-Shell Photothermal Converter for Photothermal Therapy Application. Results Phys. 2019, 15, 102704. https://doi.org/10.1016/j.rinp.2019.102704.
(85) Zhang, J.; Hao, Z.; Li, J.; Zhang, X.; Luo, Y.; Pan, G. Observation of Efficient Population of the Red-Emitting State from the Green State by Non-Multiphonon Relaxation in the Er3+-Yb3+ System. Light Sci. Appl. 2015, 4 (1), e239. https://doi.org/10.1038/lsa.2015.12.
(86) Sousa, J. F.; Alves, R. T.; Rego-Filho, F. G.; Gouveia-Neto, A. S. Erbium-to-Dysprosium Energy-Transfer Mechanism and Visible Luminescence in Lead-Cadmium-Fluorogermanate Glass Excited at 405 Nm. Chem. Phys. Lett. 2019, 723 (December 2018), 28–32. https://doi.org/10.1016/j.cplett.2019.03.017.
(87) Hufner, S.; Judd, B. R. Optical Spectra of Transparent Rare Earth Compounds. Phys. Today 1979, 32 (3), 76–77. https://doi.org/10.1063/1.2995463.
(88) Maurizio, S. L.; Tessitore, G.; Mandl, G. A.; Capobianco, J. A. Luminescence Dynamics and Enhancement of the UV and Visible Emissions of Tm3+ in LiYF4:Yb3+,Tm3+ Upconverting Nanoparticles. Nanoscale Adv. 2019, 1 (11), 4492–4500. https://doi.org/10.1039/c9na00556k.
(89) Wu, X.; Tang, Z.; Hu, S.; Yan, H.; Xi, Z.; Liu, Y. NaLuF4:Yb3+,Er3+ Bifunctional Microcrystals Codoped with Gd3+ or Dy3+ Ions: Enhanced Upconversion Luminescence and Ferromagnetic-Paramagnetic Transition. J. Alloys Compd. 2016, 684, 105–111. https://doi.org/10.1016/j.jallcom.2016.05.074.
(90) Tang, J.; Luo, L.; Li, W.; Wang, J.; Du, P. Ethylene Glycol Associated Facile Preparation and Luminescent Behaviors of RE (RE = Sm3+, Dy3+) Ions Activated NaLuF4 Nanoparticles. Opt. Mater. (Amst). 2021, 120, 111463. https://doi.org/10.1016/j.optmat.2021.111463.
(91) Hasegawa, Y.; Wada, Y.; Yanagida, S. Strategies for the Design of Luminescent Lanthanide(III) Complexes and Their Photonic Applications. Journal of Photochemistry and Photobiology C: Photochemistry Reviews. Elsevier December 31, 2004, pp 183–202. https://doi.org/10.1016/j.jphotochemrev.2004.10.003.
(92) Andrews, D. L.; Rodríguez, J. Resonance Energy Transfer: Spectral Overlap, Efficiency, and Direction. J. Chem. Phys. 2007, 127 (8), 084509. https://doi.org/10.1063/1.2759489.
(93) Dorset, D. L. X-Ray Diffraction: A Practical Approach. Microsc. Microanal. 1998, 4 (5), 513–515. https://doi.org/10.1017/S143192769800049X.
(94) Bogachev, N. A.; Betina, A. A.; Bulatova, T. S.; Nosov, V. G.; Kolesnik, S. S.; Tumkin, I. I.; Ryazantsev, M. N.; Skripkin, M. Y.; Mereshchenko, A. S. Lanthanide-Ion-Doping Effect on the Morphology and the Structure of NaYF4:Ln3+ Nanoparticles. Nanomaterials 2022, 12 (17), 2972. https://doi.org/10.3390/nano12172972.
(95) Sousa, J. F.; Alves, R. T.; Rego-Filho, F. G.; Gouveia-Neto, A. S. Erbium-to-Dysprosium Energy-Transfer Mechanism and Visible Luminescence in Lead-Cadmium-Fluorogermanate Glass Excited at 405 Nm. Chem. Phys. Lett. 2019, 723, 28–32. https://doi.org/10.1016/j.cplett.2019.03.017.
(96) Majewski, M. R.; Woodward, R. I.; Jackson, S. D. Dysprosium Mid‐Infrared Lasers: Current Status and Future Prospects. Laser Photon. Rev. 2020, 14 (3), 1900195. https://doi.org/10.1002/lpor.201900195.
(97) Wang, J.; Zhu, X.; Mollaee, M.; Zong, J.; Peyhambarian, N. Efficient Energy Transfer from Er 3+ to Ho 3+ and Dy 3+ in ZBLAN Glass. Opt. Express 2020, 28 (4), 5189.
(98) Huang, F.; Yang, T.; Wang, S.; Lin, L.; Hu, T.; Chen, D. Temperature Sensitive Cross Relaxation between Er 3+ Ions in Laminated Hosts: A Novel Mechanism for Thermochromic Upconversion and High Performance Thermometry. J. Mater. Chem. C 2018, 6 (45), 12364–12370. https://doi.org/10.1039/C8TC04733B.
(99) Chiossi, F.; Vasiukov, S.; Borghesani, A. F.; Braggio, C.; Di Lieto, A.; Tonelli, M.; Carugno, G. High Infrared Light Yield of Erbium-Doped Fluoride Crystals. J. Lumin. 2020, 219 (November 2019), 116883. https://doi.org/10.1016/j.jlumin.2019.116883.
(100) Bai, Z.; Fujii, M.; Hasegawa, T.; Imakita, K.; Mizuhata, M.; Hayashi, S. Efficient Ultraviolet-Blue to near-Infrared Downconversion in Bi–Dy–Yb-Doped Zeolites. J. Phys. D. Appl. Phys. 2011, 44 (45), 455301. https://doi.org/10.1088/0022-3727/44/45/455301.
(101) Sharafi, Z.; Bakhshi, B.; Javidi, J.; Adrangi, S. Synthesis of Silica-Coated Iron Oxide Nanoparticles: Preventing Aggregation without Using Additives or Seed Pretreatment. Iran. J. Pharm. Res. IJPR 2018, 17 (1), 386–395.
(102) Bogdan, N.; Vetrone, F.; Ozin, G. A.; Capobianco, J. A. Synthesis of Ligand-Free Colloidally Stable Water Dispersible Brightly Luminescent Lanthanide-Doped Upconverting Nanoparticles. Nano Lett. 2011, 11 (2), 835–840. https://doi.org/10.1021/nl1041929.
(103) Sun, W.; Zhou, Z.; Pratx, G.; Chen, X.; Chen, H. Nanoscintillator-Mediated X-Ray Induced Photodynamic Therapy for Deep-Seated Tumors: From Concept to Biomedical Applications. Theranostics 2020, 10 (3), 1296–1318. https://doi.org/10.7150/thno.41578.
(104) Liang, L.; Care, A.; Zhang, R.; Lu, Y.; Packer, N. H.; Sunna, A.; Qian, Y.; Zvyagin, A. V. Facile Assembly of Functional Upconversion Nanoparticles for Targeted Cancer Imaging and Photodynamic Therapy. ACS Appl. Mater. Interfaces 2016, 8 (19), 11945–11953. https://doi.org/10.1021/acsami.6b00713.
(105) Rosenberg, D. J.; Alayoglu, S.; Kostecki, R.; Ahmed, M. Synthesis of Microporous Silica Nanoparticles to Study Water Phase Transitions by Vibrational Spectroscopy. Nanoscale Adv. 2019, 1 (12), 4878–4887. https://doi.org/10.1039/C9NA00544G.
(106) Cauda, V.; Argyo, C.; Bein, T. Impact of Different PEGylation Patterns on the Long-Term
Bio-Stability of Colloidal Mesoporous Silica Nanoparticles. J. Mater. Chem. 2010, 20 (39), 8693–8699. https://doi.org/10.1039/c0jm01390k.
(107) Pham, A. L. T.; Sedlak, D. L.; Doyle, F. M. Dissolution of Mesoporous Silica Supports in Aqueous Solutions: Implications for Mesoporous Silica-Based Water Treatment Processes. Appl. Catal. B Environ. 2012, 126, 258–264. https://doi.org/10.1016/j.apcatb.2012.07.018.
(108) Wang, Y.; Liu, K.; Liu, X.; Dohnalová, K.; Gregorkiewicz, T.; Kong, X.; Aalders, M. C. G.; Buma, W. J.; Zhang, H. Critical Shell Thickness of Core/Shell Upconversion Luminescence Nanoplatform for FRET Application. J. Phys. Chem. Lett. 2011, 2 (17), 2083–2088. https://doi.org/10.1021/jz200922f.
(109) Han, R.; Shi, J.; Liu, Z.; Wang, H.; Wang, Y. Fabrication of Mesoporous-Silica-Coated Upconverting Nanoparticles with Ultrafast Photosensitizer Loading and 808 Nm NIR-Light-Triggering Capability for Photodynamic Therapy. Chem. - An Asian J. 2017, 12 (17), 2197–2201. https://doi.org/10.1002/asia.201700836.
(110) Lai, J.; Shah, B. P.; Zhang, Y.; Yang, L.; Lee, K. B. Real-Time Monitoring of ATP-Responsive Drug Release Using Mesoporous-Silica-Coated Multicolor Upconversion Nanoparticles. ACS Nano 2015, 9 (5), 5234–5245. https://doi.org/10.1021/acsnano.5b00641.
(111) Zhou, Y.; Quan, G.; Wu, Q.; Zhang, X.; Niu, B.; Wu, B.; Huang, Y.; Pan, X.; Wu, C. Mesoporous Silica Nanoparticles for Drug and Gene Delivery. Acta Pharm. Sin. B 2018, 8 (2), 165–177. https://doi.org/10.1016/j.apsb.2018.01.007.
(112) Han, R.; Tang, K.; Hou, Y.; Yu, J.; Wang, C.; Wang, Y. Fabrication of Core/Shell/Shell Structure Nanoparticle with Anticancer Drug and Dual-Photosensitizer Co-Loading for Synergistic Chemotherapy and Photodynamic Therapy. Microporous Mesoporous Mater. 2020, 297 (January), 110049. https://doi.org/10.1016/j.micromeso.2020.110049.
(113) Nahorniak, M.; Pop-Georgievski, O.; Velychkivska, N.; Filipová, M.; Rydvalová, E.; Gunár, K.; Matouš, P.; Kostiv, U.; Horák, D. Rose Bengal-Modified Upconverting Nanoparticles: Synthesis, Characterization, and Biological Evaluation. Life 2022, 12 (9), 1383. https://doi.org/10.3390/life12091383.
(114) Wawrzyńczyk, D.; Cichy, B.; Zaręba, J. K.; Bazylińska, U. On the Interaction between Up-
Converting NaYF 4 :Er 3+ ,Yb 3+ Nanoparticles and Rose Bengal Molecules Constrained within the Double Core of Multifunctional Nanocarriers. J. Mater. Chem. C 2019, 7 (47), 15021–15034. https://doi.org/10.1039/C9TC04163J.
(115) Ho, T.-H.; Yang, C.-H.; Jiang, Z.-E.; Lin, H.-Y.; Chen, Y.-F.; Wang, T.-L. NIR-Triggered Generation of Reactive Oxygen Species and Photodynamic Therapy Based on Mesoporous Silica-Coated LiYF4 Upconverting Nanoparticles. Int. J. Mol. Sci. 2022, 23 (15), 8757. https://doi.org/10.3390/ijms23158757.
(116) Chang, C. C.; Yang, Y. T.; Yang, J. C.; Wu, H. Da; Tsai, T. Absorption and Emission Spectral Shifts of Rose Bengal Associated with DMPC Liposomes. Dye. Pigment. 2008, 79 (2), 170–175. https://doi.org/10.1016/j.dyepig.2008.02.003.
(117) International Organization for Standardization (ISO). ISO 10993-5:2019 Biological Evaluation of Medical Devices - Part 5: Tests for in Vitro Cytotoxicity. 2019.
(118) Huang, X.; Teng, X.; Chen, D.; Tang, F.; He, J. The Effect of the Shape of Mesoporous Silica Nanoparticles on Cellular Uptake and Cell Function. Biomaterials 2010, 31 (3), 438–448. https://doi.org/10.1016/j.biomaterials.2009.09.060.
(119) Kostiv, U.; Šlouf, M.; Macková, H.; Zhigunov, A.; Engstová, H.; Smolková, K.; Ježek, P.; Horák, D. Silica-Coated Upconversion Lanthanide Nanoparticles: The Effect of Crystal Design on Morphology, Structure and Optical Properties. Beilstein J. Nanotechnol. 2015, 6 (1), 2290–2299. https://doi.org/10.3762/bjnano.6.235.
(120) Ren, Z. X.; Yu, H. Bin; Li, J. S.; Shen, J. L.; Du, W. Sen. Suitable Parameter Choice on Quantitative Morphology of A549 Cell in Epithelial-Mesenchymal Transition. Biosci. Rep. 2015, 35 (3), 1–7. https://doi.org/10.1042/BSR20150070.
(121) Hsu, C.-Y.; Chen, C.-W.; Yu, H.-P.; Lin, Y.-F.; Lai, P.-S. Bioluminescence Resonance Energy Transfer Using Luciferase-Immobilized Quantum Dots for Self-Illuminated Photodynamic Therapy. Biomaterials 2013, 34 (4), 1204–1212. https://doi.org/10.1016/j.biomaterials.2012.08.044.
(122) Marill, J.; Anesary, N. M.; Zhang, P.; Vivet, S.; Borghi, E.; Levy, L.; Pottier, A. Hafnium Oxide Nanoparticles: Toward an in Vitropredictive Biological Effect? Radiat. Oncol. 2014, 9 (1), 150. https://doi.org/10.1186/1748-717X-9-150.
(123) Zhang, P.; Marill, J.; Darmon, A.; Mohamed Anesary, N.; Lu, B.; Paris, S. NBTXR3 Radiotherapy-Activated Functionalized Hafnium Oxide Nanoparticles Show Efficient Antitumor Effects Across a Large Panel of Human Cancer Models. Int. J. Nanomedicine 2021, Volume 16, 2761–2773. https://doi.org/10.2147/IJN.S301182.
(124) Ren, Y.; Rosch, J. G.; Landry, M. R.; Winter, H.; Khan, S.; Pratx, G.; Sun, C. Tb-Doped Core–Shell–Shell Nanophosphors for Enhanced X-Ray Induced Luminescence and Sensitization of Radiodynamic Therapy. Biomater. Sci. 2021, 9 (2), 496–505. https://doi.org/10.1039/D0BM00897D.
(125) Clement, S.; Chen, W.; Deng, W.; Goldys, E. M. X-Ray Radiation-Induced and Targeted Photodynamic Therapy with Folic Acid-Conjugated Biodegradable Nanoconstructs. Int. J. Nanomedicine 2018, 13, 3553–3570. https://doi.org/10.2147/IJN.S164967.
(126) Liu, P. D.; Jin, H.; Guo, Z.; Ma, J.; Zhao, J.; Li, D.; Wu, H.; Gu, N. Silver Nanoparticles Outperform Gold Nanoparticles in Radiosensitizing U251 Cells in Vitro and in an Intracranial Mouse Model of Glioma. Int. J. Nanomedicine 2016, Volume 11, 5003–5014. https://doi.org/10.2147/IJN.S115473.
(127) Gu, X.; Shen, C.; Li, H.; Goldys, E. M.; Deng, W. X-Ray Induced Photodynamic Therapy (PDT) with a Mitochondria-Targeted Liposome Delivery System. J. Nanobiotechnology 2020, 18 (1), 87. https://doi.org/10.1186/s12951-020-00644-z.
(128) Mishchenko, T.; Balalaeva, I.; Gorokhova, A.; Vedunova, M.; Krysko, D. V. Which Cell Death Modality Wins the Contest for Photodynamic Therapy of Cancer? Cell Death Dis. 2022, 13 (5), 455. https://doi.org/10.1038/s41419-022-04851-4.
(129) Yang, H. J.; Kim, N.; Seong, K. M.; Youn, H.; Youn, B. Investigation of Radiation-Induced Transcriptome Profile of Radioresistant Non-Small Cell Lung Cancer A549 Cells Using RNA-Seq. PLoS One 2013, 8 (3), e59319. https://doi.org/10.1371/journal.pone.0059319.
(130) de Kraker, J.; Hoefnagel, C. A.; Voûte, P. A. 131I-Rose Bengal Therapy in Hepatoblastoma Patients. Eur. J. Cancer Clin. Oncol. 1991, 27 (5), 613–615. https://doi.org/10.1016/0277-5379(91)90229-7.
(131) Subiel, A.; Ashmore, R.; Schettino, G. Standards and Methodologies for Characterizing Radiobiological Impact of High-Z Nanoparticles. Theranostics 2016, 6 (10), 1651–1671.
(132) Neuer, A. L.; Gerken, L. R. H.; Keevend, K.; Gogos, A.; Herrmann, I. K. Uptake, Distribution and Radio-Enhancement Effects of Gold Nanoparticles in Tumor Microtissues. Nanoscale Adv. 2020, 2 (7), 2992–3001. https://doi.org/10.1039/D0NA00256A.
(133) Absher, M. Hemocytometer Counting. In Tissue Culture; Elsevier, 1973; pp 395–397. https://doi.org/10.1016/b978-0-12-427150-0.50098-x.
All items in Spectrum are protected by copyright, with all rights reserved. The use of items is governed by Spectrum's terms of access.

Repository Staff Only: item control page

Downloads per month over past year

Research related to the current document (at the CORE website)
- Research related to the current document (at the CORE website)
Back to top Back to top