Nanosized luminescent hydroxyapatite doped with terbium: synthesis and characterization
DOI: https://doi.org/10.15407/hftp16.01.115
Abstract
The aim of this work is to synthesize a new nanostructured biocompatible material with a high ability to X-ray-induced luminescence. Terbium-doped hydroxyapatite known for its biocompatibility and non-toxicity was synthesized in two ways: 1) by precipitation of Ca2+ and Tb3+ ions with (NH4)2HPO4 solution in the presence of various biocompatible modifiers (CTAB, PEG-2000, trisodium citrate dihydrate); 2) by cationic substitution of hydroxyapatite in the presence of the same modifiers at pH 4 and pH 6. The stoichiometric ratio (Ca+Tb)/P in the initial solutions was maintained at the level of biological hydroxyapatite.
Based on the results of DLS, ELS, and X-ray-induced luminescence studies, it was found that the sample with the best key properties, such as ζ-potential and X-ray-induced luminescence, was the sample of hydroxyapatite doped with 5% (mol), synthesized by co-precipitation procedure in presence of trisodium citrate dihydrate. Further studies by TEM, FTIR, FT-NIR, TG/DTG/DTA, XRD, low-temperature nitrogen adsorption-desorption, and ICP-AES confirm that the sample has a surface functionalized with citrate groups, which causes high colloidal stability and can provide high adsorption potential. The value of the (Ca+Tb)/P ratio is 2.21 (wt %), which is close to that of biological hydroxyapatite. The nanocomposite is characterized by high X-ray-induced luminescence and may be promising for adsorption immobilization of biologically active compounds.
The results of the study indicate that the optimized conditions for the synthesis of nanophosphors have been found, which are potential candidates for biomedical applications, given their luminescent properties, low toxicity, and the possibility of further surface functionalization for adsorption saturation with molecules of medical interest.
Keywords
References
1. Srinivasan M., Rajabi M., Mousa S. Multifunctional Nanomaterials and Their Applications in Drug Delivery and Cancer Therapy. Nanomaterials. 2015. 5(4): 1690. https://doi.org/10.3390/nano5041690
2. Reiss P., Protière M., Li L. Core/Shell Semiconductor Nanocrystals. Small. 2009. 5(2): 154. https://doi.org/10.1002/smll.200800841
3. Lin M., Zhao Y., Wang S., Liu M., Duan Z., Chen Y., Li F., Xu F., Lu T. Recent Advances in Synthesis and Surface Modification of Lanthanide-doped Upconversion Nanoparticles for Biomedical Applications. Biotechnol. Adv., 2012. 30(6): 1551. https://doi.org/10.1016/j.biotechadv.2012.04.009
4. Zheng B., Fan J., Chen B., Qin X., Wang J., Wang F., Deng R., Liu X. Rare-Earth Doping in Nanostructured Inorganic Materials. Chem. Rev. 2022. 122(6): 5519. https://doi.org/10.1021/acs.chemrev.1c00644
5. Kang X., Huang S., Yang P., Ma P., Yang D., Lin J. Preparation of Luminescent and Mesoporous Eu3+/Tb3+ Doped Calcium Silicate Microspheres as Drug Carriers via a Template Route. Dalton Trans. 2011. 40(9): 1873. https://doi.org/10.1039/C0DT01390K
6. Wu Y., Wang Y., He D., Fu M., Chen Z., Li Y. Spherical Zn2SiO4:Eu3+@SiO2 Phosphor Particles in Core-shell Structure: Synthesis and Characterization. J. Lumin. 2010. 130(10): 1768. https://doi.org/10.1016/j.jlumin.2010.04.008
7. Zhong S.-L., Lu Y., Gao M.-R., Liu S.-J., Peng J., Zhang L.-C., Yu S.-H. Monodisperse Mesocrystals of YF3 and Ce3+/Ln3+ (Ln = Tb, Eu) Co-Activated YF3: Shape Control Synthesis, Luminescent Properties, and Biocompatibility. Chem. Eur. J. 2012. 18(17): 5222. https://doi.org/10.1002/chem.201102840
8. Yang M., You H., Liu K., Zheng Y., Guo N., Zhang H. Low-Temperature Coprecipitation Synthesis and Luminescent Properties of LaPO4:Ln3+ (Ln3+ = Ce3+, Tb3+) Nanowires and LaPO4:Ce3+, Tb3+/LaPO4 Core/Shell Nanowires. Inorg. Chem. 2010. 49(11): 4996.
9. Liu H., Chen F., Xi P., Chen B., Huang L., Cheng J., Shao C., Wang J., Bai D., Zeng Z. Biocompatible Fluorescent Hydroxyapatite: Synthesis and Live Cell Imaging Applications. J. Phys. Chem. C. 2011. 115(38): 18538. https://doi.org/10.1021/jp206843w
10. Krishnapriya T.K., Deepti A., Chakrapani P.S., Asha A.S., Jayaraj M.K. Biocompatible, Europium-Doped Fluorapatite Nanoparticles as a Wide-Range pH Sensor. J. Fluoresc. 2023. 34: 2543. https://doi.org/10.1007/s10895-023-03461-3
11. Lara-Ochoa S., Ortega-Lara W., Guerrero-Beltrán C.E. Hydroxyapatite Nanoparticles in Drug Delivery: Physicochemistry and Applications. Pharmaceutics. 2021. 13(10): 1642. https://doi.org/10.3390/pharmaceutics13101642
12. Uskokovic V., Desai T.A. Phase Composition Control of Calcium Phosphate Nanoparticles for Tunable Drug Delivery Kinetics and Treatment of Osteomyelitis. I. Preparation and drug release. J. Biomed. Mater. Res. A. 2013. 101(5): 1416. https://doi.org/10.1002/jbm.a.34426
13. Matsumoto T., Okazaki M., Inoue M., Yamaguchi S., Kusunose T., Toyonaga T., Hamada Y., Takahashi J. Hydroxyapatite Particles as a Controlled Release Carrier of Protein. Biomaterials. 2004. 25(17): 3807. https://doi.org/10.1016/j.biomaterials.2003.10.081
14. Zhang S., Ma X., Sha D., Qian J., Yuan Y., Liu C. A Novel Strategy for Tumor Therapy: Targeted, PAA-Functionalized Nano-hydroxyapatite Nanomedicine. J. Mater. Chem. B. 2020. 8(41): 9589. https://doi.org/10.1039/D0TB01603A
15. Venkatasubbu G.D., Ramasamy S., Avadhani G.S., Ramakrishnan V., Kumar J. Surface Modification and Paclitaxel Drug Delivery of Folic Acid Modified Polyethylene Glycol Functionalized Hydroxyapatite Nanoparticles. Powder Technol. 2013. 235: 437. https://doi.org/10.1016/j.powtec.2012.11.003
16. Gu M., Li W., Jiang L., Li X. Recent Progress of Rare Earth Doped Hydroxyapatite Nanoparticles: Luminescence Properties, Synthesis and Biomedical Applications. Acta Biomater. 2022. 148: 22. https://doi.org/10.1016/j.actbio.2022.06.006
17. Neacsu I.A., Stoica A.E., Vasile B.S., Andronescu E. Luminescent Hydroxyapatite Doped with Rare Earth Elements for Biomedical Applications. Nanomaterials. 2019. 9(2): 239. https://doi.org/10.3390/nano9020239
18. De Lama-Odría M.d.C., Valle L.J.d., Puiggalí J. Lanthanides-Substituted Hydroxyapatite for Biomedical Applications. Int. J. Mol. Sci. 2023. 24(4): 3446. https://doi.org/10.3390/ijms24043446
19. Šupová M. Substituted Hydroxyapatites for Biomedical Applications: a Review. Ceram. Int. 2015. 41(8): 9203. https://doi.org/10.1016/j.ceramint.2015.03.316
20. Kusyak A., Petranovska A., Oranska O., Turanska S., Shuba Ya., Kravchuk D., Kravchyk L., Sotkis G., Nazarenko V., Kravchuk R., Dubok V., Bur'yanov O., Chornyi V., Sobolevs'kyy Yu., Gorbyk P. Synthesis and Properties of Nanodispersed Luminescent Structures Based on Lanthanum Fluoride and Phosphate for Optopharmacology and Photodynamic Therapy of Tumor Diseases Localized in Cranial Organs and Bone Tissues. Chapter 3. (New York: Nova Science Publishers Inc., 2023).
21. Zilm M.E., Chen L., Sharma V., McDannald A., Jain M., Ramprasad R., Wei M. Hydroxyapatite Substituted by Transition Metals: Experiment and Theory. Phys. Chem. Chem. Phys. 2016. 18(24): 16457. https://doi.org/10.1039/C6CP00474A
22. Tite T., Popa A.-C., Balescu L.M., Bogdan I.M., Pasuk I., Ferreira J.M.F., Stan G.E. Cationic Substitutions in Hydroxyapatite: Current Status of the Derived Biofunctional Effects and Their In Vitro Interrogation Methods. Materials. 2018. 11(11): 2081. https://doi.org/10.3390/ma11112081
23. Chen M.-H., Yoshioka T., Ikoma T., Hanagata N., Lin F.-H., Tanaka J. Photoluminescence and Doping Mechanism of Theranostic Eu3+/Fe3+ Dual-doped Hydroxyapatite Nanoparticles. Sci. Technol. Adv. Mater. 2014. 15(5): 055005. https://doi.org/10.1088/1468-6996/15/5/055005
24. Alshemary A.Z., Akram M., Goh Y.-F., Abdul Kadir M.R., Abdolahi A., Hussain R. Structural Characterization, Optical Properties and In Vitro Bioactivity of Mesoporous Erbium-doped Hydroxyapatite. J. Alloys Compd. 2015. 645: 478. https://doi.org/10.1016/j.jallcom.2015.05.064
25. Ahmed L.O., Bulut N., Bañares L., Kaygili O., Kebiroglu M., Ates T., Koytepe S., Ates B. Exploring the Electronic Band Structure, Spectroscopic Signatures, and Structural Properties of Er3+-based Hydroxyapatites Co-doped with Ce3+ Ions. Inorg. Chem. Commun. 2023. 155(37): 111067. https://doi.org/10.1016/j.inoche.2023.111067
26. Wei Y., He Y., Li X., Chen H., Deng X. Cellular Uptake and Delivery-Dependent Effects of Tb3+-Doped Hydroxyapatite Nanorods. Molecules. 2017. 22(7): 1043. https://doi.org/10.3390/molecules22071043
27. Yin H., Li Y., Bai J., Ma M., Liu J. Effect of Calcinations Temperature on the Luminescence Intensity and Fluorescent Lifetime of Tb3+-doped Hydroxyapatite (Tb-HA) Nanocrystallines. J. Materiomics. 2017. 3(2): 144. https://doi.org/10.1016/j.jmat.2016.11.004
28. Ghosh R., Sarkar R., Paul S. Development of Machinable Hydroxyapatite-Lanthanum Phosphate Composite for Biomedical Applications. Mater. Design. 2016. 106: 161. https://doi.org/10.1016/j.matdes.2016.05.104
29. Venkatasubbu G.D., Ramasamy S., Avadhani G.S., Ramakrishnan V., Kumar J. Surface Modification and Paclitaxel Drug Delivery of Folic Acid Modified Polyethylene Glycol Functionalized Hydroxyapatite Nanoparticles. Powder Technol. 2013. 235: 437. https://doi.org/10.1016/j.powtec.2012.11.003
30. Cawthray J.F., Creagh A.L., Haynes C.A., Orvig C. Ion Exchange in Hydroxyapatite with Lanthanides. Inorg. Chem. 2015. 54(4): 1440. https://doi.org/10.1021/ic502425e
31. Li L., Liu Y., Tao J., Zhang M., Pan H., Xu X., Tang R. Surface Modification of Hydroxyapatite Nanocrystallite by a Small Amount of Terbium Provides a Biocompatible Fluorescent Probe. J. Phys. Chem. C. 2008. 112(32): 12219. https://doi.org/10.1021/jp8026463
32. Huang S., Zhu J., Zhou K. Synthesis and Luminescence Properties of Tb3+-Doped Hydroxyapatites. Adv. Mater. Res. 2012. 399-401: 1582. https://doi.org/10.4028/www.scientific.net/AMR.399-401.1582
33. Yin H., Li Y., Bai J., Ma M., Liu J. Effect of Calcinations Temperature on the Luminescence Intensity and Fluorescent Lifetime of Tb3+-doped Hydroxyapatite (Tb-HA) Nanocrystallines. J. Materiomics. 2017. 3(2): 144. https://doi.org/10.1016/j.jmat.2016.11.004
34. Ou X., Qin X., Huang B., Zan J., Wu Q., Hong Z., Xie L., Bian H., Yi Z., Chen X., Wu Y., Song X., Li J., Chen Q., Yang H., Liu X. High-resolution X-ray Luminescence Extension Imaging. Nature. 2021. 590(7846): 410. https://doi.org/10.1038/s41586-021-03251-6
35. Xu Z., Li Y., Liu Z., Wang D. UV and X-ray Excited Luminescence of Tb3+-doped ZnGa2O4 Phosphors. J. Alloys Compd. 2005. 391(1-2): 202. https://doi.org/10.1016/j.jallcom.2004.08.088
36. Ciobanu C.S., Iconaru S.L., Massuyeau F., Constantin L.V., Costescu A., Predoi D. Synthesis, Structure, and Luminescent Properties of Europium-Doped Hydroxyapatite Nanocrystalline Powders. J. Nanomater. 2012. 212: 942801. https://doi.org/10.1155/2012/942801
37. Wei Y., He Y., Li X., Chen H., Deng X. Cellular Uptake and Delivery-Dependent Effects of Tb3+-Doped Hydroxyapatite Nanorods. Molecules. 2017. 22(7): 1043. https://doi.org/10.3390/molecules22071043
38. Paduraru A.V., Oprea O., Musuc A.M., Vasile B.S., Iordache F., Andronescu E. Influence of Terbium Ions and Their Concentration on the Photoluminescence Properties of Hydroxyapatite for Biomedical Applications. Nanomaterials. 2021. 11(9): 2442. https://doi.org/10.3390/nano11092442
39. Gómez-Morales J., Fernández-Penas R., Acebedo-Martínez F.J., Romero-Castillo I., Verdugo-Escamilla C., Choquesillo-Lazarte D., Esposti L.D., Jiménez-Martínez Y., Fernández-Sánchez J.F., Iafisco M., Boulaiz H. Luminescent Citrate-Functionalized Terbium-Substituted Carbonated Apatite Nanomaterials: Structural Aspects, Sensitized Luminescence, Cytocompatibility, and Cell Uptake Imaging. Nanomaterials. 2022. 12(8): 1257. https://doi.org/10.3390/nano12081257
40. Daryan S. H., Khavandi A., Javadpour, J. Surface Engineered Hollow Hydroxyapatite Microspheres: Hydrothermal Synthesis and Growth Mechanisms. Solid State Sci. 2020. 106: 106301. https://doi.org/10.1016/j.solidstatesciences.2020.106301
41. Shang H.-B., Chen F., Wu J., Qi C., Lu B.-Q., Chen X., Zhu Y.-J. Multifunctional Biodegradable Terbium-doped Calcium Phosphate Nanoparticles: Facile Preparation, pH-sensitive Drug Release and In Vitro Bioimaging. RSC Adv., 2014. 4(95): 53122. https://doi.org/10.1039/C4RA09902H
42. Simon A.T., Dutta D., Chattopadhyay A., Ghosh S. S. Copper Nanocluster-Doped Luminescent Hydroxyapatite Nanoparticles for Antibacterial and Antibiofilm Applications. ACS Omega. 2019. 4(3): 4697. https://doi.org/10.1021/acsomega.8b03076
43. De Lama-Odría M.d.C., Valle L.J.d., Puiggalí J. Lanthanides-Substituted Hydroxyapatite for Biomedical Applications. Int. J. Mol. Sci. 2023. 24(4): 3446. https://doi.org/10.3390/ijms24043446
44. Gu M., Li W., Jiang L., Li X. Recent Progress of Rare Earth Doped Hydroxyapatite Nanoparticles: Luminescence Properties, Synthesis and Biomedical Applications. Acta Biomater. 2022. 148: 22. https://doi.org/10.1016/j.actbio.2022.06.006
45. Ignjatović N.L., Mančić L., Vuković M., Stojanović Z., Nikolić M.G., Škapin S., Jovanović S., Veselinović L., Uskoković V., Lazić S., Marković S., Lazarević M.M., Uskoković D.P. Rare-earth (Gd3+, Yb3+/Tm3+, Eu3+) Co-doped Hydroxyapatite as Magnetic, Up-conversion and Down-conversion Materials for Multimodal Imaging. Sci. Rep. 2019. 9(1): 16305. https://doi.org/10.1038/s41598-019-52885-0
46. Kusyak A.P., Petranovska A.L., Turanska S.P., Oranska O.I., Shuba Ya.M., Kravchuk D.I., Kravchuk L.I., Nazarenko V.G., Kravchuk R.M., Dubok V.A., Chornyi V.S., Bur'yanov O.A., Sobolevs'kyy Yu.L., Gorbyk P.P. Synthesis, Properties and Application Possibilities of X-ray Luminescent Nanocrystalline Lanthanum Phosphate. Chemistry, Physics and Technology of Surface. 2022. 13(4): 425.
47. Kusyak A.P., Petranovska A.L., Oranska O.I., Turanska S.P., Shuba Ya.M., Kravchuk D.I., Kravchuk L.I., Sotkis G.V., Nazarenko V.G., Kravchuk R.M., Dubok V.A., Bur'yanov O.A., Chornyi V.S., Sobolevs'kyy Yu.L., Gorbyk P.P. X-ray Luminescent Nanostructures Based on Lanthanum Fluoride and Phosphate for Optopharmacology and Photodynamic Therapy of Tumor Diseases. Poverhnia. 2023. 15(30): 268. [in Ukrainian].
48. Kusyak A., Petranovska A., Shchehlov O., Kravchuk R., Shuba Ya., Gorbyk P. X-ray Luminescent Nanocomposite LaF3:Tb/Citr@[Ru(bpy)2(nic)2]2+ as a Model Targeted Delivery System for Photopharmacology and Photodynamic Therapy. Hybrid Advances. 2024. 5: 100154. https://doi.org/10.1016/j.hybadv.2024.100154
49. Lu Y.H., Xiao X.F., Zheng X. Wu S.S., Liu R.F. Hydrothermal Synthesis and Characterization of Tb3+ Doped Hydroxyapatite. Adv. Mater. Res. 2012. 391: 709. https://doi.org/10.4028/www.scientific.net/AMR.391-392.709
50. Bhattacharjee S. DLS and Zeta Potential - Why They Are and What They Are Not? J. Control. Release. 2016. 235(2016): 337. https://doi.org/10.1016/j.jconrel.2016.06.017
51. Han Y., Wang X., Dai H., Li S. Nanosize and Surface Charge Effects of Hydroxyapatite Nanoparticles on Red Blood Cell Suspensions. ACS Appl. Mater. Interfaces. 2012. 4(9): 4616. https://doi.org/10.1021/am300992x
52. Chen L., Mccrate J.M., Lee J.C-M., Li H. The Role of Surface Charge on the Uptake and Biocompatibility of Hydroxyapatite Nanoparticles with Osteoblast Cells. Nanotechnology. 2011. 22(10) 105708. https://doi.org/10.1088/0957-4484/22/10/105708
53. Turon P., Del Valle L.J., Alemán C., Puiggali J. Biodegradable and Biocompatible Systems Based on Hydroxyapatite Nanoparticles. Appl. Sci. 2017. 7(1): 60. https://doi.org/10.3390/app7010060
54. Wang C., Jeong K.-J., Kim J., Kang S.W., Kang J., Han I.H., Lee I.-W., Oh S.-J., Lee J. Emission-tunable Probes Using Terbium(III)-doped Self-activated Luminescent Hydroxyapatite for In Vitro. J. Colloid Interface Sci. 2021. 581(A): 21. https://doi.org/10.1016/j.jcis.2020.07.083
55. Yang C., Yang P., Wang W., Zhang M., Lin J. Solvothermal Synthesis and Characterization of Ln (Eu3+, Tb3+) Doped Hydroxyapatite. J. Colloid Interface Sci. 2008. 328(1): 203. https://doi.org/10.1016/j.jcis.2008.09.010
56. Venkatasubbu G.D., Ramasamy S., Ramakrishnan V., Kumar J. Nanocrystalline Hydroxyapatite and Zinc-doped Hydroxyapatite as Carrier Material for Controlled Delivery of Ciprofloxacin. 3 Biotech. 2011. 1(3): 173. https://doi.org/10.1007/s13205-011-0021-9
57. Koort J.K., Mäkinen T.J., Suokas E., Veiranto M., Jalava J., Törmälä P., Aro H.T. Sustained Release of Ciprofloxacin from an Osteoconductive Poly(DL)-lactide Implant. Acta Orthop. 2008. 79(2): 295. https://doi.org/10.1080/17453670710015111
58. Chaussemier M., Pourmohtasham E., Gelus D., Pécoul N., Perrot H., Lédion J., Cheap-Charpentier H., Horner O. State of Art of Natural Inhibitors of Calcium Carbonate Scaling. A Review Article. Desalination. 2015. 356: 47. https://doi.org/10.1016/j.desal.2014.10.014
59. Li J., Liu Y., Gao Y., Zhong L., Zou Q., Lai X. Preparation and Properties of Calcium Citrate Nanosheets for Bone Graft Substitute. Bioengineered. 2016. 7(5): 376. https://doi.org/10.1080/21655979.2016.1226656
60. Kolmas J., Marek D., Kolodziejski W. Near-Infrared (NIR) Spectroscopy of Synthetic Hydroxyapatites and Human Dental Tissues. Appl. Spectrosc. 2015. 69(8): 902. https://doi.org/10.1366/14-07720
61. Grabska J., Ishigaki M., Beć K.B., Wojcik M.J., Ozaki Y. Correlations between Structure and Near-Infrared Spectra of Saturated and Unsaturated Carboxylic Acids. Insight From Anharmonic Density Functional Theory Calculations. J. Phys. Chem. A. 2017. 121(18): 3437. https://doi.org/10.1021/acs.jpca.7b02053
62. Barbooti M.M., Al-Sammerrai D.A. Thermal Decomposition of Citric Acid. Termochim. Acta. 1986. 98: 119. https://doi.org/10.1016/0040-6031(86)87081-2
63. Mansour S.A.A. Thermal Decomposition of Calcium Citrate Tetrahydrate. Thermochim. Acta. 1994. 233: 243. https://doi.org/10.1016/0040-6031(94)85118-2
64. Sing K.S.W. Reporting Physisorption Data for Gas/solid Systems with Special Reference to the Determination of Surface Area and Aorosity (Recommendations 1984). Pure Appl. Chem. 1985. 57(4): 603. https://doi.org/10.1351/pac198557040603
65. Xia X., Chen J., Shen J., Huang D., Duan P., Zou G. Synthesis of Hollow Structural Hydroxyapatite with Different Morphologies Using Calcium Carbonate as Hard Template. Adv. Powder Technol. 2018. 29(7): 1562. https://doi.org/10.1016/j.apt.2018.03.021
66. Rhati H., Laghzizil A., Saoiabi A., El Asri S., Lahlil K., Gacoin T. Surface Properties of Porous Hydroxyapatite Derived from Natural Phosphate. Mater. Chem. Phys. 2012. 136(2-3): 1022. https://doi.org/10.1016/j.matchemphys.2012.08.042
67. Zhang Y., Shao D., Yan J., Jia X., Li Y., Yu P., Zhang T. The Pore Size Distribution and its Relationship with Shale Gas Capacity in Organic-rich Mudstone of Wufeng-Longmaxi Formations, Sichuan Basin, China. J. Nat. Gas Geosci. 2016. 1(3): 213. https://doi.org/10.1016/j.jnggs.2016.08.002
68. Chen Z., Liu Y., Mao L., Gong L., Sun W., Feng L. Effect of Cation Doping on the Structure of Hydroxyapatite and the Mechanism of Defluoridation. Ceram. Int. 2018. 44(6): 6002. https://doi.org/10.1016/j.ceramint.2017.12.191
69. Thommes M., Kaneko K., Neimark A.V., Olivier J.P., Rodriguez-Reinoso F., Rouquerol J., Sing K.S.W. Physisorption of Gases, with Special Reference to the Evaluation of Surface Area and Pore Size Distribution (IUPAC Technical Report). Pure Appl. Chem. 2015. 87(9-10): 1051. https://doi.org/10.1515/pac-2014-1117
DOI: https://doi.org/10.15407/hftp16.01.115
Copyright (©) 2025 O. D. Shchehlov, A. P. Kusyak, O. I. Oranska, R. M. Kravchuk, A. L. Petranovska, Ya. M. Shuba, P. P. Gorbyk


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