Fluorapatite Materials with Upconversion Fluorescence and Photothermal Conversion and Preparation Methods Thereof

Abstract

The present invention belongs to the fields of luminescent materials and biomedical materials, and provides a fluorapatite material with both upconversion fluorescence and photothermal conversion and a preparation method thereof. The preparation method includes the following steps: (1) Dissolve a Ca 2+ source, a Ln1 3+ source, and a Ln2 3+ source in deionized water to obtain solution A; dissolve a PO4 3‑ source, an F ‑ source, and a MoO4 2‑ source in deionized water to obtain solution B; (2) Drop solution B into solution A, and stir for 1-2 h after the dropping is completed to obtain a reaction precursor solution; (3) Perform a hydrothermal reaction on the reaction precursor solution; (4) Perform a thermal activation treatment on the obtained hydrothermal product; (5) Disperse the obtained activated powder in an aqueous solution of Fe 3+ , perform a hydrothermal reaction, wash, and dry to obtain the product. The present invention can endow an upconversion fluorescent material with good photothermal conversion performance without compounding a photothermal conversion agent, and simplifies the preparation method of a material with both upconversion fluorescence and photothermal conversion performance.

Description

Technical Field

[0001] The present invention belongs to the fields of luminescent materials and biomedical materials, and relates to fluorapatite materials with upconversion fluorescence and photothermal conversion and a preparation method thereof. Background Art

[0002] Hydroxyapatite (HAp) crystals are the main inorganic components in human bone and dental tissues, have good biocompatibility with cells and tissues, and can be used as biomaterials. The hydroxyl groups in hydroxyapatite can undergo an ion exchange reaction with fluoride ions, causing the hydroxyl groups of hydroxyapatite to be replaced by fluoride ions to obtain fluorapatite (FAp). The phonon energy of fluoride ions in fluorapatite is smaller and it has better antibacterial ability, and it can be used as a rare-earth ion-doped apatite biomaterial with good fluorescence performance. Incorporating specific rare-earth elements into apatite crystals can endow the apatite materials with upconversion fluorescence properties, and incorporating molybdate ions into apatite crystals can further improve the upconversion fluorescence intensity of apatite. At present, the excitation light of materials such as hydroxyapatite or fluorapatite with upconversion fluorescence characteristics is near-infrared light. Near-infrared light has better tissue penetration ability compared with visible light and ultraviolet light. Therefore, such materials have been proven to have good in vivo tracing performance.

[0003] Photothermal conversion materials can absorb excitation light of a specific wavelength and generate heat through photothermal conversion. Photothermal therapy has been applied in the fields of antibacterial and anti-tumor in the field of biomaterials. Biomaterials with both upconversion fluorescence and photothermal conversion capabilities can simultaneously achieve the dual effects of in vivo material tracing and photothermal therapy. However, directly using upconversion materials for photothermal conversion often results in poor photothermal conversion performance (see Zhao, X., Suo, H., Zhang, Z., Guo, C. (2019).Upconverting CeO2: Yb 3+ / Tm 3+ hollow nanospheres for photo-thermal sterilizationand deep-tissue imaging in the first biological window. Ceramics International , 45(17), 21910 - 21916), while to achieve a high photothermal conversion efficiency, it is usually necessary to compound photothermal conversion agents such as dopamine and carbon materials outside the upconversion material. However, the preparation process of the material is complex (see Zhu, X., Feng, W., Chang, J., Tan, Y. W., Li, J., Chen, M., Sun, Y., Li, F. (2016). Temperature - feedback upconversion nanocomposite for accurate photothermal therapy at facile temperature. Nature communications , 7 (1), 1 - 10., Gu, M., Zhang, L., Hao, L., Wang, K., Yang, W., Liu, Z., Lei, Z., Zhang, Y., Li, W., Jiang, L., Li, X. (2023). Upconversion Nanoplatform Enables Multimodal Imaging and Combinatorial Immunotherapy for Synergistic Tumor Treatment and Monitoring. ACS Applied Materials&Interfaces , 15 (18), 21766 - 21780). Summary of the Invention

[0004] Aiming at the problems that the existing upconversion materials have poor photothermal conversion performance and need to compound photothermal conversion agents such as dopamine and carbon materials outside the upconversion material to effectively enhance the photothermal conversion performance of the material, resulting in a complex material preparation process, etc., the present invention provides a fluorapatite material with both upconversion fluorescence and photothermal conversion and its preparation method, so as to endow the upconversion fluorescent material with good photothermal conversion performance without compounding photothermal conversion agents and simplify the preparation method of the material with both upconversion fluorescence and photothermal conversion performance.

[0005] To achieve the above - mentioned invention purpose, the technical solution adopted by the present invention is as follows:

[0006] A preparation method of a fluorapatite material with both upconversion fluorescence and photothermal conversion, comprising the following steps:

[0007] (1) Dissolve the Ca 2+ source, Ln1 3+ source, Ln2 3+ source in deionized water to obtain solution A; in solution A, Ln13+ , Ln2 3+ and Ca 2+ have a molar ratio of (5 - 20) : (0.05 - 2) : (78 - 94.95); Ln1 3+ and Ln2 3+ are different rare earth ions;

[0008] Dissolve the PO4 3- source, F - source and MoO4 2- source in deionized water to obtain solution B; in solution B, the molar ratio of P to Mo is (80 - 92) : (8 - 20), and the ratio of the sum of the molar amounts of P and Mo to the molar amount of F is 3 : 1;

[0009] (2) Under the conditions of 20 - 80 °C and stirring, add solution B dropwise to solution A, and control the pH value of the resulting mixture to be between 9 and 10 during the dropping process. After the dropping is completed, continue stirring for 1 - 2 h to obtain a reaction precursor solution; control the ratio of the sum of the molar amounts of Ca, Ln1, and Ln2 in the reaction precursor solution to the sum of the molar amounts of P and Mo to be 5 : 3;

[0010] (3) Carry out a hydrothermal reaction on the reaction precursor solution at 120 - 200 °C, collect the precipitate obtained from the reaction, wash it, and dry it to obtain a hydrothermal product;

[0011] (4) Carry out a thermal activation treatment on the hydrothermal product in an air atmosphere at 600 - 1000 °C to obtain an activated powder;

[0012] (5) Disperse the activated powder sufficiently in an aqueous solution of Fe 3+ , carry out a hydrothermal reaction at 120 - 200 °C, collect the precipitate obtained from the reaction, wash it, and dry it to obtain a fluorapatite material with both up - conversion fluorescence and photothermal conversion.

[0013] In the technical solution of the above preparation method, the Ln1 3+ is Yb 3+ , and the Ln2 3+ is at least one of Ho 3+ , Er 3+ , Tm 3+ , Nd 3+ , Dy 3 + , Pr 3+ , Eu 3+ , Tb 3+ , Sm 3+ , Ce 3+ .

[0014] In the technical solution of the above preparation method, Ca in solution A 2+The concentration of 3- is 10 - 2000 mmol / L, preferably 15 - 160 mmol / L, and the concentration of PO4 in solution B

[0015] In step (5) of the technical solution of the above preparation method, the concentration of Fe in the aqueous solution of Fe 3+ is preferably 0.1 - 10 mmol / L, and the mass ratio of the activated powder to the aqueous solution of Fe 3+ is preferably controlled to be 1:(10 - 100). 3+

[0016] In step (3) of the technical solution of the above preparation method, the hydrothermal reaction time is preferably controlled to be 4 - 24 h.

[0017] In step (5) of the technical solution of the above preparation method, the hydrothermal reaction time is preferably controlled to be 1 - 24 h.

[0018] In step (4) of the technical solution of the above preparation method, the thermal activation treatment time is preferably controlled to be 1 - 4 h.

[0019] In the technical solution of the above preparation method, the Ca 2+ source is a water-soluble salt of Ca 2+ , for example, the Ca 2+ source can be calcium nitrate, calcium chloride or calcium acetate; the Ln1 3+ source is a water-soluble salt of Ln1 3+ , for example, the Ln1 3+ source can be nitrate, hydrochloride, acetate or sulfate of Ln1 3+ ; the Ln2 3+ source is a water-soluble salt of Ln2 3+ , for example, the Ln2 3+ source can be nitrate, hydrochloride, acetate or sulfate of Ln2 3+ ; the PO4 3- source is trisodium phosphate, diammonium hydrogen phosphate or ammonium dihydrogen phosphate; the F - source is sodium fluoride or ammonium fluoride; the MoO4 2- source is ammonium molybdate or ammonium heptamolybdate.

[0020] In the technical solution of the above preparation method, the aqueous solution of Fe 3+ is prepared by dissolving the water-soluble salt of Fe 3+ in water, and the water-soluble salt of Fe 3+ can be ferric nitrate, ferric chloride, ferric acetate or ferric sulfate.

[0021] ​The present invention also provides a fluoroapatite material having both upconversion fluorescence and photothermal conversion prepared by the above method, wherein the multi-ion doped fluoroapatite material is obtained by first replacing part of the lattice calcium ions and phosphate groups in the fluoroapatite with rare earth ions and molybdate ions, and then replacing part of the calcium ions and / or rare earth ions on the surface of the obtained material with iron ions. The multi-ion doped fluoroapatite material can emit fluorescence visible to the human eye under the excitation of near-infrared light with a wavelength of 980 nm, and at the same time has excellent photothermal energy conversion performance imparted by iron ions.

[0022] Compared with the prior art, the technical solution provided by the present invention produces the following beneficial technical effects:

[0023] 1. The present invention provides a method for preparing a fluoroapatite material having both upconversion fluorescence and photothermal conversion. The method first prepares fluoroapatite co-doped with rare earth ions and molybdate ions, then heat-treats the fluoroapatite to obtain an activated powder having upconversion fluorescence, and then disperses the activated powder in Fe 3+ The aqueous solution of Fe 3+ It is obtained by replacing part of the calcium ions and / or rare earth ions on the surface of the activated powder. The method of the present invention mainly enhances the non-radiative energy transfer of the material by introducing iron ions on the surface of the multi-ion-doped fluoroapatite material with strong up-conversion fluorescence, and gives the material good photothermal conversion performance on the basis of strong up-conversion fluorescence performance. Compared with the prior art method of strengthening the photothermal conversion performance of the up-conversion material by compounding photothermal conversion agents such as dopamine and carbon materials outside the up-conversion material, the method of the present invention is based on a simple hydrothermal synthesis technology, that is, it realizes the preparation of materials with both strong up-conversion fluorescence and photothermal conversion functions, and has the characteristics of low production cost, economy, environmental protection, and convenience for industrial production.

[0024] 2. Fluorapatite materials and rare earth-doped fluoroapatite materials have good osteogenic biological activity, are similar to the chemical properties of autologous bone minerals, can promote the repair of bone tissue, and have important application prospects in the medical field. The present invention endows the fluoroapatite material with strong upconversion fluorescence performance and excellent photothermal conversion performance. The material prepared by the present invention has a high upconversion emission efficiency under the excitation of near-infrared light with a wavelength of 980 nm. Under the excitation of near-infrared light, the material located in the deep tissue can be efficiently excited and traced, thereby avoiding the problem of shallow tissue penetration depth and tissue damage caused by ultraviolet and visible light excitation. At the same time, the photothermal conversion performance of the material enables it to realize photothermal therapy on the basis of in vivo tissue repair and material tracing. The above characteristics can effectively expand the application of existing fluoroapatite materials and rare earth-doped fluoroapatite materials in basic biomedical research, in vivo tracing of biomaterials, tissue repair, and photothermal therapy.

[0025] 3. The present invention has been confirmed by experiments that, compared with the existing doped hydroxyapatite powder with upconversion fluorescence properties, the photothermal conversion performance of the fluorapatite material with both upconversion fluorescence and photothermal conversion prepared by the method of the present invention has been significantly improved. When irradiated with near-infrared light at a wavelength of 980 nm with the same power for 25 s, the temperature rise of the fluorapatite material with both upconversion fluorescence and photothermal conversion of the present invention can reach 70 °C, while the temperature rise of the existing doped hydroxyapatite powder with upconversion fluorescence properties is only about 15 °C. The photothermal conversion efficiency of the fluorapatite material with both upconversion fluorescence and photothermal conversion prepared by the method of the present invention is significantly higher.

[0026] 4. The present invention has been confirmed by experiments that when the fluorapatite material with both upconversion fluorescence and photothermal conversion prepared by the method of the present invention is placed under the pig skin and excited with near-infrared light at a wavelength of 980 nm and observed under a two-photon microscope, it is found that under the excitation of near-infrared light, the fluorapatite material with both upconversion fluorescence and photothermal conversion of the present invention can still emit strong green upconversion fluorescence in the tissue, and is not interfered by the autofluorescence of the tissue, and can distinguish the material from the autologous tissue in vivo. The upconversion fluorescence performance of the fluorapatite material with both upconversion fluorescence and photothermal conversion can meet the intensity requirements for fluorescence tracing of the material in vivo in practical applications. Description of the Drawings

[0027] Figure 1 is the scanning electron microscope image of FYEM / Fe.

[0028] Figure 2 is the XPS spectrum of FYEM / Fe, where (a) is the total XPS spectrum and (b) is the Fe 2p sub-spectrum.

[0029] Figure 3 is the XRD spectra of FYEM / Fe and FYEM, where ICDD: 15-0876 is the XRD spectrum of the fluorapatite standard card, and ICDD: 29-0351 is the XRD spectrum of the calcium molybdate standard card.

[0030] Figure 4 is the UV-Vis-NIR diffuse reflectance absorption spectra of FYEM / Fe and FYEM.

[0031] Figure 5 is the upconversion fluorescence emission spectra of FYEM / Fe and FYEM.

[0032] Figure 6 Figure (a) is the bright-field photo under a stereomicroscope when the powdered FYEM / Fe is placed under 6 mm thick pig skin. Figure 6Figure (b) is a dark-field photograph under a stereomicroscope when excited by near-infrared light with a wavelength of 980 nm in vivo.

[0033] Figure 7 are the heating curves plotted from the readings of an infrared thermal imager when FYTM / Fe, FYEM / Fe, FYEM, and FYH / Fe are excited by near-infrared light with a wavelength of 980 nm. Detailed implementation mode

[0034] The following further illustrates the fluorapatite material with upconversion fluorescence and photothermal conversion and its preparation method according to the present invention through examples. It is necessary to point out that the following examples are only used to further illustrate the present invention and cannot be construed as limiting the protection scope of the present invention. Those skilled in the art make some non-essential improvements and adjustments to the present invention based on the above invention content for specific implementation, which still fall within the protection scope of the present invention.

[0035] Example 1

[0036] In this example, the preparation of the fluorapatite material with upconversion fluorescence and photothermal conversion is carried out as follows:

[0037] (1) Dissolve calcium nitrate, ytterbium nitrate, and thulium nitrate in deionized water to obtain solution A; in solution A, the molar ratio of Yb 3+ , Tm 3+ to Ca 2+ is 20:0.1:79.9, and the concentration of calcium nitrate is 15.98 mmol / L.

[0038] Dissolve diammonium hydrogen phosphate, sodium fluoride, and ammonium heptamolybdate in deionized water to obtain solution B; in solution B, the molar ratio of P to Mo is 92:8, and the molar ratio of the sum of the molar amounts of P and Mo (P + Mo) to F is 3:1; the concentration of diammonium hydrogen phosphate is 11.04 mmol / L.

[0039] (2) Dropwise add solution B to solution A at 25 °C under stirring conditions, and control the pH value of the obtained mixed solution to 9 by adding sodium hydroxide solution during the dropping process. After the dropping is completed, continue stirring for 1 h to obtain a reaction precursor solution. Control the dropping amount of solution B so that the ratio of the sum of the molar amounts of Ca, Yb, and Tm (Ca + Yb + Tm) to the sum of the molar amounts of P and Mo (P + Mo) in the reaction precursor solution is 5:3.

[0040] (3) Hydrothermally react the reaction precursor solution obtained in step (2) at 180 °C for 6 h, filter, collect the reaction precipitate, wash it 3 times with deionized water and anhydrous ethanol respectively, and freeze-dry to obtain a hydrothermal product.

[0041] (4) The hydrothermal product obtained in step (3) was thermally activated in an air atmosphere at 900 °C for 2 h to obtain an activated powder with upconversion fluorescence, denoted as FYTM.

[0042] (5) FYTM was added to an aqueous solution of iron nitrate with a concentration of 2 mmol / L. The mass ratio of FYTM to the aqueous solution of iron nitrate was controlled to be 1:50. After stirring well, a hydrothermal reaction was carried out at 180 °C for 6 h, so that some calcium ions and / or rare earth ions on the surface of FYTM were replaced by iron ions. After filtration, the precipitate obtained from the reaction was collected and washed 3 times with deionized water and anhydrous ethanol respectively, and then freeze-dried to obtain a fluorapatite material FAp: Yb / Tm / Mo / Fe with both upconversion fluorescence and photothermal conversion, abbreviated as FYTM / Fe.

[0043] Comparative Example 1

[0044] In this comparative example, a multi-ion doped fluorapatite material with upconversion fluorescence performance was prepared, and the steps were as follows:

[0045] (1) Calcium nitrate, ytterbium nitrate, and thulium nitrate were dissolved in deionized water to obtain solution A; in solution A, the molar ratio of Ln1 3+ , Ln2 3+ to Ca 2+ was 20:0.1:79.9, and the concentration of calcium nitrate was 15.98 mmol / L.

[0046] Ammonium hydrogen phosphate, sodium fluoride, and ammonium heptamolybdate were dissolved in deionized water to obtain solution B; in solution B, the molar ratio of P to Mo was 92:8, and the ratio of the sum of the molar amounts of P and Mo (P + Mo) to the molar amount of F was 3:1; the concentration of ammonium hydrogen phosphate was 11.04 mmol / L.

[0047] (2) Under the conditions of 25 °C and stirring, solution B was gradually added dropwise to solution A. During the dropping process, the pH value of the obtained mixed solution was controlled to be 9 by adding sodium hydroxide solution. After the dropping was completed, stirring was continued for 1 h to obtain a reaction precursor solution. The dropping amount of solution B was controlled so that the ratio of the sum of the molar amounts of Ca, Yb, and Tm (Ca + Yb + Tm) to the sum of the molar amounts of P and Mo (P + Mo) in the reaction precursor solution was 5:3.

[0048] (3) The reaction precursor solution obtained in step (2) was subjected to a hydrothermal reaction at 180 °C for 6 h, filtered, the precipitate obtained from the reaction was collected, washed 3 times with deionized water and anhydrous ethanol respectively, and then freeze-dried to obtain a hydrothermal product.

[0049] (4) The hydrothermal product obtained in step (3) was thermally activated in an air atmosphere at 900 °C for 2 h to obtain an activated powder with upconversion fluorescence, denoted as FYTM. This FYTM is a multi-ion doped fluorapatite material with upconversion fluorescence properties.

[0050] Example 2

[0051] In this example, a fluorapatite material with both upconversion fluorescence and photothermal conversion was prepared as follows:

[0052] (1) Calcium nitrate, ytterbium nitrate, and erbium nitrate were dissolved in deionized water to obtain solution A; in solution A, the molar ratio of Yb 3+ , Er 3+ to Ca 2+ was 10:0.5:89.5, and the concentration of calcium nitrate was 17.9 mmol / L.

[0053] Ammonium dihydrogen phosphate, sodium fluoride, and ammonium heptamolybdate were dissolved in deionized water to obtain solution B; in solution B, the molar ratio of P to Mo was 85:15, and the ratio of the sum of the molar amounts of P and Mo (P + Mo) to the molar amount of F was 3:1; the concentration of ammonium dihydrogen phosphate was 10.2 mmol / L.

[0054] (2) At 25 °C and under stirring conditions, solution B was gradually added dropwise to solution A. During the dropping process, the pH value of the resulting mixture was controlled to 9 by adding sodium hydroxide solution. After the dropping was completed, stirring was continued for 1 h to obtain a reaction precursor solution. The dropping amount of solution B was controlled so that the ratio of the sum of the molar amounts of Ca, Yb, and Er (Ca + Yb + Er) to the sum of the molar amounts of P and Mo (P + Mo) in the reaction precursor solution was 5:3.

[0055] (3) The reaction precursor solution obtained in step (2) was subjected to hydrothermal reaction at 180 °C for 6 h, filtered, and the reaction precipitate obtained was collected. It was washed 3 times with deionized water and anhydrous ethanol respectively, and freeze-dried to obtain a hydrothermal product.

[0056] (4) The hydrothermal product obtained in step (3) was thermally activated in an air atmosphere at 900 °C for 2 h to obtain an activated powder with upconversion fluorescence, denoted as FYEM.

[0057] (5) FYEM was added to an aqueous solution of iron nitrate with a concentration of 2 mmol / L, and the mass ratio of FYEM to the aqueous solution of iron nitrate was controlled to be 1:50. After stirring evenly, a hydrothermal reaction was carried out at 180 °C for 6 h, so that part of the calcium ions and / or rare earth ions on the surface of FYEM were replaced by iron ions. After filtration, the precipitate obtained from the reaction was collected, washed 3 times with deionized water and anhydrous ethanol respectively, and freeze-dried to obtain the fluorapatite material FAp: Yb / Er / Mo / Fe with upconversion fluorescence and photothermal conversion, abbreviated as FYEM / Fe.

[0058] The scanning electron microscope (SEM) image of the FYEM / Fe prepared in this example is as Figure 1 shown. It can be seen from Figure 1 that the microstructure of the FYEM / Fe prepared in this example is a nanorod and nanosphere-like structure.

[0059] X-ray photoelectron spectroscopy (XPS) analysis was carried out on the FYEM / Fe prepared in this example, and the results are as Figure 2 shown. Among them, Figure (a) is the total XPS spectrum, and Figure (b) is the Fe 2p partial spectrum. It can be seen from Figure 2 that the incorporated +3-valent Yb element, +3-valent Er element, +6-valent molybdenum element and +3-valent Fe element were detected in FYEM / Fe, indicating that Yb 3+ , Er 3+ , MoO4 2- were successfully incorporated into the fluorapatite, and Fe 3+ was also successfully replaced on the surface of FYEM. Inductively coupled plasma mass spectrometry (ICP-MS) analysis was carried out on the FYEM / Fe prepared in this example, and the relative atomic contents of each element in FYEM / Fe were measured as shown in Table 1. It can be seen from Table 1 that the atomic content of iron element in the FYEM / Fe prepared in this example is 6.24%.

[0060] Table 1 Relative atomic contents of each element in FYEM / Fe

[0061] Element Relative atomic content (%) Ca 12.33 Yb 3.30 Er 0.13 Fe 6.24 P 11.92 Mo 2.70 O 58.50

[0062] Comparative Example 2

[0063] In this comparative example, a multi-ion doped fluorapatite material with upconversion fluorescence performance was prepared, and the steps are as follows:

[0064] (1) Calcium nitrate, ytterbium nitrate and erbium nitrate were dissolved in deionized water to obtain solution A; in solution A, the molar ratio of Yb 3+ , Er 3+ to Ca 2+ was 10:0.5:89.5, and the concentration of calcium nitrate was 17.9 mmol / L.

[0065] Dissolve diammonium hydrogen phosphate, sodium fluoride and ammonium heptamolybdate in deionized water to obtain solution B; in solution B, the molar ratio of P to Mo is 85:15, and the molar ratio of the sum of the molar amounts of P and Mo (P + Mo) to the molar amount of F is 3:1; the concentration of diammonium hydrogen phosphate is 10.2 mol / L.

[0066] (2) Dropwise add solution B to solution A at 25 °C under stirring conditions. During the dropping process, control the pH value of the resulting mixed solution to 9 by adding sodium hydroxide solution. After the dropping is completed, continue stirring for 1 h to obtain a reaction precursor solution. Control the dropping amount of solution B so that the ratio of the sum of the molar amounts of Ca, Yb and Er (Ca + Yb + Er) to the sum of the molar amounts of P and Mo (P + Mo) in the reaction precursor solution is 5:3.

[0067] (3) Hydrothermally react the reaction precursor solution obtained in step (2) at 180 °C for 6 h, filter, collect the precipitate obtained from the reaction, wash it 3 times with deionized water and anhydrous ethanol respectively, and freeze-dry to obtain a hydrothermal product.

[0068] (4) Thermally activate the hydrothermal product obtained in step (3) in an air atmosphere at 900 °C for 2 h to obtain an activated powder with upconversion fluorescence, denoted as FYEM. This FYEM is a multi-ion doped fluorapatite material with upconversion fluorescence properties.

[0069] Comparative Example 3

[0070] In this example, to prepare a fluorapatite material with both upconversion fluorescence and photothermal conversion, the steps are as follows:

[0071] (1) Dissolve calcium nitrate, ytterbium nitrate and holmium nitrate in deionized water to obtain solution A; in solution A, the molar ratio of Yb 3+ , Ho 3+ to Ca 2+ is 10:0.1:89.9, and the concentration of calcium nitrate is 17.18 mmol / L.

[0072] Dissolve diammonium hydrogen phosphate and sodium fluoride in deionized water to obtain solution B; in solution B, the molar ratio of P to F is 3:1; the concentration of diammonium hydrogen phosphate is 10.2 mmol / L.

[0073] (2) Dropwise add solution B to solution A at 25 °C under stirring conditions. During the dropping process, control the pH value of the resulting mixed solution to 9 by adding sodium hydroxide solution. After the dropping is completed, continue stirring for 1 h to obtain a reaction precursor solution. Control the dropping amount of solution B so that the ratio of the sum of the molar amounts of Ca, Yb and Ho (Ca + Yb + Ho) to the molar amount of P in the reaction precursor solution is 5:3.

[0074] (3) Hydrothermally react the reaction precursor solution obtained in step (2) at 180 °C for 6 h, filter, collect the precipitate obtained from the reaction, wash it three times with deionized water and anhydrous ethanol respectively, and freeze-dry to obtain a hydrothermal product.

[0075] (4) Activate the hydrothermal product in an air atmosphere at 900 °C for 2 h to obtain a thermally activated powder, denoted as FYH.

[0076] (5) Add FYH to an aqueous solution of iron nitrate with a concentration of 2 mmol / L, control the mass ratio of FYH to the aqueous solution of iron nitrate to be 1:50, stir well, hydrothermally react at 180 °C for 6 h, so that some calcium ions and / or rare earth ions on the surface of FYH are replaced by iron ions, filter, collect the precipitate obtained from the reaction, wash it three times with deionized water and anhydrous ethanol respectively, and freeze-dry to obtain the fluorapatite material FAp: Yb / Ho / Fe with both upconversion fluorescence and photothermal conversion, abbreviated as FYH / Fe.

[0077] Perform X-ray diffraction (XRD) analysis on FYEM / Fe prepared in Example 2 and FYEM prepared in Comparative Example 2. The results are as Figure 3 shown. It can be Figure 3 seen that the diffraction peaks of FYEM / Fe prepared in Example 2 and FYEM prepared in Comparative Example 2 are basically consistent with the standard card of fluorapatite (FAp) (ICDD: 15-0876), and a certain degree of CaMoO4 (ICDD: 29-0351) impurity phase appears, indicating that the incorporation of rare earth ions Yb 3+ 、Er 3+ and Fe 3+ does not significantly change the FAp crystal structure, while the incorporation of MoO4 2- will lead to the appearance of CaMoO4 impurity phase in the FAp crystal.

[0078] Perform ultraviolet-visible-near-infrared diffuse reflectance (UV-Vis-NIR DRS) analysis on FYEM / Fe prepared in Example 2 and FYEM prepared in Comparative Example 2 to investigate the absorbance change of the material in the ultraviolet-visible-near-infrared region after co-doping. The results are as Figure 4 shown. It can be Figure 4 seen that compared with FYEM prepared in Comparative Example 2, the absorbance value of FYEM / Fe prepared in Example 2 in the visible light region is significantly higher, indicating that after the incorporation of iron ions, the electrons in the high energy levels of lanthanide ions can interact with the energy levels of iron ions through non-radiative energy transfer.

[0079] The near-infrared light with a wavelength of 980 nm was used to excite FYEM / Fe prepared in Example 2 and FYEM prepared in Comparative Example 2, and the upconversion fluorescence emission spectra of each sample were tested to investigate the change in the upconversion fluorescence performance of the material after co-doping. The results are as Figure 5 shown. As Figure 5 can be seen, under the excitation of the near-infrared light with a wavelength of 980 nm, compared with FYEM prepared in Comparative Example 2, the upconversion fluorescence intensity of FYEM / Fe prepared in Example 2 decreased in the visible light region, and the fluorescence intensity decreased by about 90% in the green light region. This is mainly due to the enhanced non-radiative energy transfer caused by the introduction of iron ions. The powdered FYEM / Fe prepared in Example 2 was placed under the 6-mm-thick pig skin, excited from above the pig skin with the near-infrared light with a wavelength of 980 nm, and observed under a stereomicroscope to investigate the in-vivo fluorescence tracing performance of FYEM / Fe prepared in Example 2. The results are as Figure 6 shown. Figure (a) therein is the bright-field photo under the stereomicroscope with the powdered FYEM / Fe placed under the 6-mm-thick pig skin, and figure (b) therein is the dark-field photo when excited with the near-infrared light with a wavelength of 980 nm under the stereomicroscope. As Figure 6 can be seen, under the excitation of the near-infrared light with a wavelength of 980 nm, FYEM / Fe prepared in Example 2 can still emit strong green upconversion fluorescence in the tissue, and is not interfered by the autofluorescence of the tissue, and the FYEM / Fe material can be distinguished from the tissue in vivo. Generally speaking, although the upconversion fluorescence intensity of the obtained FYEM / Fe decreased in the visible light region after the introduction of iron ions, its upconversion fluorescence performance can still meet the requirements for fluorescence tracing of materials in vivo in practical applications.

[0080] FYTM / Fe prepared in Example 1, FYEM / Fe prepared in Example 2, FYEM prepared in Comparative Example 2, and FYH / Fe prepared in Comparative Example 3 were irradiated with the near-infrared light with a wavelength of 980 nm at the same power for 25 s, and the infrared thermal imaging images of each sample were tested to investigate the change in the photothermal performance of the material after co-doping. The results are as Figure 7 shown. As Figure 7 can be seen: under the excitation of the near-infrared light with a wavelength of 980 nm, the temperature increase range of FYEM / Fe prepared in Example 2 is greater than that of FYEM prepared in Comparative Example 2, because part of the energy of the upconversion fluorescence is transferred to Fe on the surface of FYEM / Fe 3+, heat is generated through photothermal conversion during the non-radiative energy transfer process; meanwhile, the temperature increase of FYEM / Fe prepared in Example 2 is higher than that of FYTM / Fe prepared in Example 1, and the temperature increases of FYTM / Fe and FYEM / Fe are higher than that of FYH / Fe prepared in Comparative Example 3. That is, the photothermal conversion efficiencies of FYTM / Fe prepared in Example 1 and FYEM / Fe prepared in Example 2 are both significantly higher than that of FYH / Fe prepared in Comparative Example 3. This is because the upconversion fluorescence intensity of FYEM is better than that of FYTM, and the upconversion fluorescence intensity of FYTM is better than that of FYH / Fe without doped molybdate. This shows that the photothermal conversion performance of the material is positively correlated with the intensity of the upconversion fluorescence of the material. The stronger the upconversion fluorescence intensity of the material, the stronger its photothermal conversion performance after the hydrothermal reaction with iron ions.

[0081] Example 3

[0082] In this example, the preparation of the fluorapatite material with both upconversion fluorescence and photothermal conversion is as follows:

[0083] (1) Dissolve calcium nitrate, ytterbium nitrate, and holmium nitrate in deionized water to obtain Solution A; in Solution A, the molar ratio of Yb 3+ , Ho 3+ to Ca 2+ is 10:0.1:89.9, and the concentration of calcium nitrate is 17.18 mmol / L.

[0084] Dissolve diammonium hydrogen phosphate, sodium fluoride, and ammonium heptamolybdate in deionized water to obtain Solution B; in Solution B, the molar ratio of P to Mo is 80:20, and the ratio of the sum of the molar amounts of P and Mo (P + Mo) to the molar amount of F is 3:1; the concentration of diammonium hydrogen phosphate is 9.6 mmol / L.

[0085] (2) Dropwise add Solution B to Solution A at 25 °C under stirring conditions, and control the pH value of the resulting mixed solution to 9 by adding sodium hydroxide solution during the dropping process. After the dropping is completed, continue stirring for 1 h to obtain a reaction precursor solution. Control the dropping amount of Solution B so that the ratio of the sum of the molar amounts of Ca, Yb, and Ho (Ca + Yb + Ho) to the sum of the molar amounts of P and Mo (P + Mo) in the reaction precursor solution is 5:3.

[0086] (3) Hydrothermally react the reaction precursor solution obtained in step (2) at 180 °C for 6 h, filter, collect the precipitate obtained from the reaction, wash it 3 times with deionized water and anhydrous ethanol respectively, and freeze-dry to obtain a hydrothermal product.

[0087] (4) Thermally activate the hydrothermal product obtained in step (3) in an air atmosphere at 900 °C for 2 h to obtain an activated powder with upconversion fluorescence, denoted as FYHM.

[0088] (5) Add FYHM to an aqueous solution of iron nitrate with a concentration of 0.1 mmol / L, control the mass ratio of FYHM to the aqueous solution of iron nitrate to be 1:100, stir well, conduct a hydrothermal reaction at 180 °C for 6 h, so that part of the calcium ions and / or rare earth ions on the surface of FYHM are replaced by iron ions, filter, collect the precipitate obtained from the reaction, wash it three times with deionized water and absolute ethanol respectively, and freeze-dry to obtain the fluorapatite material FAp: Yb / Ho / Mo / Fe with both upconversion fluorescence and photothermal conversion, abbreviated as FYHM / Fe.

[0089] Example 4

[0090] In this example, the steps for preparing the fluorapatite material with both upconversion fluorescence and photothermal conversion are as follows:

[0091] (1) Dissolve calcium nitrate, ytterbium nitrate, and praseodymium nitrate in deionized water to obtain solution A; in solution A, the molar ratio of Yb 3+ , Pr 3+ to Ca 2+ is 5:0.05:94.95, and the concentration of calcium nitrate is 18.99 mmol / L.

[0092] Dissolve diammonium hydrogen phosphate, ammonium fluoride, and ammonium molybdate in deionized water to obtain solution B; in solution B, the molar ratio of P to Mo is 80:20, and the ratio of the sum of the molar amounts of P and Mo (P + Mo) to the molar amount of F is 3:1; the concentration of diammonium hydrogen phosphate is 9.6 mmol / L.

[0093] (2) Dropwise add solution B to solution A at 20 °C under stirring conditions. During the dropping process, control the pH value of the resulting mixture to be 10 by adding sodium hydroxide solution. After the dropping is completed, continue stirring for 2 h to obtain a reaction precursor solution. Control the dropping amount of solution B so that the ratio of the sum of the molar amounts of Ca, Yb, and Pr (Ca + Yb + Pr) to the sum of the molar amounts of P and Mo (P + Mo) in the reaction precursor solution is 5:3.

[0094] (3) Hydrothermally react the reaction precursor solution obtained in step (2) at 120 °C for 24 h, filter, collect the precipitate obtained from the reaction, wash it three times with deionized water and absolute ethanol respectively, and freeze-dry to obtain a hydrothermal product.

[0095] (4) Thermally activate the hydrothermal product obtained in step (3) in an air atmosphere at 1000 °C for 1 h to obtain an activated powder with upconversion fluorescence, denoted as FYPM.

[0096] (5) Add FYPM to an aqueous solution of iron nitrate with a concentration of 10 mmol / L, control the mass ratio of FYPM to the aqueous solution of iron nitrate to be 1:10, stir well, carry out a hydrothermal reaction at 120 °C for 24 h, so that part of the calcium ions and / or rare earth ions on the surface of FYPM are replaced by iron ions, filter, collect the precipitate obtained from the reaction, wash it 3 times with deionized water and absolute ethanol respectively, and freeze-dry to obtain the fluorapatite material FAp: Yb / Pr / Mo / Fe with both upconversion fluorescence and photothermal conversion, abbreviated as FYPM / Fe.

[0097] Example 5

[0098] In this example, the preparation of the fluorapatite material with both upconversion fluorescence and photothermal conversion is as follows:

[0099] (1) Dissolve calcium nitrate, ytterbium nitrate, and europium nitrate in deionized water to obtain solution A; in solution A, the molar ratio of Yb 3+ , Eu 3+ to Ca 2+ is 20:2:78, and the concentration of calcium nitrate is 156 mmol / L.

[0100] Dissolve trisodium phosphate, sodium fluoride, and ammonium heptamolybdate in deionized water to obtain solution B; in solution B, the molar ratio of P to Mo is 90:10, and the ratio of the sum of the molar amounts of P and Mo (P + Mo) to the molar amount of F is 3:1; the concentration of trisodium phosphate is 108 mmol / L.

[0101] (2) Dropwise add solution B to solution A at 80 °C under stirring conditions, control the pH value of the resulting mixture to be 9 by adding sodium hydroxide solution during the dropping process, continue stirring for 1 h after the dropping is completed to obtain a reaction precursor solution. Control the dropping amount of solution B so that the ratio of the sum of the molar amounts of Ca, Yb, and Eu (Ca + Yb + Eu) to the sum of the molar amounts of P and Mo (P + Mo) in the reaction precursor solution is 5:3.

[0102] (3) Hydrothermally react the reaction precursor solution obtained in step (2) at 200 °C for 4 h, filter, collect the precipitate obtained from the reaction, wash it 3 times with deionized water and absolute ethanol respectively, and freeze-dry to obtain a hydrothermal product.

[0103] (4) Thermally activate the hydrothermal product in an air atmosphere at 600 °C for 4 h to obtain an activated powder with upconversion fluorescence, denoted as FYUM.

[0104] (5) Add FYUM to an aqueous solution of iron nitrate with a concentration of 0.1 mmol / L, control the mass ratio of FYUM to the aqueous solution of iron nitrate to be 1:50, stir well, carry out a hydrothermal reaction at 200 °C for 1 h, so that part of the calcium ions and / or rare earth ions on the surface of FYUM are replaced by iron ions, filter, collect the precipitate obtained from the reaction, wash it 3 times with deionized water and absolute ethanol respectively, and freeze-dry to obtain the fluorapatite material FAp: Yb / Eu / Mo / Fe with both upconversion fluorescence and photothermal conversion, abbreviated as FYUM / Fe.

Claims

1. A method for preparing a fluoroapatite material having both upconversion fluorescence and photothermal conversion, characterized in that: The following steps are involved: (1) Ca 2+ Source, Ln1 3+ Source, Ln2 3+ The source was dissolved in deionized water to obtain solution A; in solution A, Ln1 3+ 、Ln2 3+ With Ca 2+ The molar ratio is (5~20): (0.05~2): (78~94.95); Ln1 3+ With Ln2 3+ For different rare earth ions; Ln1 3+ Yb 3+ , Ln2 3+ For Ho 3+ , Er 3+ 、Tm 3+ 、Nd 3+ 、Dy 3+ , Pr 3+ 、Eu 3+ , Tb 3+ 、Sm 3+ 、Ce 3+ At least one of; PO4 3- Source, F - Source and MoO4 2- The source is dissolved in deionized water to obtain solution B; in solution B, the molar ratio of P to Mo is (80-92):(8-20), and the ratio of the sum of the molar amounts of P and Mo to the molar amount of F is 3:1; (2) adding solution B dropwise to solution A at 20-80°C with stirring, controlling the pH value of the resulting mixed solution to be between 9 and 10 during the addition, and continuing to stir for 1-2 hours after the addition is completed to obtain a reaction precursor solution; controlling the ratio of the sum of the molar amounts of Ca, Ln1 and Ln2 to the sum of the molar amounts of P and Mo in the reaction precursor solution to be 5:3; (3) subjecting the reaction precursor solution to a hydrothermal reaction at 120-200 °C, collecting the precipitate obtained by the reaction, washing it, and drying it to obtain a hydrothermal product; (4) subjecting the hydrothermal product to thermal activation treatment in an air atmosphere at 600-1000°C to obtain an activated powder; (5) Disperse the activated powder fully in Fe 3+ In aqueous solution, Fe 3+ Fe in aqueous solution 3+ The concentration of activated powder is 0.1~10mmol / L, controlling the 3+ The mass ratio of the aqueous solution is 1:(10~100), and the hydrothermal reaction is carried out at 120~200℃ for 1~24h. The precipitate obtained by the reaction is collected, washed, and dried to obtain the product.

2. The method for preparing the fluoroapatite material having both upconversion fluorescence and photothermal conversion according to claim 1, characterized in that: Ca in solution A 2+ The concentration of PO4 in solution B is 10~2000 mmol / L. 3- The concentration is 5~500 mmol / L.

3. The method for preparing the fluoroapatite material having both upconversion fluorescence and photothermal conversion according to claim 1 or 2, characterized in that: The time of the hydrothermal reaction in step (3) is controlled to be 4 to 24 h.

4. The method for preparing the fluoroapatite material having both upconversion fluorescence and photothermal conversion according to claim 1 or 2, characterized in that: In step (4), the time of thermal activation treatment is controlled to be 1 to 4 h.

5. The method for preparing the fluoroapatite material having both up-conversion fluorescence and photothermal conversion according to claim 1 or 2, characterized in that: Ca 2+ Source: Ca 2+ Water-soluble salts, Ln1 3+ Source is Ln1 3+ Water-soluble salt, Ln2 3+ Source is Ln2 3+ Water-soluble salt, PO4 3- The source is trisodium phosphate, diammonium hydrogen phosphate or diammonium phosphate, and the F - The source is sodium fluoride or ammonium fluoride, MoO4 2- The source is ammonium molybdate.

6. Fluorapatite material having both upconversion fluorescence and photothermal conversion prepared by the method of claim 1 or 2.

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