Preparation method of semiconductor phase fe s ultra-small nanodots and use thereof

Abstract

The application discloses a preparation method of semiconductor-phase FeS ultra-small nanodots, which comprises the following steps: S1, preparing metal-phase FeS ultra-small nanodots; S2, dispersing the metal-phase FeS ultra-small nanodots in ethylene glycol containing sodium citrate, carrying out high-temperature hydrothermal reaction in an inert atmosphere, purifying the product, and then dispersing the product in ultrapure water to obtain the semiconductor-phase FeS ultra-small nanodots. The method is simple, fast, efficient, low in cost, high in reproducibility, convenient for batch production, and safe in operation, and is a method for rapidly synthesizing semiconductor-phase FeS ultra-small nanodots.

Description

Technical Field

[0001] This invention relates to a method for preparing semiconductor phase FeS ultrasmall nanodots (S-FeS) and their applications, belonging to the field of nanobiomedical technology. Background Technology

[0002] Multimodal imaging therapy reagents play an important role in the integrated diagnosis and treatment of tumors, demonstrating the following advantages: (1) Combining different imaging methods (such as MRI, PAI, CT, etc.) can provide multidimensional and multi-angle tumor information, comprehensively assessing tumor characteristics; (2) Combining multiple imaging technologies can improve the accuracy of tumor diagnosis, enabling precise diagnosis and localization, and more accurately assessing tumor metastasis and spread, avoiding unnecessary treatment methods; (3) During multimodal imaging therapy, tumor changes can be monitored in a timely manner, the treatment effect can be evaluated, and a reference can be provided for subsequent treatment. Nanophase modulation technology is of great significance for the synthesis of high-performance multimodal imaging therapy reagents, showing a significant role in improving the photothermal, photoacoustic, and magnetic properties of nanomaterials. By regulating the crystal structure of nanomaterials, the light absorption characteristics of nanomaterials can be adjusted, thereby improving photothermal and photoacoustic properties and enhancing the effects of photothermal therapy and photoacoustic imaging; Phase modulation technology can also change the magnetic interaction of nanomaterials, thereby improving magnetic properties and enhancing magnetic imaging performance.

[0003] Transition metal chalcogenides (TMCs) have attracted widespread attention in the biomedical field due to their large specific surface area, low cytotoxicity, and strong near-infrared light absorption. FeS nanomaterials, as a unique type of TMC, exhibit great potential in multimodal imaging therapy due to their excellent near-infrared photothermal and photoacoustic properties, as well as magnetic imaging performance. However, the reported near-infrared II photothermal and photoacoustic properties and magnetic imaging performance of FeS nanomaterials are not outstanding enough, which greatly limits their application in multimodal imaging therapy. Therefore, preparing semiconductor-phase FeS ultrasmall nanodots through phase modulation techniques and controlling their phase (crystal phase, size, morphology, etc.) to improve their near-infrared II photothermal and photoacoustic properties and magnetic imaging performance is of great significance for developing multimodal imaging therapy agents based on iron-sulfur compounds and applying them to medical diagnosis and treatment. Summary of the Invention

[0004] Objective: To address the shortcomings of existing metallic FeS ultrasmall nanodots, this invention provides a method for preparing and applying semiconductor-phase FeS ultrasmall nanodots. The semiconductor-phase FeS ultrasmall nanodots prepared by this invention possess excellent NIR-II photothermal, photoacoustic, and magnetic imaging properties, enabling the construction of a high-performance multimodal imaging and therapeutic nanoplatform for tumors, achieving precise tumor treatment.

[0005] This invention is achieved through the following technical solution:

[0006] A method for preparing FeS ultrasmall nanodots in the semiconductor phase includes the following steps:

[0007] S1. Preparation of metallic phase FeS ultrasmall nanodots;

[0008] S2. The metal phase FeS ultrasmall nanodots are dispersed in ethylene glycol containing organic acid salts, and after a high-temperature hydrothermal reaction in an inert atmosphere, the product is purified and dispersed in ultrapure water to obtain the semiconductor phase FeS ultrasmall nanodots.

[0009] As a preferred embodiment, the method for preparing the metallic FeS ultrasmall nanodots is as follows:

[0010] Polyvinylpyrrolidone, ferrous chloride, and L-cysteine ​​were sequentially dissolved in ultrapure water, mixed thoroughly, and then subjected to a hydrothermal reaction at 120–150 °C to obtain metallic FeS ultrasmall nanodots.

[0011] As a preferred embodiment, the temperature of the high-temperature hydrothermal reaction in step S2 is 180–220°C.

[0012] As a preferred embodiment, the organic acid salt is sodium citrate.

[0013] As a preferred embodiment, the purification method described in step S2 is as follows:

[0014] S21. After dispersing the product in acetone, perform high-speed centrifugation and collect the lower precipitate.

[0015] S22. Disperse the lower precipitate collected in step S21 in ultrapure water, perform low-speed centrifugation, and collect the supernatant.

[0016] S23. The supernatant collected in step S22 is centrifuged at high speed to separate the lower precipitate.

[0017] As a preferred embodiment, the high-speed centrifugal separation speed in step S21 is 10,000 to 15,000 rpm.

[0018] As a preferred embodiment, the rotation speed of the low-speed centrifugation in step S22 is 3000 to 7000 rpm.

[0019] As a preferred embodiment, the high-speed centrifugal separation speed in step S23 is 20,000 to 25,000 rpm.

[0020] A semiconductor phase FeS ultrasmall nanodot obtained by the aforementioned preparation method.

[0021] The use of FeS ultrasmall nanodots, a semiconductor phase, as described above, in photothermal therapy materials.

[0022] The present invention uses a hydrothermal synthesis method, which is simple, fast, efficient, low-cost, highly reproducible, easy for mass production, and safe to operate. It is a method for rapidly synthesizing semiconductor phase FeS ultrasmall nanodots.

[0023] The semiconductor phase FeS ultrasmall nanodots described in this invention enable highly efficient photothermal therapy in the NIR-II region, exhibiting the characteristic of deeper tissue penetration and allowing for a higher upper limit of laser radiation, thus greatly improving the effect of photothermal therapy.

[0024] The semiconductor phase FeS ultrasmall nanodots described in this invention utilize the complementary characteristics of photoacoustic imaging (PAI) and magnetic resonance imaging (MRI) to combine the two imaging methods, enabling more comprehensive information acquisition.

[0025] The semiconductor phase FeS ultrasmall nanodots described in this invention simultaneously possess NIR-II region photothermal, photoacoustic, and magnetic imaging properties, and exhibit good biocompatibility. They can realize efficient photothermal therapy guided by multimodal imaging of tumors, and play a positive role in promoting the application of transition metal sulfide nanomaterials in tumor diagnosis and treatment. Attached Figure Description

[0026] Other features, objects, and advantages of the present invention will become more apparent from the following detailed description of non-limiting embodiments with reference to the accompanying drawings:

[0027] Figure 1 This is a TEM image of the FeS ultrasmall nanodots in the semiconductor phase prepared in Example 1 of this invention;

[0028] Figure 2 This is an HRTEM image of the FeS ultrasmall nanodots in the semiconductor phase prepared in Example 1 of this invention;

[0029] Figure 3 The XRD pattern of the semiconductor phase FeS ultrasmall nanodots prepared in Example 1 of this invention;

[0030] Figure 4 This is a high-resolution XPS image of the FeS ultrasmall nanodots in the semiconductor phase prepared in Example 1 of this invention;

[0031] Figure 5 This is a high-resolution XPS image of Fe 2p in the FeS ultrasmall nanodots prepared in Example 1 of this invention;

[0032] Figure 6 This is a high-resolution XPS image of S2p in the FeS ultrasmall nanodots prepared in Example 1 of this invention;

[0033] Figure 7 This is a comparison of the Raman spectra of metallic FeS ultrasmall nanodots and semiconductor FeS ultrasmall nanodots prepared in Example 1 of this invention;

[0034] Figure 8 Comparison of UV-vis-NIR absorption spectra of semiconductor phase FeS ultra-small nanodot aqueous suspension and metal phase FeS ultra-small nanodot aqueous suspension of the same concentration prepared in Example 1 of this invention.

[0035] Figure 9 The images show the UV-vis-NIR absorption spectra (a) and linear fitting lines (b) between absorbance and concentration at 1064 nm for FeS ultra-small nanodot aqueous suspensions of different concentrations prepared in Example 1 of this invention, as well as the UV-vis-NIR absorption spectra (c) and linear fitting lines (d) between absorbance and concentration at 1064 nm for FeS ultra-small nanodot aqueous suspensions of different concentrations.

[0036] Figure 10 The graphs shown are: (a) the heating and cooling curves of the semiconductor phase FeS ultra-small nanoparticle aqueous suspension prepared in Example 1 of this invention under 1064nm laser irradiation for 20 min and (b) the relationship between time t and lnθ during the 10 min cooling process; and (c) the heating and cooling curves of the metallic phase FeS ultra-small nanoparticle aqueous suspension under 1064nm laser irradiation for 20 min and (d) the relationship between time t and lnθ during the 10 min cooling process.

[0037] Figure 11 The heating / cooling curves (a) of the semiconductor phase FeS ultra-small nanoparticle aqueous suspension prepared in Example 1 of this invention under five 1064nm laser on / off cycles and (b) of the metallic phase FeS ultra-small nanoparticle aqueous suspension under five 1064nm laser on / off cycles are shown.

[0038] Figure 12 The photoacoustic signal intensity diagrams of semiconductor phase FeS ultrasmall nanodots and metallic phase FeS ultrasmall nanodots prepared in Example 1 of this invention under 1064nm laser light in aqueous suspensions of different concentrations.

[0039] Figure 13 The relationship between the photoacoustic signal intensity and concentration of semiconductor phase FeS ultrasmall nanodots and metallic phase FeS ultrasmall nanodots prepared in Example 1 of this invention under 1064nm laser light (the upper inset shows the photoacoustic imaging cross-sections corresponding to each concentration of M-FeS, and the lower inset shows the photoacoustic imaging cross-sections corresponding to each concentration of S-FeS).

[0040] Figure 14 Linear fitting diagrams of T2 and T1 weighted relaxation rates of the semiconductor phase FeS ultrasmall nanodots prepared in Example 1 of this invention (the upper inset is the T2 weighted magnetic resonance imaging corresponding to each concentration of S-FeS, and the lower inset is the T1 weighted magnetic resonance imaging corresponding to each concentration of S-FeS).

[0041] Figure 15 The image shows the linear fitting plots of the T2 and T1 weighted relaxation rates of the metallic FeS ultrasmall nanodots prepared in Example 1 of this invention (the top inset is the T2 weighted magnetic resonance imaging corresponding to each concentration of M-FeS, and the bottom inset is the T1 weighted magnetic resonance imaging corresponding to each concentration of M-FeS).

[0042] Figure 16 The cell viability of 3T3 normal cells after incubation with the semiconductor phase FeS ultrasmall nanodots prepared in Example 1 of this invention;

[0043] Figure 17 Photoacoustic imaging of the semiconductor phase FeS ultrasmall nanodots and the metallic phase FeS ultrasmall nanodots prepared in Example 1 of this invention injected into mice 24 hours later.

[0044] Figure 18 Photoacoustic imaging intensity diagrams of semiconductor phase FeS ultrasmall nanodots and metallic phase FeS ultrasmall nanodots prepared in Example 1 of this invention, injected into mice within 24 hours.

[0045] Figure 19 The images show T2-weighted magnetic resonance images of the semiconductor phase FeS ultrasmall nanodots and the metallic phase FeS ultrasmall nanodots prepared in Example 1 of this invention, injected into mice within 24 hours.

[0046] Figure 20 The images show the T2-weighted magnetic resonance imaging intensity of the semiconductor phase FeS ultrasmall nanodots and the metallic phase FeS ultrasmall nanodots prepared in Example 1 of this invention, injected into mice within 24 hours.

[0047] Figure 21 The photothermal heating curves of the semiconductor phase FeS ultrasmall nanodots and the metallic phase FeS ultrasmall nanodots prepared in Example 1 of this invention after being injected into 4T1 tumor-bearing mice under 1064nm laser irradiation are shown.

[0048] Figure 22 The graph shows the tumor volume change curves of the semiconductor phase FeS ultrasmall nanodots and the metallic phase FeS ultrasmall nanodots prepared in Example 1 of this invention after 18 days of injection into 4T1 tumor-bearing mice. Detailed Implementation

[0049] The present invention will now be described in detail with reference to specific embodiments. These embodiments will help those skilled in the art to further understand the present invention, but do not limit the invention in any way. It should be noted that those skilled in the art can make various modifications and improvements without departing from the concept of the present invention. These all fall within the scope of protection of the present invention.

[0050] All raw materials used in this invention are commercially available. Among them, polyvinylpyrrolidone (PVP29000), FeCl2·4H2O, L-cysteine, ethylene glycol, and sodium citrate dihydrate (C6H5Na3O7) were all purchased from Sigma-Aldrich.

[0051] Example 1

[0052] This embodiment provides a method for preparing FeS ultrasmall nanodots in the semiconductor phase, specifically including the following steps:

[0053] Weigh 400 mg PVP29000, 30 mg FeCl2·4H2O and 60 mg L-cysteine, dissolve them in 50 mL of ultrapure water, and stir for 10 min until the mixture is homogeneous to obtain the reaction solution.

[0054] The reaction solution was loaded into a reaction vessel and placed in an oven. The reaction temperature was set to 160℃ and the reaction time to 4h for hydrothermal synthesis. After cooling, the product was centrifuged at 5000rpm, and the supernatant was collected. The product was then centrifuged again at 21000rpm, and the precipitate was redispersed in 50mL of ethylene glycol.

[0055] 5 mg of sodium tricitrate was dissolved in the above solution and transferred to the inner liner of the reactor. After purging with argon gas for 30 min, the reactor was placed in the outer shell and placed in an oven. Hydrothermal synthesis was performed at a reaction temperature of 200℃ for 12 h. After cooling, the product was purified by centrifugation. The purification steps were as follows: ① The initial product was mixed with acetone at a ratio of 1:2 and centrifuged at 12000 rpm to collect the lower precipitate; ② The precipitate from ① was dispersed in ultrapure water and centrifuged at 5000 rpm to collect the supernatant; ③ The supernatant from ② was centrifuged at 21000 rpm to collect the lower precipitate and redispersed in ultrapure water to finally obtain the semiconductor phase FeS ultrasmall nanodots.

[0056] The FeS ultrasmall nanodots of the semiconductor phase prepared in this embodiment were characterized by TEM images ( Figure 1 The obtained FeS semiconductor phase ultrasmall nanoparticles were observed to be uniformly dispersed, with an average particle size of approximately 2–4 nm. Their lattice data were analyzed using HRTEM. Figure 2 The lattice spacing of the FeS ultrasmall nanodots in the semiconductor phase is 0.209 nm, corresponding to the (114) crystal plane of FeS, which is consistent with XRD characterization. Figure 3 The results are consistent. The atomic valence states of the FeS ultrasmall nanodots in the semiconductor phase were determined by X-ray photoelectron spectroscopy (XPS), such as... Figures 4-6 As shown, the binding energy peaks of Fe and S elements are clearly visible in the full spectrum. Fe 2p has six XPS spectral peaks, with the two binding energy peaks at 707.5 eV and 721.0 eV belonging to Fe, respectively. 2+ Fe 2p 3 / 2 and Fe 2P 1 / 2 The two binding energy peaks at 709.5 eV and 721.0 eV are attributed to Fe, respectively. 3+ Fe 2p 3 / 2 and Fe 2p 1 / 2 The two binding energy peaks at 712.1 eV and 733.6 eV are attributed to Fe, respectively. 2+ and Fe 3+ The satellite peaks; the XPS spectral peaks of S2p are located at 160.8 eV and 161.9 eV, which are attributed to -2 valence S2p, respectively. 3 / 2 and S2p 1 / 2 Raman spectral characterization of metallic FeS ultrasmall nanodots and semiconductor FeS ultrasmall nanodots is as follows: Figure 7 As shown, the Raman characteristic peak of the semiconductor phase FeS ultrasmall nanodots shows a significant red shift compared to the metallic phase FeS ultrasmall nanodots, proving that the material has transformed from a metallic phase to a semiconductor phase. TEM, HRTEM, XPS, and Raman characterization confirm the successful synthesis of the semiconductor phase FeS ultrasmall nanodots. A comparison of the UV-vis-NIR spectra of aqueous suspensions of semiconductor phase FeS ultrasmall nanodots and metallic phase FeS ultrasmall nanodots at the same concentration is shown below. Figure 8 As shown, the former has a significantly higher absorbance than the latter, exhibiting stronger light absorption capability. The UV-vis-NIR spectra and mass extinction coefficients of aqueous suspensions of FeS ultrasmall nanodots with different concentrations of semiconductor phase and metallic phase are shown in the figure. Figure 9 As shown, the aqueous suspension of FeS ultrasmall nanodots in the semiconductor phase exhibits significant optical absorption in the NIR-II window. Figure 9 a) Using the Lambert-Beer law to fit a linear relationship between different material concentrations and their absorbance at 1064 nm, the calculated mass extinction coefficient ε of the FeS ultrasmall nanodots at 1064 nm is 35.17 L g. -1 cm -1 ( Figure 9 b). Absorbance values ​​of FeS ultrasmall nanodot aqueous suspension at the same concentration ( Figure 9 a) The absorbance value is significantly higher than that of the FeS ultra-small nanoparticle aqueous suspension in the metallic phase. Figure 9c), its mass extinction coefficient (35.17 L g) -1 cm -1 ()( Figure 9 b) The mass extinction coefficient is significantly higher than that of metallic FeS ultrasmall nanodots (22.43 L g). -1 cm -1 ()( Figure 9 d).

[0057] The photothermal properties of the semiconductor phase FeS ultrasmall nanodots and the metallic phase FeS ultrasmall nanodots prepared in Example 1 were characterized. Figure 10 It can be known that 30 μg mL -1 Both materials heated to above 50°C after 10 min of 1064 nm laser irradiation, but the temperature rise of the semiconducting FeS ultrasmall nanodot aqueous suspension was more significant, making it an excellent photothermal agent for killing tumor cells. The photothermal conversion efficiency of the semiconducting FeS ultrasmall nanodots and the metallic FeS ultrasmall nanodots was calculated using methods reported in the literature. The photothermal conversion efficiency of the semiconducting FeS ultrasmall nanodots was 40% (…). Figure 10 a, b), higher than 35% of metallic FeS ultrasmall nanodots ( Figure 10 (c, d) Semiconductor-phase FeS ultrasmall nanodots and metallic-phase FeS ultrasmall nanodots of the same concentration were selected for photothermal stability testing under a 1064 nm laser. After five cycles of laser irradiation for 10 min followed by 10 min of cooling, the cooling cycle curves of the aqueous suspensions of semiconductor-phase FeS ultrasmall nanodots and metallic-phase FeS ultrasmall nanodots were obtained as shown below. Figure 11 a and Figure 11 As shown in b, the temperature difference did not change significantly during each heating / cooling cycle, indicating that the semiconductor phase FeS ultrasmall nanodots can be used as a photothermal therapy agent with high photothermal conversion efficiency and stability for the photothermal treatment of related tumors.

[0058] The photoacoustic properties of the semiconductor phase FeS ultrasmall nanodots prepared in Example 1 were characterized and compared with those of the metallic phase FeS ultrasmall nanodots prepared in Comparative Example 1. Figure 12 and Figure 13 As shown, the photoacoustic signals of both under 1064nm laser show a good linear correlation with their respective concentrations. Moreover, at the same concentration, the photoacoustic signal intensity of the semiconductor phase FeS ultrasmall nanodots is much higher than that of the metallic phase FeS ultrasmall nanodots, indicating that the semiconductor phase FeS ultrasmall nanodots have superior photoacoustic performance and are expected to be used for photoacoustic imaging in the NIR-II window, making them a very promising photoacoustic contrast agent.

[0059] The FeS ultrasmall nanodots of the semiconductor phase prepared in Example 1 were characterized by magnetic resonance imaging, such as... Figure 14As shown, the calculated relaxation rate r² of the FeS ultrasmall nanodots in the semiconductor phase is 114.53 mM. -1 s -1 This is significantly higher than the 29.43 mM of the FeS ultrasmall nanodots prepared in Comparative Example 1. -1 s -1 ( Figure 15 This indicates that the semiconductor phase FeS ultrasmall nanodots we synthesized have superior T2-weighted magnetic resonance imaging performance.

[0060] Besides the excellent photothermal, photoacoustic, and magnetic resonance imaging properties of the semiconductor phase FeS ultrasmall nanodots, they also exhibit good biocompatibility and in vivo imaging therapeutic effects in biological applications. The semiconductor phase FeS ultrasmall nanodots prepared in Example 1 were subjected to cell-level experiments, such as... Figure 16 As shown, MTT assays were performed to evaluate biocompatibility by co-incubating FeS ultrasmall nanodots of different mass concentrations with 3T3 cells in the range of 0–130 μg / mL. -1 Within the concentration range, when the concentration of ultrasmall FeS nanodots is as high as 80 μg / mL -1 Even after that, the cell viability remained above 80%, indicating that it has good biocompatibility in biological applications.

[0061] The semiconductor-phase FeS ultrasmall nanodots prepared in Example 1 and the metallic-phase FeS ultrasmall nanodots prepared in Comparative Example 1 were compared using photoacoustic imaging in 4T1 tumor-bearing mice. Photoacoustic imaging and photoacoustic intensity at the tumor site within 24 hours after intravenous injection of the same concentration of the two materials into the 4T1 tumor-bearing mice are shown below. Figure 17 and Figure 18 As shown, the material gradually accumulates at the tumor site within 0 to 10 hours, reaching a peak at 10 hours. At this time, the photoacoustic signal intensity of the semiconductor phase FeS ultrasmall nanodots is much higher than that of the metallic phase FeS ultrasmall nanodots, indicating that the semiconductor phase FeS ultrasmall nanodots prepared in Example 1 have better in vivo photoacoustic imaging performance and are a safe and promising biophotoacoustic imaging contrast agent.

[0062] The semiconductor-phase FeS ultrasmall nanodots prepared in Example 1 and the metallic-phase FeS ultrasmall nanodots prepared in Comparative Example 1 were compared using in vivo magnetic resonance imaging (MRI) in 4T1 tumor-bearing mice. The MRI and MRI signal intensity of the tumor site within 24 hours after intravenous injection of the same concentration of the two materials into the 4T1 tumor-bearing mice are shown below. Figure 19 and Figure 20As shown, the material gradually accumulates at the tumor site within 0 to 10 hours, reaching a peak at 10 hours. At this time, the magnetic resonance signal intensity of the semiconductor phase FeS ultrasmall nanodots is much higher than that of the metallic phase FeS ultrasmall nanodots, indicating that the semiconductor phase FeS ultrasmall nanodots prepared in Example 1 have better in vivo magnetic resonance imaging performance and are a safe and promising contrast agent for biomagnetic resonance imaging.

[0063] Near-infrared II photothermal therapy was compared between the semiconductor-phase FeS ultrasmall nanodots prepared in Example 1 and the metallic-phase FeS ultrasmall nanodots prepared in Comparative Example 1 on 4T1 tumor-bearing mice. After intravenous injection of the same concentration of each material into the 4T1 tumor-bearing mice for 10 hours, the tumor sites were treated with 1064nm laser photothermal therapy. The photothermal heating curves are shown below. Figure 21 As shown, the tumor site temperature of the semiconductor phase FeS ultrasmall nanodot group was significantly higher than that of the metallic phase FeS ultrasmall nanodot group. The changes in tumor volume in mice within 18 days after 1064nm laser photothermal treatment are shown in the figure. Figure 22 As shown, near-infrared II photothermal therapy using semiconductor-phase FeS ultrasmall nanodots resulted in a significant reduction in tumor volume, with therapeutic effects superior to the group without photothermal therapy and the group using metallic-phase FeS ultrasmall nanodots. These biological experimental results demonstrate that our synthesized semiconductor-phase FeS ultrasmall nanodots possess excellent biocompatibility and performance in photothermal therapy, photoacoustic imaging, and magnetic resonance imaging, making them suitable as a multimodal imaging therapy reagent for tumors.

[0064] Comparative Example 1

[0065] This comparative example uses metallic FeS ultrasmall nanodots (M-FeS) as the precursor material for Example 1. The synthesis steps are as follows:

[0066] Weigh 400 mg PVP29000, 30 mg FeCl2·4H2O and 60 mg L-cysteine ​​and dissolve them in 50 mL of ultrapure water. Stir for 10 min until the mixture is homogeneous to obtain the reaction solution.

[0067] The reaction solution was placed in a reaction vessel and then in an oven. Hydrothermal synthesis was performed at a reaction temperature of 160°C for 4 hours. After cooling, the product was centrifuged at 5000 rpm, and the supernatant was collected and centrifuged again at 21000 rpm. The precipitate was redispersed in ultrapure water and centrifuged again at 21000 rpm. The resulting precipitate was then dispersed in ultrapure water to finally obtain the metallic phase FeS ultrasmall nanodots. The UV-vis-NIR optical absorbance, photothermal conversion efficiency, in vitro photoacoustic signal intensity, in vitro magnetic resonance imaging signal intensity, in vivo photoacoustic imaging signal intensity, and in vivo magnetic resonance imaging signal intensity of the metallic phase FeS ultrasmall nanodots at the same concentration were all inferior to those of the semiconductor phase FeS ultrasmall nanodots prepared in Example 1. Figure 8-9 , Figure 12-15 , Figure 17-20 ).

[0068] Comparative Example 2

[0069] The preparation method of this comparative example is basically the same as that of Example 1, except that the solvent ethylene glycol is replaced with N,N-dimethylformamide. After solvothermal reaction regulation with this solvent, the absorption of FeS ultrasmall nanodots in the near-infrared region is not significantly improved.

[0070] Comparative Example 3

[0071] The preparation method of this comparative example is basically the same as that of Example 1, except that L-cysteine ​​is replaced with thiourea for the reaction. The FeS nanodots prepared are larger in size, and the heating rate under 1064nm laser irradiation is significantly lower than that of the semiconductor phase FeS ultrasmall nanodots prepared in Example 1.

[0072] The specific embodiments of the present invention have been described above. It should be understood that the present invention is not limited to the specific embodiments described above, and those skilled in the art can make various modifications or variations within the scope of the claims, which do not affect the essence of the present invention.

Claims

1. A method for preparing FeS ultrasmall nanodots in the semiconductor phase, characterized in that, Includes the following steps: S1. Preparation of metallic phase FeS ultrasmall nanodots; S2. The metallic FeS ultrasmall nanodots are dispersed in ethylene glycol containing organic acid salts, and after a high-temperature hydrothermal reaction in an inert atmosphere, the product is purified and dispersed in ultrapure water to obtain the semiconductor FeS ultrasmall nanodots. The temperature of the high-temperature hydrothermal reaction in step S2 is 180~220℃; The organic acid salt is sodium citrate.

2. The method for preparing FeS ultrasmall nanodots in semiconductor phase as described in claim 1, characterized in that, The method for preparing the FeS ultrasmall nanodots of the metallic phase is as follows: Polyvinylpyrrolidone, ferrous chloride, and L-cysteine ​​were sequentially dissolved in ultrapure water, mixed thoroughly, and then subjected to a hydrothermal reaction at 120-150°C to obtain metallic FeS ultrasmall nanodots.

3. The method for preparing FeS ultrasmall nanodots in semiconductor phase as described in claim 1, characterized in that, The purification method described in step S2 is as follows: S21. After dispersing the product in acetone, perform high-speed centrifugation and collect the lower precipitate. S22. Disperse the lower precipitate collected in step S21 in ultrapure water, perform low-speed centrifugation, and collect the supernatant. S23. The supernatant collected in step S22 is centrifuged at high speed to separate the lower precipitate.

4. The method for preparing FeS ultrasmall nanodots in semiconductor phase as described in claim 3, characterized in that, The high-speed centrifugation speed described in step S21 is 10,000 to 15,000 rpm.

5. The method for preparing FeS ultrasmall nanodots in semiconductor phase as described in claim 3, characterized in that, The rotation speed of the low-speed centrifugation separation described in step S22 is 3000~7000 rpm.

6. The method for preparing FeS ultrasmall nanodots in semiconductor phase as described in claim 3, characterized in that, The high-speed centrifugation speed described in step S23 is 20,000 to 25,000 rpm.

7. A semiconductor phase FeS ultrasmall nanodot obtained by the preparation method described in claim 1.

8. Use of the semiconductor phase FeS ultrasmall nanodots as described in claim 7 in photothermal therapy materials.

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