An MXene / In / PDA Photothermal Composite Material, Its Preparation Method and Application

Abstract

The present invention discloses a MXene / In / PDA photothermal composite material composed of MXene, In nanoparticles, and PDA. The In nanoparticles and PDA are in situ loaded on the MXene, exhibiting a rough, flaky morphology. The MXene serves as a photosensitizer for PDT and a carrier for PTT and PDT, enabling combined PTT and PDT therapy. In provides a photothermal effect to kill cancer cells, and PDA removes the toxicity of pure MXene, providing biocompatibility. The preparation method comprises the following steps: 1. Preparation of MXene; 2. Simultaneous in situ preparation of In and PDA. For tumor treatment applications, the composite material exhibits photothermal properties with a maximum photothermal conversion temperature of 38-62°C; photothermal cycle stability; and therapeutic selectivity, namely, near-infrared response, generating toxic reactive oxygen species (ROS) under laser irradiation. The composite material has the advantages of high photothermal conversion performance and photothermal cycle stability, as well as therapeutic selectivity, simple process, low cost, short reaction cycle, low energy consumption, and low pollution.

Description

Technical Field

[0001] The present invention relates to the field of tumor treatment, and in particular to a MXene / In / PDA photothermal composite material and a preparation method and application thereof. Background Art

[0002] Current cancer treatments, in addition to traditional chemotherapy and radiotherapy, also involve killing cancer cells through the generation of heat and reactive oxygen species. Directly using heat or reactive oxygen species to treat cancer suffers from the same technical issues as traditional chemotherapy and radiotherapy: while killing cancer cells, they can also cause severe damage to normal cells, resulting in serious side effects.

[0003] Heat generation can be achieved by light-stimulating photothermal materials, a technique known as photothermal therapy (PTT). It should be noted that PTT's technical solution features near-infrared response, enabling selective treatment. Metal nanoparticles are a common photothermal material.

[0004] For example, in the existing document 1 (Chen Y, Wu H, Zhou H, et al. PEGylated Indium Nanoparticles: AMetallic Contrast Agent for Multiwavelength Photoacoustic Imaging and SecondNear-Infrared Photothermal Therapy [J]. ACS Applied Materials & Interfaces, 2021, 13 (39): 46343-46352.), methoxy-PEG-thiol (mPEG-SH) was used as a capping agent and NaBH4 was used as a reducing agent to rapidly synthesize PEGylated In nanoparticles in an ultrasonic bath. This technical solution utilizes In nanoparticles to obtain photothermal properties, generates heat through near-infrared laser irradiation, achieves effective ablation of 4T1 tumors, and has good photothermal cycle characteristics. However, this specific technical solution still has the following technical problems: 1. The single PTT treatment effect is single and has limitations; 2. The cost of functionalized PEG is relatively high.

[0005] For example, in the existing document 2 (Hussein EA, Zagho MM, Rizeq BR, et al. Plasmonic MXene-based nanocomposites exhibiting photothermal therapeutic effects with lower acute toxicity than pure MXene [J]. International journal of nanomedicine, 2019: 4529-4539.), Au nanoparticles and magnetic Fe3O4 are simultaneously loaded onto MXene, and Au nanoparticles are used to obtain photothermal properties, and magnetic Fe3O4 is used to achieve targeted therapy.

[0006] Combined with existing literature 3 ( AM, Szuplewska A, Wojciechowski T, et al. In vitro studies on cytotoxicity of delaminated Ti3C2 MXene[J]. Journal of hazardous materials, 2017, 339: 1-8.) It can be seen that pure MXene causes 100% mortality at a concentration of 21 μg / mL.

[0007] Experimental results from existing literature 2 show that the ROS removal properties of MXene can be achieved by combining Au nanoparticles and magnetic Fe₃O₄. However, this also eliminates the MXene's ability to kill cancer cells. The technical effect of magnetic Fe₃O₄ in this technical solution, due to its targeted therapeutic properties, is unrelated to the technical problem to be solved by the present invention.

[0008] Therefore, the inventors have found that the biocompatibility can be improved by selecting an appropriate coating material such as PDA. Summary of the Invention

[0009] The present invention aims to provide a MXene / In / PDA photothermal composite material, which is synthesized by ultrasonic reduction method and used as a photothermal therapeutic agent.

[0010] The present invention aims to solve the technical problems existing in the prior art by adopting the following methods:

[0011] 1. In nanoparticles are difficult to maintain stability when they exist alone, so they need to be stabilized by a carrier. At the same time, the subsequent compounding with MXene can achieve the technical effect of reducing the toxicity of pure MXene.

[0012] 2. In addition to the properties of ROS, MXene itself also has the characteristics of large specific surface area, good hydrophilicity, and active sites, and can be used as a carrier;

[0013] 3. Since the combination of metal and MXene will produce a new technical problem - charge neutralization leads to the deposition defect of composite nanomaterials, which limits its application in the field of cell therapy, polydopamine is used as a reducing agent and sodium citrate as a stabilizer to improve the dispersibility of composite nanomaterials in water;

[0014] 4. At the same time, polydopamine not only acts as a reducing agent but also as a surface modifier in the technical solution. While achieving the corresponding technical effects, it also achieves the effects of simplifying the preparation process and reducing process costs.

[0015] 5. The combination of In nanoparticles and MXene can reduce the toxicity of MXene nanosheets and enhance the photothermal effect of the overall material.

[0016] The technical solution for achieving the purpose of the present invention is:

[0017] A MXene / In / PDA photothermal composite material, characterized by being composed of MXene, In nanoparticles, and PDA, wherein the In nanoparticles and PDA are in situ loaded on the MXene, and the resulting MXene / In / PDA exhibits a rough flaky morphology;

[0018] The MXene plays two roles in the technical solution: one is as a photosensitizer when realizing the photodynamic therapy PDT function, and the other is as a carrier when realizing the photothermal therapy PTT and PDT functions, that is, realizing the combined treatment of PTT and PDT;

[0019] The role of the In nanoparticles in the technical solution is to provide a photothermal effect, that is, to generate heat under laser irradiation to kill cancer cells;

[0020] The role of PDA in the technical solution is to remove the toxicity of pure MXene and provide biocompatibility.

[0021] A method for preparing a MXene / In / PDA photothermal composite material comprises the following steps:

[0022] Step 1, preparation of MXene, LiF is completely dissolved in HCl solution to obtain solution A, then Ti3AlC2 is slowly added to solution A, and an etching reaction is carried out under stirring conditions to etch the Al layer in Ti3AlC2. Finally, the obtained product is centrifuged and washed with deionized water until the supernatant is neutral and freeze-dried to obtain Ti3C2T x , namely MXene;

[0023] In step 1, the molar ratio of LiF to Ti3AlC2 is 9.5:1; the reaction time is 24 hours;

[0024] Step 2: Synchronous in situ preparation of In and PDA. After ultrasonically dispersing the MXene obtained in step 1 in ethanol, sodium citrate and indium chloride solutions were added and ultrasonication was continued to obtain solution B. At the same time, dopamine was added to tris(hydroxymethyl)aminomethane hydrochloride) solution to obtain solution C. Then, solution B and solution C were mixed and ultrasonically reacted under certain conditions. Finally, the obtained product was alternately washed with water and ethanol and freeze-dried to obtain a MXene / In / PDA photothermal composite material, referred to as MXene / In / PDA-300.

[0025] In step 2, the molar ratio of MXene, sodium citrate, and indium chloride is 12:23:27;

[0026] In step 2, the pH of the tris(hydroxymethyl)aminomethane hydrochloride solution is 8.5;

[0027] In step 2, the ultrasonic reaction time is 6 hours.

[0028] A MXene / In / PDA photothermal composite material for tumor treatment has photothermal properties and can be used at a power density of 0.25-1 W / cm 2 The maximum photothermal conversion temperature is 38-62°C when the temperature is within the range of 400-620°C; it has photothermal cycle stability. In 5 cycles of photothermal testing, the temperature difference between the highest temperature and the lowest temperature is less than 5°C; it has therapeutic selectivity, that is, it has the characteristics of near-infrared response and produces toxic reactive oxygen species (ROS) under laser irradiation.

[0029] The technical effects of the present invention have been tested and the specific contents are as follows:

[0030] XRD detection shows that there are characteristic peaks of MXene, and MXene is successfully synthesized.

[0031] TEM examination showed that MXene was used as a carrier, In / PDA nanoparticles were loaded on MXene flakes, and MXene / In / PDA presented a rough flake morphology.

[0032] EDS detection shows that the surface of MXene / In / PDA contains four elements, Ti, In, N, and C, and is evenly distributed. Ti and C are the components of MXene. The detected In and N elements indicate that In and PDA are successfully loaded on the surface of MXene.

[0033] The photothermal test shows that: at a power density of 0.25-1W / cm 2 When the temperature is within the range of , the highest photothermal conversion temperature is 38-62℃;

[0034] Reactive oxygen tests have shown that pure MXene is toxic and uncontrollable, and can produce reactive oxygen with or without laser irradiation; MXene / In / PDA-300 is non-toxic and can achieve selective treatment, achieving local precision treatment by turning the laser on / off.

[0035] Therefore, the MXene / In / PDA composite material of the present invention has the following advantages over the prior art:

[0036] 1. As a photothermal therapy application, MXene / In / PDA composite material has good photothermal conversion performance. At 808nm laser wavelength and power density of 0.25-1W / cm 2 When the temperature is within the range of , the highest photothermal conversion temperature is 38-62℃;

[0037] 2. The MXene / In / PDA composite material has photothermal cycle stability. In the five-cycle photothermal test, the temperature difference between the highest temperature and the lowest temperature is less than 5°C.

[0038] 3. It has therapeutic selectivity and produces toxic reactive oxygen species (ROS) under laser irradiation;

[0039] 4. The synthesis process of the present invention is simple, low in cost, short in reaction cycle, low in energy consumption and low in pollution.

[0040] Therefore, compared with the existing technology, the present invention has better photothermal conversion performance, stability and low toxicity, and has broad application prospects in the field of cancer treatment. BRIEF DESCRIPTION OF THE DRAWINGS

[0041] Figure 1 X-ray diffraction patterns of MXene / In / PDA-300, MXene / In / PDA-100, and MXene / In / PDA-200 in Examples 1, 2, and 3;

[0042] Figure 2 Transmission electron microscopy and EDS spectra of MXene / In / PDA-300 in Example 1;

[0043] Figure 3 This is the photothermal test diagram of MXene / In / PDA-300 in Example 1 under 808nm laser irradiation at different power densities;

[0044] Figure 4This is the photothermal test diagram of MXene / In / PDA-100 in Example 2 under 808nm laser irradiation at different power densities;

[0045] Figure 5 This is the photothermal test diagram of MXene / In / PDA-200 in Example 3 under 808nm laser irradiation at different power densities;

[0046] Figure 6 The MXene / In / PDA in Example 1 was subjected to a laser wavelength of 808 nm and 1.00 W / cm 2 Performance diagram of 5 cycles of light and heat test under different conditions;

[0047] Figure 7 TEM image of MXene / In / PDA-100 in Example 2;

[0048] Figure 8 This is a transmission electron microscopy image of MXene / In / PDA-200 in Example 3;

[0049] Figure 9 This is the ROS cell imaging image of pure MXene without laser irradiation in Example 1;

[0050] Figure 10 This is the ROS cell imaging image of pure MXene irradiated with laser in Example 1;

[0051] Figure 11 This is the ROS cell imaging image of MXene / In / PDA-300 in Example 1 without laser irradiation;

[0052] Figure 12 This is the ROS cell imaging image of MXene / In / PDA-300 under laser irradiation in Example 1. DETAILED DESCRIPTION

[0053] The present invention is further described in detail through embodiments and in conjunction with the accompanying drawings, but the present invention is not limited thereto.

[0054] Example 1

[0055] A method for preparing a MXene / In / PDA photothermal composite material comprises the following steps:

[0056] Step 1, preparation of MXene, 0.5g LiF is completely dissolved in HCl solution to obtain solution A, then Ti3AlC2 is slowly added to solution A, and an etching reaction is carried out under stirring for a reaction time of 24h to etch the Al layer in Ti3AlC2. Finally, the obtained product is centrifuged and washed with deionized water until the supernatant is neutral and freeze-dried to obtain Ti3C2T x , namely MXene;

[0057] Step 2, simultaneous in situ preparation of In and PDA. After ultrasonically dispersing 10 mg of the MXene obtained in step 1 in ethanol, 30 mg of sodium citrate and 300 μL of 100 mg / mL indium chloride solution were added and ultrasonication was continued to obtain solution B. At the same time, dopamine was added to tris(hydroxymethylaminomethane) hydrochloride solution with a pH of 8.5 to obtain solution C. Then, solution B and solution C were mixed and ultrasonically reacted under the condition of an ultrasonic time of 6 h. Finally, the obtained product was alternately washed with water and ethanol and freeze-dried to obtain a MXene / In / PDA photothermal composite material, referred to as MXene / In / PDA-300.

[0058] In order to prove the composition of MXene / In / PDA-300, that is, to prove the successful synthesis, XRD test was carried out. The test results are as follows Figure 1 As shown, MXene / In / PDA-300 has the characteristic peaks of MXene, but the characteristic peaks of In and PDA are not detected;

[0059] In order to further confirm the composition of MXene / In / PDA-300, EDS test was performed. The test results are as follows Figure 2 As shown in the figure, the surface of MXene / In / PDA-300 contains four elements, Ti, In, N, and C, and they are evenly distributed.

[0060] Combining XRD and EDS tests, it can be seen that the detection of In element by EDS indicates that In element is successfully loaded on the surface of MXene, while the failure of XRD to detect In element is due to its low content;

[0061] EDS detected Ti and C elements, which are components of MXene. Therefore, it can be proved that PDA is successfully loaded on the surface of MXene. XRD did not detect MXene because MXene has an amorphous structure. In summary, XRD and EDS tests can prove that MXene / In / PDA-300 was successfully synthesized.

[0062] In order to prove the microstructure of MXene / In / PDA-300, TEM test was carried out. The test results are shown in the figure below. Figure 2As shown, MXene / In / PDA-300 has a flake structure with a rough surface.

[0063] In order to prove that MXene / In / PDA-300 has photothermal properties, photothermal performance tests were carried out.

[0064] The specific test method of the photothermal performance test is as follows: 0.5 mL of MXene / In / PDA-300 is irradiated with a laser at a wavelength of 808 nm and an irradiation time of 10 min under different power density conditions. At the same time, the temperature value of MXene / In / PDA-300 is recorded at a frequency of 2 min / time using an infrared thermal imager, wherein the power density is 0.25 W / cm 2 , 0.51W / cm 2 , 1.00W / cm 2 .

[0065] The photothermal performance test results of MXene / In / PDA-300 are as follows: Figure 3 As shown,

[0066] At a power density of 0.25 W / cm 2 When , the highest photothermal conversion temperature is 38.1℃;

[0067] At a power density of 0.51 W / cm 2 When , the highest photothermal conversion temperature is 54.6℃;

[0068] At a power density of 1.00 W / cm 2 The highest photothermal conversion temperature is 61.5℃.

[0069] In order to prove the photothermal cycling performance of MXene / In / PDA-300, a photothermal cycling performance test was conducted. The specific test method was: repeat the photothermal performance test 5 times. The photothermal cycling performance test results are as follows: Figure 6 As shown in Table 1, in the 5-cycle photothermal test, the temperature difference between the highest temperature and the temperature difference between the lowest temperature were less than 5°C. The test results show that MXene / In / PDA-300 has stable photothermal cycling performance.

[0070] Table 1 Photothermal cycling performance test of MXene / In / PDA-300

[0071]

[0072]

[0073] To demonstrate the ROS-derived cancer cell-killing properties of MXene / In / PDA-300, reactive oxygen species (ROS) levels were tested. Furthermore, to demonstrate the near-infrared-responsive selective therapeutic properties of MXene / In / PDA-300, i.e., its selectivity in addition to its ROS-derived cancer cell-killing properties, reactive oxygen species (ROS) levels were tested in the absence and presence of laser irradiation. Furthermore, for comparison, pure MXene was also tested for ROS levels, and the test results are summarized in Table 2.

[0074] The specific test method for the reactive oxygen species level test is as follows: first, a HeLa cell suspension was inoculated into a 6-well plate and placed in an incubator for incubation overnight; then, MXene / In / PDA-300 was added at a concentration of 150 μg / mL and cultured for 24 hours; after the end of the culture, the cells were washed twice with PBS, replaced with serum-free culture medium and a DCFH-DA probe was added, incubated at 37°C for 30 minutes, and images were captured by a multifunctional microplate reader; wherein, when MXene / In / PDA-300 was added and cultured for 24 hours, the cells were subjected to both laser irradiation and non-laser irradiation conditions, respectively. The laser irradiation conditions were as follows: a wavelength of 808 nm, an irradiation time of 10 minutes, and a power density of 1.00 W / cm 2 .

[0075] Table 2 Active oxygen test results

[0076] No laser irradiation With laser irradiation Pure MXene Experiment A: Toxic Experiment B: Toxic MXene / In / PDA-300 Experiment C: Non-toxic Experiment D: Toxic

[0077] The active oxygen level test results of pure MXene are Experiment A and Experiment B.

[0078] The results of Experiment A are as follows Figure 9 As shown, in the absence of laser irradiation, active oxygen is generated in pure MXene;

[0079] The results of Experiment B are as follows Figure 10 As shown in Figure 3, active oxygen is generated in pure MXene under laser irradiation.

[0080] By comparing Experiment A and Experiment B, it can be seen that pure MXene is toxic regardless of the presence of laser irradiation, that is, it does not have the characteristics of near-infrared responsive selective treatment generated by laser responsiveness.

[0081] The active oxygen level test results of MXene / In / PDA-300 are Experiment C and Experiment D.

[0082] The results of Experiment C are as follows Figure 11 As shown, under the condition of no laser irradiation, no active oxygen is generated in MXene / In / PDA-300;

[0083] The results of Experiment D are as follows Figure 12 As shown in the figure, active oxygen is generated in MXene / In / PDA-300 under laser irradiation.

[0084] By comparing Experiment C and Experiment D, it can be seen that MXene / In / PDA-300 is non-toxic when there is no laser irradiation, but is toxic when there is laser irradiation, which means that it has the characteristics of near-infrared responsive selective treatment generated by laser responsiveness;

[0085] In addition, by comparing Experiment A and Experiment C, it can be seen that after the pure MXene surface was loaded with In nanoparticles and coated with PDA, the toxicity of pure MXene was successfully removed without laser irradiation;

[0086] At the same time, by comparing Experiment B and Experiment D, it can be seen that after the pure MXene surface is loaded with In nanoparticles and coated with PDA, the toxicity of pure MXene is enhanced under laser irradiation.

[0087] In order to demonstrate the effect of indium chloride addition on performance, that is, In plays a role in the technical solution, Examples 2 and 3 are provided, in which MXene / In / PDA photothermal composite materials are prepared with indium chloride additions of 50% and 66%, respectively.

[0088] Example 2

[0089] A method for preparing a MXene / In / PDA photothermal composite material with an indium chloride addition amount of 66%. The steps not specifically described are the same as those in Example 1, except that: in step 3, the amount of indium chloride added is 0.01 g. The obtained material is referred to as MXene / In / PDA-100.

[0090] The XRD test results of MXene / In / PDA-100 are as follows: Figure 1 As shown in Figure 3, the spectra of MXene / In / PDA-100 and MXene / In / PDA-300 are similar. The test results show that MXene / In / PDA-100 and MXene / In / PDA-300 have the same composition and crystal structure.

[0091] The TEM test results of MXene / In / PDA-100 are as follows: Figure 7 As shown in Figure 3, MXene / In / PDA-100 and MXene / In / PDA-300 have similar micromorphologies.

[0092] The photothermal performance test results of MXene / In / PDA-100 are as follows: Figure 4 As shown,

[0093] At a power density of 0.25 W / cm 2 When , the highest photothermal conversion temperature is 34.0℃;

[0094] At a power density of 0.51 W / cm 2 When , the highest photothermal conversion temperature is 41.9℃;

[0095] At a power density of 1.00 W / cm 2 The highest photothermal conversion temperature is 46.7℃.

[0096] Example 3

[0097] A method for preparing a MXene / In / PDA photothermal composite material with an indium chloride addition amount of 75%. The steps not specifically described are the same as those in Example 1, except that: in step 3, the amount of indium chloride added is 0.02 g. The obtained material is referred to as MXene / In / PDA-200.

[0098] The XRD test results of MXene / In / PDA-200 are as follows: Figure 1 As shown in Figure 3, the spectra of MXene / In / PDA-200 and MXene / In / PDA-300 are similar. The test results show that MXene / In / PDA-200 and MXene / In / PDA-300 have the same composition and crystal structure.

[0099] The TEM test results of MXene / In / PDA-200 are as follows Figure 7 As shown in the figure, MXene / In / PDA-200 and MXene / In / PDA-300 have similar morphological structures.

[0100] The photothermal performance test results of MXene / In / PDA-200 are as follows: Figure 4 As shown,

[0101] At a power density of 0.25 W / cm 2 When the maximum photothermal conversion temperature is 37.8℃;

[0102] At a power density of 0.51 W / cm 2 When the maximum photothermal conversion temperature is 46.5℃;

[0103] At a power density of 1.00 W / cm 2 The highest photothermal conversion temperature is 53.6℃.

[0104] Combining the XRD, TEM and photothermal performance test results of Example 1, Example 2 and Example 3, it can be seen that the amount of indium chloride added is in the range of 50%-75%:

[0105] 1. No effect on the composition and crystal structure of MXene / In / PDA photothermal composite materials;

[0106] 2. It has no effect on the micromorphology of MXene / In / PDA photothermal composite materials;

[0107] 3. It forms a positive correlation with the photothermal properties of MXene / In / PDA photothermal composite materials;

[0108] Therefore, the addition of indium chloride directly and only affects the photothermal performance. The photothermal conversion temperature is lowest when the addition is 50%, and the photothermal conversion temperature is highest when the addition is 75%. The addition of indium chloride does not affect the morphology and structure of the material itself.

Claims

1. A method for preparing a MXene / In / PDA photothermal composite material, characterized in that The following steps are involved: Step 1, preparation of MXene, LiF is completely dissolved in HCl solution to obtain solution A, then Ti3AlC2 is slowly added to solution A, and an etching reaction is carried out under stirring conditions to etch the Al layer in Ti3AlC2. Finally, the obtained product is centrifuged and washed with deionized water until the supernatant is neutral and freeze-dried to obtain Ti3C2T x , namely MXene; Step 2, simultaneous in situ preparation of In and PDA. After ultrasonically dispersing the MXene obtained in step 1 in ethanol, sodium citrate and indium chloride solutions are added and ultrasonication is continued to obtain solution B. At the same time, dopamine is added to tris(hydroxymethylaminomethane) hydrochloride solution to obtain solution C. Then, solution B and solution C are mixed and ultrasonically reacted under certain conditions. Finally, the obtained product is alternately washed with water and ethanol and freeze-dried to obtain a MXene / In / PDA photothermal composite material, referred to as MXene / In / PDA-300.

2. The preparation method according to claim 1, wherein: In step 1, the molar ratio of LiF to Ti3AlC2 is 9.5:1; and the reaction time is 24 h.

3. The preparation method according to claim 1, wherein: In step 2, the molar ratio of MXene, sodium citrate, and indium chloride is 12:23:27; in step 2, the pH of the tris(hydroxymethyl)aminomethane hydrochloride) solution is 8.5; and in step 2, the ultrasonic reaction time is 6 hours.

4. The preparation method according to claim 1, wherein: The obtained MXene / In / PDA photothermal composite material is composed of MXene, In nanoparticles and PDA. In nanoparticles and PDA are in situ loaded on MXene, and the obtained MXene / In / PDA exhibits a rough flaky morphology. The MXene plays two roles in the technical solution: one is as a photosensitizer when realizing the photodynamic therapy PDT function, and the other is as a carrier when realizing the photothermal therapy PTT and PDT functions, that is, realizing the combined treatment of PTT and PDT; The role of the In nanoparticles in the technical solution is to provide a photothermal effect, that is, to generate heat under laser irradiation to kill cancer cells; The role of the PDA in the technical solution is to remove the toxicity of pure MXene and provide biocompatibility.

5. The preparation method according to claim 1, wherein: The obtained MXene / In / PDA photothermal composite material has photothermal properties for tumor treatment at a power density of 0.25-1W / cm 2 When the temperature is within the range of , the highest photothermal conversion temperature is 38-62℃; It has stable performance in light-heat cycle. In the light-heat test of 5 cycles, the temperature difference between the highest temperature and the lowest temperature is less than 5℃. It has therapeutic selectivity, that is, it has the characteristics of near-infrared response and produces toxic reactive oxygen species ROS under laser irradiation.

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