Preparation method and application of targeted nanocomposite materials

Abstract

The present invention provides a method for preparing a targeted nanocomposite material, comprising titanium peroxide loaded on the surface of cuttlefish ink nanoparticles. This method prepares cuttlefish ink nanoparticles (CINPs), a natural nanomaterial with excellent photothermal effects. Titanium peroxide (PTC), which can generate a large amount of reactive oxygen species (ROS), is loaded onto the CINPs. The CINPs are then coated with hyaluronic acid (HA) to target tumor cells, achieving targeted photothermal therapy for tumors.

Description

Technical Field

[0001] The present invention relates to the field of biomedicine technology, and more particularly to a preparation method of a targeted nanocomposite material and its application. Background Art

[0002] In recent years, photothermal therapy (PTT) has become an effective and important approach for cancer treatment. This is primarily due to its short treatment time (approximately a few minutes), minimal invasiveness, significant efficacy, and minimal side effects. PTT is a typical photon-triggered therapy modality that kills tumor cells through localized hyperthermia generated by photothermal agents under the stimulation of visible or near-infrared light (600-900 nm). Cancer cells are more sensitive to hyperthermia than normal cells, and hyperthermia can cause irreversible damage to cancer cell membranes and promote protein denaturation. To optimize drug efficacy, synthetic nanoparticles have been actively developed. Furthermore, due to the immune evasion of tumor cells, other anti-tumor drugs, such as photothermal agents, which can both directly kill tumor cells and generate tumor-associated antigens in situ, have been incorporated into synthetic nanoparticles to enhance anti-tumor immune responses. Photothermal agents are a key component in PTT applications, converting light energy directly into heat through non-radiative mechanisms, resulting in hyperthermia ablation of diseased tissue or cells. Many different types of photothermal agents have been reported, including inorganic and organic nanomaterials. Early research on photothermal agents focused primarily on precious metal nanomaterials, which possess excellent light absorption capabilities and high photothermal conversion efficiency. However, expensive reagents and complex preparation processes are prerequisites for synthesizing nanoparticles, limiting their further application. Squid ink, a black suspension of natural nanoparticles, is often thought to protect cuttlefish from predators by spraying and forming a visual smoke screen. Currently, due to its rich nutritional content and diverse biological properties, such as hemostatic, antibacterial, and anti-radiation effects, it is widely used in food, art, and medicine. From a chemical perspective, CINPs are primarily composed of melanin and a small amount of amino acids and monosaccharides. They have a spherical shape, high dispersibility, and good biocompatibility. Furthermore, due to the photothermal conversion properties of melanin itself, CINPs exhibit excellent photothermal conversion capacity and photothermal stability.

[0003] Chemodynamic therapy (CDT) is a new type of tumor treatment technology based on the iron-based Fenton reaction. 2+ 、Cu 2+ and Mn 2+etc.) promotes the catalytic reaction with H2O2 to produce highly active and toxic ·OH, which is used for cancer treatment. However, this Fenton or Fenton-like reaction is heavily dependent on the H2O2 concentration, and the H2O2 concentration in TME is not enough to achieve the ideal therapeutic effect. In recent years, peroxide titanium complex (PTC) has been studied by domestic scholars as a reaction intermediate. PTC can exist stably under physiological conditions and can decompose at higher temperatures to produce a large amount of ROS. The superoxide radical anion [O2 - ] is an active oxygen with both anionic and free radical characteristics. The most notable feature of peroxide titanium complexes is that they are generated from O2 2- The color reaction is caused by the electronic transition to the metal cation.

[0004] Hyaluronan is a large polysaccharide composed of repeating disaccharides of glucuronic acid and acetylglucosamine, which regulates cell adhesion, migration, and proliferation by interacting with specific cell surface receptors: CD44 and the receptor for HA-mediated motility (RHAMM).

[0005] Therefore, how to combine cuttlefish ink (CINPs), titanium peroxide and hyaluronic acid is the key to the present invention. Summary of the Invention

[0006] The present invention provides a preparation method and application of a targeted nanocomposite material. By preparing a natural nanomaterial, cuttlefish ink nanoparticles (CINPs), which has good photothermal effect, titanium peroxide (PTC) that can additionally generate a large amount of reactive oxygen species (ROS) is loaded on the surface of the CINPs, and finally coated with hyaluronic acid (HA) to target tumor cells, tumor-targeted photothermal therapy is achieved.

[0007] According to one aspect of the present invention, a method for preparing a targeted nanocomposite material is provided. The targeted nanocomposite material comprises loading titanium peroxide on the surface of squid ink nanoparticles.

[0008] Preferably, based on the above scheme, a method for preparing a targeted nanocomposite material of the present invention comprises the following steps:

[0009] Step 1, obtaining squid ink nanoparticles and dispersing them in deionized water to form a CINPs solution;

[0010] Step 2: Polyvinyl pyrrolidone is evenly dispersed in the CINPs solution obtained in step 1, and 5% titanium sulfate solution and 10 mol / L hydrogen peroxide solution are added respectively, stirred evenly, and ammonia water is added dropwise to adjust the pH to neutral. After the reaction, the mixture is allowed to stand and then centrifuged to obtain a dispersion of CINPs@PTC nanoparticles.

[0011] Preferably, based on the above scheme, the method further comprises uniformly dispersing the hyaluronic acid solution in the CINPs@PTC solution obtained in step 2, stirring at room temperature, and centrifuging to obtain CINPs@PTC@HA.

[0012] Preferably, based on the above scheme, the mass ratio of the hyaluronic acid solution to CINPs@PTC is 20:1.

[0013] Preferably, based on the above scheme, in step 2, the mass ratio of CINPs to Ti is 1:1.

[0014] Preferably, based on the above scheme, in step 2, the CINPs solution and polyvinyl pyrrolidone are stirred at room temperature for 15 minutes at a rotation speed of 600 r / min.

[0015] The invention also provides a targeted nano-composite material of cuttlefish ink loaded with titanium peroxide prepared by the method.

[0016] The present invention also provides a use of the targeted nanocomposite material, CINPs@PTC@HA, as a therapeutic drug in biological imaging.

[0017] The present invention also provides a use of the targeted nanocomposite material, namely CINPs@PTC@HA, as a therapeutic drug in tumor treatment.

[0018] The preparation method of a targeted nanocomposite material of the present invention has the following advantages and

[0019] Beneficial effects:

[0020] (1) The cuttlefish ink nanoparticles (CINPs) of the present invention are naturally occurring melanin-rich nanoparticles. Compared with other synthetic photothermal agents, they have higher biosafety, biodegradability, and are easily functionalized, while retaining their excellent photothermal performance and photothermal conversion efficiency. Furthermore, the smaller size of the nanomaterials can promote high permeability and retention effects in solid tumors.

[0021] (2) The titanium peroxide (PTC) of the present invention is not restricted by these factors and can generate a large amount of active oxygen under light. Combined with photothermal therapy, it has a high killing ability against tumor cells and achieves a good therapeutic effect.

[0022] (3) The present invention coats a layer of hyaluronic acid (HA) on the outer layer of the CINPs@PTC composite nanomaterial, which has the performance of targeted tumor treatment to achieve better therapeutic effects.

[0023] (4) Unlike the current materials with only a single property, the CINPs@PTC@HA composite nanomaterial in the present invention not only has excellent PTT performance, but also can produce more ROS in response to light, and has a good tumor treatment effect. BRIEF DESCRIPTION OF THE DRAWINGS

[0024] In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the following briefly introduces the drawings required for describing the embodiments. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without inventive efforts. In the drawings:

[0025] Figure 1 This is a scanning transmission electron microscopy image of CINPs@PTC@HA in Example 1 of the present invention.

[0026] Figure 2 This is a photothermal heating effect curve of different concentrations of CINPs@PTC@HA in Example 1 of the present invention.

[0027] Figure 3 This is the ESR spectrum of CINPs@PTC@HA in Example 1 of the present invention.

[0028] Figure 4-1 This is a comparison chart of the cytotoxicity test results of different reagents in Example 1 of the present invention.

[0029] Figure 4-2 This is a graph showing the cell survival rate of fibroblasts in Example 1 of the present invention.

[0030] Figure 5 This is a fluorescence imaging diagram of the ability of different reagents to generate ROS when co-incubated with 4T1 cells in Example 1 of the present invention.

[0031] Figure 6 This is a live-dead staining data diagram of 4T1 cells co-incubated with different reagents and illuminated in Example 1 of the present invention.

[0032] Figure 7 This is an in vivo imaging diagram of the mouse of the present invention.

[0033] Figure 8 This is the in vivo photothermal imaging image of mice according to the present invention.

[0034] Figure 9 This is a diagram showing the changes in tumor volume after treatment with different agents of the present invention.

[0035] Figure 10 This is a graph showing the weight changes of mice after treatment with different agents of the present invention.

[0036] Figure 11Images were taken of tumor volumes after treatment with different agents of the present invention. DETAILED DESCRIPTION

[0037] The following embodiments of the present invention are described in further detail with reference to the accompanying drawings and examples. The following examples are used to illustrate the present invention but are not intended to limit the scope of the present invention.

[0038] It will be understood that when used in this specification and the appended claims, the term "comprising" indicates the presence of described features, integers, steps, operations, elements and / or components, but does not preclude the presence or addition of one or more other features, integers, steps, operations, elements, components and / or collections.

[0039] To simplify the drawings, only the parts relevant to the present invention are schematically shown in each figure. They do not represent the actual structure of the product. Furthermore, to simplify the drawings and facilitate understanding, in some figures, only one of the components with the same structure or function is schematically depicted or labeled. As used herein, "one" not only means "only one" but also "more than one."

[0040] It should be further understood that the term "and / or" used in this specification and the appended claims refers to and includes any and all possible combinations of one or more of the associated listed items.

[0041] In the embodiments shown in the accompanying drawings, directional indications (such as up, down, left, right, front, and rear) used to explain the structure and movement of various components of the present invention are not absolute but relative. These descriptions are applicable when the components are in the positions shown in the accompanying drawings. If the descriptions of the positions of these components are changed, the directional indications will also change accordingly.

[0042] In addition, in the description of the present application, the terms "first", "second", etc. are only used to distinguish the description and cannot be understood as indicating or implying relative importance.

[0043] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the specific embodiments of the present invention will be described below with reference to the accompanying drawings. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings and other embodiments can be obtained based on these drawings without inventive work.

[0044] See also Figure 1 , and combined with Figure 2 and Figure 3 As shown, the preparation method of a targeted nanocomposite material of the present invention comprises the following steps:

[0045] Step 1: Extracting a solution containing CINPs from an ink sac of fresh cuttlefish. First, perform low-speed centrifugation to remove large particles, then perform high-speed centrifugation to obtain CINPs. The CINPs are then washed by centrifugation with deionized water to obtain cuttlefish ink nanoparticles, which are then dispersed in deionized water to form a CINPs solution.

[0046] Step 2: Polyvinyl pyrrolidone is uniformly dispersed in the CINPs solution obtained in step 1, and a 5% titanium sulfate solution and a 10 mol / L hydrogen peroxide solution are added respectively. Ammonia water is added dropwise to the CINPs dispersion under constant stirring, and the pH is adjusted to neutral. The mixture is reacted for a certain period of time, and then allowed to stand and centrifuged to remove unreacted PVP. The mixture is then washed to obtain a dispersion of nanoparticles CINPs@PTC.

[0047] Step 3: The hyaluronic acid solution is uniformly dispersed in the CINPs@PTC solution obtained in step 2, stirred at room temperature for a certain period of time, centrifuged, and washed with deionized water to obtain CINPs@PTC@HA.

[0048] The mass ratio of CINPs to Ti was 1:1, and the mass ratio of hyaluronic acid solution to CINPs@PTC was 20:1.

[0049] In step 2, ammonia water is added dropwise into the CINPs dispersion under constant stirring, the pH is adjusted to 6.8-7.2, and the mixture is allowed to react for a certain period of time. After standing, the mixture is centrifuged to remove unreacted PVP and washed with deionized water to obtain nanoparticles CINPs@PTC. When adjusting the pH, the ammonia water used needs to be diluted 10 times.

[0050] In the present invention, the squid ink CINPs and polyvinyl pyrrolidone PVP are stirred at room temperature for 15 minutes at a rotation speed of 600 r / min; after the pH is adjusted to 7, the stirring time is 1 hour and the standing time is 2 hours.

[0051] In step 3, the specific steps are: adding the hyaluronic acid solution dropwise to the CINPs@PTC solution at a mass ratio of 20:1 under high-speed stirring, stirring at room temperature for 24 hours, centrifuging at 12000, washing with deionized water twice, and redispersing the product in deionized water to obtain a dispersion of CINPs@PTC@HA nanoparticles.

[0052] In order to verify the effect of the present invention, the following will use specific examples and experimental data tests to illustrate its effect.

[0053] Example 1

[0054] The method for preparing a targeted nanocomposite material of cuttlefish ink loaded with titanium peroxide of the present invention comprises the following specific steps:

[0055] (1) Preparation of CINPs:

[0056] Freshly purchased squid were dissected and the ink sac removed. The liquid within the ink sac was extracted to obtain a solution containing CINPs. This solution was then centrifuged at 2000 rpm for 5 minutes to remove large particles. The solution was then centrifuged at 12000 rpm for 10 minutes at 4°C to obtain the CINPs. Finally, the solution was washed three times with deionized water (DI water) and suspended in DI water for later use.

[0057] (2) Preparation of CINPs@PTC

[0058] Weigh 0.1g of titanium sulfate and dissolve it in 2.1mL of sulfuric acid to obtain a 5% titanium sulfate solution. Weigh 0.5g of polyvinyl pyrrolidone and disperse it in the prepared CINPs. After stirring for 15 minutes, add 0.7mL of the 5% titanium sulfate solution, followed by 0.2mL of 10mol / L hydrogen peroxide and dropwise addition of ammonia while stirring continuously. Adjust the pH to approximately 7, wash the mixture three times with deionized water, and finally disperse it in deionized water to obtain the CINPs@PTC solution for later use.

[0059] (2) Preparation of CINPs@PTC@HA:

[0060] Prepare a 10 mg / mL hyaluronic acid solution and add dropwise the dispersion of CINPs@PTC nanoparticles obtained in (2), stir at room temperature for 24 h, centrifuge at 12000 r / min, wash three times with deionized water, and redisperse the washed nanoparticles in deionized water to obtain a dispersion of the composite nanomaterial CINPs@PTC@HA, which is stored in a refrigerator at 4°C for use.

[0061] The morphology of CINPs@PTC@HA in Example 1 was observed under a scanning transmission electron microscope. The specific steps are as follows:

[0062] First, the prepared CINPs@PTC@HA liquid sample was ultrasonically dispersed into a uniform suspension. The powder solution was placed on the copper mesh surface by droplet method and dried. The powder sample was evenly distributed on the copper mesh and free of contaminants. The copper mesh was gently blown with an ear bulb to ensure that there was no easily falling powder. The scanning transmission electron microscope was used to find a suitable field of view for photography. The scanning transmission electron microscope results are shown in the attached figure. Figure 1 shown.

[0063] According to the attached Figure 1Scanning transmission electron microscopy results show that the CINPs@PTC@HA nanoparticles are approximately 200 nm in size. The CINPs are spherical, while the PTC particles are darker, spherical particles attached to the CINPs' surface. A layer of transparent film-like material can be seen on the outside of the nanoparticles, demonstrating successful HA encapsulation. The CINPs@PTC@HA exhibit a uniform overall morphology and good dispersion.

[0064] The photothermal heating capacity of CINPs@PTC@HA at different concentrations in Example 1 was tested as follows:

[0065] First, 1 mL of CINPs@PTC@HA nanoparticle dispersions with different concentrations were taken and the samples were irradiated with an 808 nm laser (2 W / cm 2 ) Use a thermal imager to record the real-time temperature changes of the heating process every 10 seconds. The test results are shown in the attached Figure 2 shown.

[0066] Test results show that the higher the concentration of the CINPs@PTC@HA solution, the higher the temperature rise, showing a concentration-dependent temperature rise. This indicates that CINPs@PTC@HA has a good photothermal effect and shows great potential as a natural photothermal agent in tumor photothermal therapy.

[0067] The CINPs@PTC@HA in Example 1 was subjected to ESR testing using the following method:

[0068] First, take 30 μL of CINPs@PTC@HA, add 30 μL of DMPO (100 mM methanol as solvent), mix well, and then use a capillary to draw a certain amount of the mixture. After putting it into a quartz tube, put it into the EPR sample chamber to test superoxide free radicals. The test results are shown in the attached figure. Figure 3 shown.

[0069] according to Figure 3 The test results show that the CINPs@PTC@HA nanomaterial has no free radical signal in the dark, but a vacancy signal peak appears. After 30 minutes of illumination, a free radical signal peak appears, and the vacancy peak and free radical peak overlap. Based on the free radical signal peak, it can be determined that the free radical is a superoxide radical.

[0070] The CINPs@PTC@HA in Example 1 was subjected to a cytotoxicity test using the following method:

[0071] 4T1 cells were selected as in vitro research subjects, and all cells were cultured in a humidified atmosphere incubator at 37°C and 5% CO2. The experiment was divided into five groups, four of which were illumination groups and one was a non-illumination group. The illumination groups were respectively incubated with CINPs@HA nanoparticle solution, CINPs@PTC@HA nanoparticle solution, CINPs@PTC nanoparticle solution, and PTC@HA nanoparticle solution at concentrations of 0 μg / mL, 25 μg / mL, 50 μg / mL, 100 μg / mL, and 200 μg / mL in Example 1; the non-illumination groups were respectively incubated with CINPs@PTC@HA nanoparticle solution at concentrations of 0 μg / mL, 25 μg / mL, 50 μg / mL, 100 μg / mL, and 200 μg / mL in 4T1 cells, and then the cells were illuminated with an 808 nm near-infrared laser (2 W / cm 2 ) irradiated 4T1 cells for 5 min. Cytotoxicity was determined using MTT.

[0072] The test results are as follows Figure 4-1 As shown, the test results show that under laser irradiation, CINPs@PTC@HA nanoparticle solution and CINPs@PTC nanoparticle solution can effectively kill 4T1 cells, among which CINPs@PTC@HA nanoparticle solution has the most obvious killing effect.

[0073] To further verify the biosafety of the material, mouse embryonic fibroblasts (3T3) were used as normal cells to detect the cytotoxicity of CINPs@PTC@HA. All cells were cultured in a humidified atmosphere incubator at 37°C and 5% CO2. 3T3 cells were incubated with CINPs@PTC@HA nanoparticle dispersions at concentrations of 0 μg / mL, 25 μg / mL, 50 μg / mL, 100 μg / mL, and 200 μg / mL, respectively, and the cytotoxicity was determined using MTT.

[0074] The test results are as follows: Figure 4-2 As shown, the test results showed that the survival rate of 3T3 cells was above 80%, indicating that CINPs@PTC@HA has good biosafety.

[0075] The CINPs@PTC@HA in Example 1 was subjected to intracellular reactive oxygen species detection, and the test method was as follows:

[0076] A total of four groups of experiments were set up, one of which was PBS solution without additives, and three groups of PBS solutions were added with 200 μg / mL CINPs and CINPs@PTC@HA nanoparticles, respectively, and incubated with 4T1 cells for 6 hours, stained with 10 μM DCFH-DA, and incubated in the dark for 25 minutes. Then, one group of CINPs@PTC@HA was taken for illumination, and then ROS detection was performed using fluorescence confocal microscopy.

[0077] The test results are as follows Figure 5 As shown, the test results showed that the Control group and the CINPs group had almost no green fluorescence, the CINPs@PTC@HA non-illumination group had a lighter green fluorescence, and the CINPs@PTC@HA illumination group showed stronger green fluorescence, indicating that CINPs@PTC@HA can produce more ROS under near-infrared light irradiation.

[0078] The CINPs@PTC@HA in Example 1 was subjected to a live-dead staining experiment, and the experimental method was as follows:

[0079] Calcein-AM and PI staining were used to observe the cell viability of 4T1 cells. The experiment was divided into four groups: (1) PBS; (2) CINPs; (3) CINPs+Laser; (4) CINPs@PTC@HA; (5) CINPs@PTC@HA+Laser. 4T1 cells were incubated with 200 μg / mL CINPs and CINPs@PTC@HA for 6 h, and then the illumination group was illuminated by 808 nm laser (2 W / cm 2 After incubation for another 6 h, the cells were stained with Calcein-AM and PI in PBS for 30 min, washed thoroughly with PBS, and observed under a laser confocal microscope.

[0080] The test results are as follows: Figure 6 shown.

[0081] The test results showed that nearly all 4T1 cells in the PBS and CINPs groups were stained green, while some cells in the CINPs light-exposed groups and CINPs@PTC@HA were stained red. In contrast, all cells in the CINPs@PTC@HA light-exposed group were stained red, indicating cell death. These results were consistent with those of the MTT assay, demonstrating that the CINPs@PTC@HA nanomaterial has a strong ability to kill tumor cells.

[0082] The CINPs@PTC@HA in Example 1 was subjected to an in vivo living imaging experiment. The experimental method is as follows:

[0083] 4T1 tumor cells (1.2×10 64T1 tumor transplantation model was established by subcutaneous injection of 4T1 into the right flank of BALB / c mice. 3 Cy5-labeled CINPs@PTC and CINPs@PTC@HA were injected into tumor-bearing mice (n=3) via the tail vein at a dose of 6 mg / mL. In vivo imaging was performed using an IVIS imaging system at predetermined time intervals (0, 2, 4, 6, 8, 10, and 12 hours) after injection, assessing drug distribution in real time by measuring changes in fluorescence distribution within the mice. Seventy-two hours after intravenous injection, tumor tissue and major organs, including the heart, liver, spleen, lungs, and kidneys, were harvested for stereofluorescence imaging analysis.

[0084] The test results are as follows: Figure 7 As shown. Test results showed that the CINPs@PTC group did not accumulate significantly in the mouse tumor site, while the CINPs@PTC@HA group clearly accumulated in the mouse tumor site throughout the monitoring period and was concentrated in the tumor site 12 hours after drug injection, indicating that the HA-coated CINPs@PTC nanomaterial has excellent tumor targeting ability. In addition, fluorescence imaging of organs in vitro showed that 72 hours after injection of the tumor-targeting CINPs@PTC@HA drug, the fluorescence intensity at the tumor site was significantly higher than that of other organ tissues, indicating that CINPs@PTC@HA has excellent tumor targeting ability for solid tumors in vivo.

[0085] The therapeutic effect of CINPs@PTC@HA in Example 1 was tested in a BALB / c mouse subcutaneous tumor model. The testing method was as follows:

[0086] BALB / c mice were divided into five groups: (1) PBS, (2) CINPs@PTC@HA, (3) CINPs@PTC+Laser, (4) CINPs@HA+Laser, and (5) CINPs@PTC@HA+Laser. The mice were injected with nanoparticles through the tail vein. Twelve hours later, the mice were exposed to 808 nm laser (2 W / cm 2 ) for 6 minutes of light treatment. During the treatment, a thermal imager was used to monitor the temperature of the mouse tumor site in real time, and the temperature was recorded every 1 minute. The photothermal imaging of the mouse tumor site is shown in the attached figure. Figure 8 shown.

[0087] The test results show that under near-infrared light irradiation, the CINPs@PTC@HA nanomaterial group exhibited a significantly enhanced thermal effect, reaching around 55°C, and had effective killing ability against tumor cells.

[0088] The mice were weighed and their tumor volumes were measured before light treatment, and every other day after the light treatment. Figure 9 、 10 shown.

[0089] After the treatment, the tumor tissue of the mice was taken for volume measurement. The test results were as follows: Figure 11 shown.

[0090] The results of the therapeutic effect test showed that CINPs@PTC@HA nanomaterial had the best therapeutic effect and had good biosafety when combined with photothermal therapy.

[0091] Compared with the prior art, the present invention has the following advantages and beneficial effects:

[0092] (1) Among near-infrared light-responsive nanomaterials, inorganic nanomaterials, such as gold nanoparticles and plasmonic metal clusters, have unclear long-term biocompatibility. Some small molecule photosensitizers, such as indocyanine green (ICG) and chlorin e6 (Ce6), have poor stability and show significant degradation after near-infrared light irradiation. Cuttlefish ink nanoparticles (CINPs) are naturally occurring melanin-rich nanoparticles that, compared with other synthetic photothermal agents, have higher biosafety, biodegradability, and are easily functionalized, while retaining their excellent photothermal performance and photothermal conversion efficiency. Furthermore, the smaller size of nanomaterials can promote high permeability and retention in solid tumors.

[0093] (2) CDT treatment is restricted by various factors such as H2O2 concentration, excessive content of reducing substances, and catalytic activity of metals. Traditional CDT materials such as Fe3O4 have low responsiveness in the slightly acidic environment of tumors, which will limit the efficiency of OH production. Titanium peroxide (PTC) is not restricted by these factors and can generate a large amount of reactive oxygen species under light. Combined with photothermal therapy, it has a high killing ability against tumor cells and achieves good therapeutic effects.

[0094] (3) The present invention coats a layer of hyaluronic acid (HA) on the outer layer of the CINPs@PTC composite nanomaterial, which has the performance of targeted tumor treatment to achieve better therapeutic effects.

[0095] (4) Unlike the current materials with only a single property, the CINPs@PTC@HA composite nanomaterial in the present invention not only has excellent PTT performance, but also can produce more ROS in response to light, and has a good tumor treatment effect.

[0096] Finally, the method of this application is only a preferred embodiment and is not intended to limit the scope of protection of the present invention. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principles of the present invention should be included in the scope of protection of the present invention.

Claims

1. A method for preparing a targeted nanocomposite material, characterized in that: The targeted nanocomposite material comprises titanium peroxide loaded on the surface of squid ink nanoparticles, comprising the following steps: Step 1, obtaining squid ink nanoparticles and dispersing them in deionized water to form a CINPs solution; Step 2: Polyvinyl pyrrolidone is uniformly dispersed in the CINPs solution obtained in step 1, and a 5% titanium sulfate solution and a 10 mol / L hydrogen peroxide solution are added respectively, stirred evenly, and ammonia water is added dropwise to adjust the pH to neutral. After the reaction, the mixture is allowed to stand and then centrifuged to obtain a dispersion of CINPs@PTC nanoparticles; The method further includes uniformly dispersing the hyaluronic acid solution in the CINPs@PTC solution obtained in step 2, stirring at room temperature, and centrifuging to obtain CINPs@PTC@HA.

2. The method for preparing a targeted nanocomposite material according to claim 1, wherein: The mass ratio of the hyaluronic acid solution to CINPs@PTC is 20:

1.

3. The method for preparing a targeted nanocomposite material according to claim 1, wherein: In step 2, the mass ratio of CINPs to Ti was 1:

1.

4. The method for preparing a targeted nanocomposite material according to claim 1, wherein: In step 2, the CINPs solution and polyvinyl pyrrolidone were stirred at room temperature for 15 min at a rotation speed of 600 r / min.

5. A targeted nanocomposite material of cuttlefish ink loaded with titanium peroxide prepared by the method of claim 1.

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