WO2019184201A1 - 基于钛量子点的纳米钛光热制剂及其制备方法 - Google Patents
基于钛量子点的纳米钛光热制剂及其制备方法 Download PDFInfo
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Definitions
- the invention relates to the field of biomedical nano materials, in particular to a nanometer titanium photothermal preparation based on titanium quantum dots and a preparation method thereof.
- Near-infrared phototherapy based on nanomaterials is a new type of potential therapy, especially near-infrared light-responsive photothermal therapy, which solves the problem that light waves are easily absorbed, easily scattered, and have nucleic acids in short-wavelength phototherapy such as ultraviolet light and visible light. Toxicity, as well as poor tissue penetration.
- the near-infrared light has a wavelength of about 700-1000 nm and has the advantages of low absorption and high penetration (more than 1 cm).
- conventional photothermal therapy materials mainly include gold nanoparticles, carbon nanotubes, graphene and the like.
- existing photothermal materials often fail to balance photothermal conversion efficiency and biocompatibility.
- the present invention provides a titanium quantum dot-based nano titanium photothermal preparation, wherein the titanium quantum dot-based nano titanium photothermal preparation has high photothermal conversion efficiency, good biocompatibility, and safety. Poison and other advantages, can be used for photothermal therapy including tumors.
- a first aspect of the invention provides a titanium quantum dot-based nanotitanium photothermal formulation comprising titanium quantum dots.
- the size of the titanium quantum dots is less than or equal to 20 nm.
- the size of the titanium quantum dots is 1-10 nm.
- the size of the titanium quantum dots is 10-20 nm.
- the size of the titanium quantum dots is 1-5 nm.
- the size of the titanium quantum dot is 2-3 nm.
- the nano titanium photothermal preparation further comprises a biocompatible material coated on the surface of the titanium quantum dot.
- the biocompatible material comprises hyaluronic acid, dextran and derivatives thereof, chitosan and derivatives thereof, pectin, carboxymethyl cellulose, albumin, liposome, cell membrane, polyethylene One or more of pyrrolidone, polylactic acid-glycolic acid copolymer, polyethyleneimine, polyacrylic acid, and polyethylene glycol and derivatives thereof.
- the polyethylene glycol and its derivative have a molecular weight of between 200 and 20,000.
- biocompatible material is adsorbed on the surface of the titanium quantum dot by electrostatic action.
- the mass ratio of the titanium quantum dots to the biocompatible material is 1:1-10.
- the nanotitanium photothermal preparation further comprises a targeting material attached to the titanium quantum dot by a chemical bond or attached to the biocompatible material.
- the targeting material is folic acid, and the folic acid is attached to the polyethylene glycol via an amide bond.
- the nano titanium photothermal preparation provided by the first aspect of the invention has high photothermal conversion efficiency, good biocompatibility, safety and non-toxicity, and can be used for photothermal therapy including tumors.
- a second aspect of the present invention provides a method for preparing a nano titanium photothermal preparation based on a titanium quantum dot, comprising the following steps:
- the titanium raw material is provided, and the titanium raw material is stripped by a liquid phase stripping method to obtain a titanium quantum dot, that is, a titanium quantum dot-based nano titanium photothermal preparation is obtained.
- liquid phase stripping method specifically comprises the following operations:
- the titanium raw material is added to a polar solvent, and ultrasonically probed for 10-15 hours in an ice bath environment; after the ultrasonication of the probe is finished, ultrasonic bathing is performed, and the ultrasonic bath time is 6-15 h, the temperature of the water bath Maintaining 5-15 ° C; after the end of the ultrasonic bath, centrifugation and drying to obtain titanium quantum dots.
- the polar solvent comprises at least one of isopropyl alcohol, ethanol, water and N-methylpyrrolidone.
- centrifuging operation comprises:
- the preparation method of the nano titanium photothermal preparation further comprises: providing a biocompatible material, mixing the titanium quantum dot with the biocompatible material at 10-30 ° C, stirring for 3-6 h, obtaining Nano titanium photothermal preparation.
- the preparation method of the nano titanium photothermal preparation specifically comprises: dissolving the biocompatible material in an appropriate amount of the first solvent to obtain a biocompatible material solution, and dispersing the titanium quantum dot in an appropriate amount.
- a titanium quantum dot dispersion is obtained, and the biocompatible material solution is mixed with the titanium quantum dot dispersion at 10-30 ° C, and stirred for 3-6 hours to obtain a nano titanium photothermal preparation.
- the second aspect of the invention provides a preparation method of a nanometer titanium photothermal preparation based on titanium quantum dots, the preparation method is simple and easy to operate, and the prepared nano titanium photothermal preparation has high light-heat conversion efficiency and good biocompatibility.
- the titanium quantum dot-based nano titanium photothermal preparation provided by the invention has high photothermal conversion efficiency, good biocompatibility, safety and non-toxicity, and can be used for photothermal therapy including tumors;
- the preparation method of the nano titanium photothermal preparation provided by the invention is simple and easy to operate.
- Example 1 is a transmission electron micrograph of a titanium quantum dot prepared in Example 1;
- Figure 4 is a photograph of different concentrations of titanium quantum dot aqueous dispersion
- Figure 5 is an absorption spectrum diagram of different concentrations of titanium quantum dot aqueous dispersion
- Figure 6 is an extinction coefficient of a titanium quantum dot
- Figure 7 is a temperature rise curve of different concentrations of titanium quantum dot aqueous dispersion
- Figure 8 is a photothermal conversion efficiency of a titanium quantum dot aqueous dispersion
- Figure 9 is a graph showing the results of cytotoxicity measurement of titanium quantum dots
- Figure 10 is a graph showing the killing effect of the photothermal effect of titanium quantum dots on cancer cells
- Figure 11 is a graph showing the effect of the photothermal effect of titanium quantum dots on cancer treatment.
- titanium quantum dots or "titanium” referred to in the present invention means, unless otherwise specified, elemental titanium.
- a first aspect of an embodiment of the present invention provides a titanium quantum dot-based nano titanium photothermal preparation comprising titanium quantum dots.
- the size of the titanium quantum dots is less than or equal to 20 nm.
- the titanium quantum dots have a size of 1-10 nm.
- the titanium quantum dots have a size of 10-20 nm.
- the titanium quantum dots have a size of 1-5 nm.
- the titanium quantum dots have a size of 2-3 nm.
- the size of the titanium quantum dots is 1 nm, 2 nm, 3 nm, 4 nm, 5 nm, 6 nm, 7 nm, 8 nm, 9 nm, 10 nm, 11 nm, 12 nm, 13 nm, 14 nm, 15 nm, 16 nm, 17 nm, 18 nm, 19 nm. Or 20nm.
- the number of layers of the titanium quantum dots is not particularly limited.
- the "size" of a titanium quantum dot as used herein refers to the "diameter" of a titanium quantum dot.
- the titanium quantum dot provided by the embodiment of the invention has a small size, and the small size helps the titanium quantum dot to have a good passive enrichment effect at the tumor site, and is easily discharged from the body, and has good biocompatibility. At the same time, the photothermal effect of the titanium quantum dots is obvious.
- the titanium quantum dots have an absorption from a visible region to a near-infrared region.
- the titanium quantum dots have a light absorption wavelength ranging from 200 to 2000 nm.
- the photothermal conversion efficiency of the titanium quantum dots is greater than or equal to 60%.
- the titanium quantum dots provided by the invention have the advantages of environmental friendliness, biocompatibility, strong absorption of full spectrum and high photothermal conversion efficiency, and have excellent photothermal performance.
- the biocompatible material comprises hyaluronic acid, dextran and derivatives thereof, chitosan and derivatives thereof, pectin, carboxymethyl cellulose, albumin, liposome, One or more of a cell membrane, polyvinylpyrrolidone, polylactic acid-glycolic acid copolymer, polyethyleneimine, polyacrylic acid, and polyethylene glycol and derivatives thereof. Further optionally, the biocompatible material comprises at least one of polyethylene glycol and derivatives thereof, polylactic acid-glycolic acid copolymer, albumin, liposomes, and cell membranes.
- the biocompatible material comprises polyethylene glycol and derivatives thereof, the polyethylene glycol and its derivatives having a molecular weight between 200 and 20,000.
- the end of the polyethylene glycol may be modified by an amino group.
- the biocompatible material is adsorbed on the surface of the titanium quantum dots by electrostatic interaction.
- the nanotitanium photothermal preparation further comprises a targeting material attached to the titanium quantum dot by a chemical bond or attached to the biocompatible material.
- the targeting material is folic acid, and the folic acid is attached to the polyethylene glycol via an amide bond.
- the nano titanium photothermal preparation may be dispersed in physiological saline, phosphate buffer or deionized water for subsequent application.
- the mass ratio of the titanium quantum dot to the biocompatible material is 1:1-10.
- the mass ratio of the titanium quantum dot to the biocompatible material is 1:1, 1:2, 1:3, 1:4, 1:5, 1:6, 1:7, 1 : 8, 1:9 or 1:10.
- the nano titanium photothermal preparation provided by the first aspect of the invention has high photothermal conversion efficiency, good biocompatibility, safety and non-toxicity, and can be used for photothermal treatment including tumors.
- a second aspect of the embodiments of the present invention provides a method for preparing a nanometer titanium photothermal preparation based on a titanium quantum dot, comprising the following steps:
- the titanium raw material is provided, and the titanium raw material is stripped by a liquid phase stripping method to obtain a titanium quantum dot, that is, a titanium quantum dot-based nano titanium photothermal preparation is obtained.
- the titanium raw material is a two-dimensional non-layered metal titanium simple substance, such as titanium powder, such as titanium powder having a particle size of micron order, and specifically may have a particle diameter of about several tens of micrometers or less. Titanium powder. It may also be a titanium block, and its size and shape are not particularly limited. If the titanium raw material is a titanium block having a large particle size, the titanium block may be first ground and ground for liquid phase stripping. The titanium raw material can be obtained by purchase.
- the liquid phase stripping method specifically includes the following operations:
- the titanium raw material is added to a polar solvent, and ultrasonically probed for 10-15 hours in an ice bath environment; after the ultrasonication of the probe is finished, ultrasonic bathing is performed, and the ultrasonic bath time is 6-15 h, the temperature of the water bath Maintaining 5-15 ° C; after the end of the ultrasonic bath, centrifugation and drying to obtain titanium quantum dots.
- the polar solvent comprises at least one of isopropyl alcohol, ethanol, water, and N-methylpyrrolidone (NMP).
- the polar solvent comprises at least one of isopropyl alcohol, ethanol, and N-methylpyrrolidone (NMP).
- the solvent used in the present invention can be used to peel off the titanium raw material to obtain a titanium quantum dot.
- the titanium raw material is present in the solvent at a concentration of from 1 to 7 mg/mL.
- the probe has an ultrasonic power of 250-300W. Further optionally, the ultrasonic power of the probe is 250W, 260W, 270W, 280W, 290W or 300W.
- the probe is sonicated for 10h, 11h, 12h, 13h, 14h or 15h.
- the probe ultrasound is non-continuous ultrasound
- the ultrasonic on/off time is selected to be 2/4 s, ie, ultrasonic for 2 s, then the ultrasound probe is turned off for 4 s, ultrasound is continued for 2 s, and so on.
- the water bath has an ultrasonic power of 350-400W. Further optionally, the water bath ultrasonic power is 350W, 360W, 370W, 380W, 390W or 400W.
- the time of the water bath ultrasound is 10-15 h.
- the time of the water bath ultrasound is 6h, 7h, 8h, 9h, 10h, 11h, 12h, 13h, 14h or 15h.
- the water bath temperature is maintained at 10 °C.
- the centrifugation operation comprises: firstly using a centrifugal force of 5000-8000 g, centrifuging for 20-35 min, taking the supernatant; and then centrifuging the supernatant with a centrifugal force of 10,000-13000 g. At 20-35 min, a precipitate is obtained which is the titanium quantum dot.
- the manner of drying is not limited, and may be, for example, vacuum drying.
- the first step of low-speed centrifugation is to separate and remove the larger portion of the titanium quantum dots, and the second step of high-speed centrifugation to obtain titanium quantum dots of the desired size.
- the titanium quantum dots produced have a size of less than or equal to 20 nm.
- the titanium quantum dots have a size of 1-10 nm.
- the titanium quantum dots have a size of 10-20 nm.
- the titanium quantum dots have a size of 1-5 nm.
- the titanium quantum dots have a size of 2-3 nm.
- the size of the titanium quantum dots is 1 nm, 2 nm, 3 nm, 4 nm, 5 nm, 6 nm, 7 nm, 8 nm, 9 nm, 10 nm, 11 nm, 12 nm, 13 nm, 14 nm, 15 nm, 16 nm, 17 nm, 18 nm, 19 nm. Or 20nm.
- the number of layers of the titanium quantum dots is not particularly limited.
- the "size" of a titanium quantum dot as used herein refers to the "diameter" of a titanium quantum dot.
- the prior art generally employs a liquid phase lift-off method for stripping a two-dimensional layered material.
- the present invention uses a liquid phase stripping method to peel off a two-dimensional non-layered metal material and has succeeded.
- the method for preparing the nano titanium photothermal preparation further comprises: providing a biocompatible material, mixing the titanium quantum dot with the biocompatible material at 10-30 ° C, and stirring 3 -6h, a nano-titanium photothermal preparation was obtained.
- the titanium quantum dots and the biocompatible material are mixed at 25 ° C for 3-6 h.
- the specific preparation method of the nano titanium photothermal preparation comprises: dissolving the biocompatible material in an appropriate amount of the first solvent to obtain a biocompatible material solution, and dispersing the titanium quantum dots in an appropriate amount.
- a titanium quantum dot dispersion is obtained, and the biocompatible material solution is mixed with the titanium quantum dot dispersion at 10-30 ° C, and stirred for 3-6 hours to obtain a nano titanium photothermal preparation.
- the first solvent is a solvent that can dissolve the biocompatible material, such as when the biocompatible material is polyethylene glycol, the first solvent can be selected as deionized water.
- the second solvent comprises deionized water.
- the agitation rate is from 100 rpm to 700 rpm.
- the obtained mixture is centrifugally dried to obtain a titanium quantum dot coated with a biocompatible material, that is, a nano titanium photothermal preparation is obtained.
- the second aspect of the invention provides a preparation method of a nanometer titanium photothermal preparation based on titanium quantum dots, the preparation method is simple and easy to operate, and the prepared nano titanium photothermal preparation has high light-heat conversion efficiency and good biocompatibility.
- a method for preparing a nanometer titanium photothermal preparation based on titanium quantum dots comprising the following steps:
- the desired metal elemental titanium quantum dots are obtained by centrifugation.
- centrifugal force of 5000 g was used and centrifuged for 35 min. The supernatant was taken, and then the supernatant was centrifuged at 12000 g for 25 min to obtain a precipitate, which was vacuum dried to obtain a titanium quantum dot to obtain a nano-titanium photothermal preparation.
- Figure 1 is an electron micrograph of a metal elemental titanium quantum dot. As shown in Figure 1, the size of the titanium quantum dots is less than 10 nm. Therefore, by observation of the transmission electron microscope, the titanium metal quantum dots can be peeled off by the liquid phase stripping method.
- the absorption spectra of the same concentration of titanium quantum dots are respectively isopropyl alcohol (IPA) and water stripped. It is apparent that the absorption spectrum of the stripped titanium quantum dots in IPA has a higher absorption value and a larger slope (i.e., the upper curve in Fig. 2). This shows that the larger titanium particles can be sufficiently stripped into smaller titanium quantum dots in IPA. Further, the absorption values of different peeling times (referred to as water bath ultrasonic time) were compared (as shown in Fig. 3), and it was found that as the peeling time increased, the absorption spectrum was continuously increased, and a saturated state appeared.
- water bath ultrasonic time the absorption values of different peeling times
- a method for preparing a nanometer titanium photothermal preparation based on titanium quantum dots comprising the following steps:
- the desired metal elemental titanium quantum dots are obtained by centrifugation.
- centrifugal force of 8000 g was used and centrifuged for 20 min. The supernatant was taken, and then the supernatant was centrifuged for 1500 g for 35 min to obtain a precipitate, which was vacuum dried to obtain a titanium quantum dot to obtain a nano-titanium photothermal preparation.
- a method for preparing a nanometer titanium photothermal preparation based on titanium quantum dots comprising the following steps:
- the desired metal elemental titanium quantum dots are obtained by centrifugation.
- centrifugal force of 7000 g was used and centrifuged for 25 min. The supernatant was taken, and then the supernatant was centrifuged at 13,000 g for 20 min to obtain a precipitate, which was dried in a vacuum to obtain a titanium quantum dot to obtain a nano-titanium photothermal preparation.
- a method for preparing a nanometer titanium photothermal preparation based on titanium quantum dots comprising the following steps:
- a method for preparing a nanometer titanium photothermal preparation based on titanium quantum dots comprising the following steps:
- a method for preparing a nanometer titanium photothermal preparation based on titanium quantum dots comprising the following steps:
- aqueous dispersions Different concentrations of aqueous dispersions were prepared to measure absorption spectra and photothermal properties. The absorption spectrum was measured using an ultraviolet-spectrophotometer. For the photothermal experiment, we used a 808 nm laser. 10, 25, 50 and 100 ppm titanium quantum dot aqueous dispersions were prepared separately (as shown in Figure 4). The prepared aqueous dispersion was separately placed in a quartz cuvette and placed in an ultraviolet spectrophotometer card slot to measure the absorbance. The absorption curves of different concentrations are shown in Figure 5. According to the absorption at 808 nm, the extinction coefficient of the titanium quantum dots was 17.6 Lg -1 cm -1 (as shown in Fig. 6).
- the photothermal conversion efficiency (65.4%) of the titanium quantum dots of the present invention is highest among all reported photothermal agents, higher than conventional gold nanoparticles (21%) and emerging two-dimensional photothermal agents: including MoS 2 (24.4) %), black phosphorus quantum dots (28.4%), Ti 3 C 2 nanosheets (30.6%) and germanium quantum dots (45.5%), therefore, the photothermal conversion efficiency of titanium quantum dots is significantly higher than other light currently under study. Thermal agent.
- the titanium quantum dots prepared by the invention have full spectrum absorption and high photothermal conversion efficiency, and the photothermal performance is good.
- the hepatocellular carcinoma cell line SMMC-7721 was first plated into a 96-well plate and prepared for experimentation after the cells were attached (about 12 hours). Titanium quantum dot dispersions at concentrations of 0, 10, 20, 50, 100, 200, and 400 mg/liter were prepared in DMEM high glucose medium, respectively. One hundred microliters of the dispersion was taken, and the medium in the above 96-well plate was replaced. After incubation for 24 hours, the viability of the cells in each well was measured using a CCK8 kit, and three parallel wells were set in each set of experiments. As shown in Figure 9, as the concentration of titanium quantum dots increased (from 0 to 400 mg/L), there was no significant decrease in cell viability compared to the negative control group (Mock) without titanium quantum dots. This indicates that the titanium quantum dots have no obvious cytotoxicity.
- this example also studied the killing ability of the photothermal effect of titanium quantum dots on cancer cells in human liver cancer cell SMMC-7721 cells, and the results are shown in FIG.
- the cells were first plated into 96-well plates and prepared for experimentation after the cells were attached (approximately 12 hours).
- the titanium quantum dots were dispersed into DMEM high sugar complete medium at concentrations of 0, 10, 20, 50, and 100 mg/liter, respectively. 100 ⁇ l of the dispersion was taken, and the medium in the 96-well plate was replaced. After incubation for 2 hours, each well of the 96-well plate was irradiated with an illumination parameter of 808 nm laser at a power of 1 W/cm 2 for 10 minutes.
- the medium containing titanium quantum dots was replaced with fresh complete medium, and after culturing for 24 hours in a cell culture incubator, the viability of the cells in each well was determined by CCK8 kit, and three parallel holes were set in each set of experiments. .
- cells that were not treated at all were used as a negative control group, i.e., the Mock group in the figure. It can be seen from the figure that as the concentration of titanium quantum dots increases, the photothermal effect of the photothermal effect on the cells increases rapidly, and the killing efficiency is close to 100% at 50 mg/L. This shows that the photothermal conversion ability of titanium quantum dots can effectively kill cancer cells, that is, titanium quantum dots can be used for photothermal treatment of cancer.
- This example also examined the in vivo anti-tumor effect of titanium quantum dots in model animals.
- 2 ⁇ 10 6 SMMC-7721 cells were subcutaneously injected into each 6-week-old BALB/c female mouse, and the injection site was the lower side of the left forelimb.
- the human liver cancer mouse model was completed.
- the titanium quantum dots were dispersed in physiological saline to obtain a dispersion of 100 mg/liter for use.
- 100 microliters of physiological saline (control) and 100 microliters of titanium quantum dot dispersion at a concentration of 100 mg/liter were injected intradermally into mouse tumors by subcutaneous injection, followed by titanium quantum dots.
- the group performed photothermal treatment of the tumor.
- the photothermal parameter is 808 nm laser with a power of 1 W/cm 2 and a time of 10 minutes.
- the time of the day of treatment is set to the first day.
- Tumors were measured for tumor length, width, and height on days 1, 3, 5, 7, 9, 11, 13, and 15 of treatment, respectively.
- the tumors in the saline group have been growing rapidly; the experimental group of titanium quantum dots injected and illuminated (shown as titanium quantum dot + photothermal group), the tumor volume is rapidly reduced after treatment. Small and always suppressed. It can be seen that the photothermal effect of titanium quantum dots has potential for photothermal treatment of cancer.
- titanium quantum dots themselves are substantially non-toxic to cancer cells, showing their biocompatibility and safety and non-toxic advantages. And its excellent photothermal effect shows excellent cancer cell killing effect in vitro and in vivo. Thus, titanium quantum dots have clinical potential for photothermal therapy of cancer.
- the polyethylene glycol-coated titanium quantum dots prepared in Examples 4-6 are also subjected to (1) absorption spectrum and photothermal performance test of the above titanium quantum dots; (2) Biological toxicity test (3) Determination of cell killing ability; (4) Determination of tumor photothermal therapy effect.
- the polyethylene glycol-coated titanium quantum dots themselves are substantially non-toxic to cancer cells, and their biocompatibility is similar or superior to that of uncoated titanium quantum dots, indicating their biological phase. Capacitive and safe and non-toxic. And its excellent photothermal effect shows similar or superior cancer cell killing effect to uncoated titanium quantum dots in vitro and in vivo.
- polyethylene glycol-coated titanium quantum dots have clinical potential for photothermal therapy of cancer.
- the nano titanium photothermal preparation prepared by the invention has good photothermal performance and good biocompatibility, and the photothermal effect can be used for cell killing and tumor treatment based on cell killing ability.
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Abstract
一种基于钛量子点的纳米钛光热制剂,包括钛量子点。该纳米钛光热制剂,光热转换效率高、生物相容性好,安全无毒,可用于包括肿瘤在内的光热治疗。一种基于钛量子点的纳米钛光热制剂的制备方法,包括以下步骤:提供钛原料,采用液相剥离法对所述钛原料进行剥离,得到钛量子点,即得基于钛量子点的纳米钛光热制剂。该纳米钛光热制剂的制备方法简单易操作,制得的纳米钛光热制剂光热转换效率高、生物相容性良好。
Description
本发明要求于2018年03月30日递交的申请号为201810299355.3,发明名称为“基于钛量子点的纳米钛光热制剂及其制备方法”的在先申请的优先权,上述在先申请的内容以引入的方式并入本文本中。
本发明涉及生物医用纳米材料领域,具体涉及一种基于钛量子点的纳米钛光热制剂及其制备方法。
目前,对于癌症的治疗,在传统的手术治疗、放射性治疗和化疗之外,又开发出了免疫疗法、细胞疗法等新型疗法。但是,目前的疗法虽然能够在一定程度上延长患者的生命,仍有其局限性,如副作用大、无法完全清除肿瘤细胞、无法治愈等等。因此,开发新的疗法仍然是癌症领域的热点。
基于纳米材料的近红外光疗是一种新型的,有潜力的疗法,特别是近红外光响应的光热治疗,解决了紫外光以及可见光等短波长光疗中光波易被吸收、易散射、具有核酸毒性,以及组织穿透力差的问题。近红外光波长大约在700-1000纳米之间,具有低吸收、高穿透性的优点(1厘米以上)。
目前常规的光热治疗材料主要有金纳米颗粒、碳纳米管以及石墨烯等等。但现有的光热材料往往无法兼顾光热转换效率以及生物相容性。
因此,亟需寻找一种光热转换效率高、生物相容性好、安全无毒的光热材料,用于包括肿瘤在内的光热治疗。
发明内容
为解决上述问题,本发明提供了一种基于钛量子点的纳米钛光热制剂,所述基于钛量子点的纳米钛光热制剂具有光热转换效率较高、生物相容性良好,安全无毒等优点,可用于包括肿瘤在内的光热治疗。
本发明第一方面提供了一种基于钛量子点的纳米钛光热制剂,包括钛量子点。
其中,所述钛量子点的尺寸小于或等于20nm。
其中,所述钛量子点的尺寸为1-10nm。
其中,所述钛量子点的尺寸为10-20nm。
其中,所述钛量子点的尺寸为1-5nm。
其中,所述钛量子点的尺寸为2-3nm。
其中,所述纳米钛光热制剂还包括包覆在所述钛量子点表面的生物相容性材料。
其中,所述生物相容性材料包括透明质酸、葡聚糖及其衍生物、壳聚糖及其衍生物、果胶、羧甲基纤维素、白蛋白、脂质体、细胞膜、聚乙烯吡咯烷酮、聚乳酸-羟基乙酸共聚物、聚乙烯亚胺、聚丙烯酸和聚乙二醇及其衍生物中的一种或多种。
其中,所述聚乙二醇及其衍生物的分子量在200-20000之间。
其中,所述聚乙二醇的末端由氨基修饰。
其中,所述生物相容性材料通过静电作用吸附在所述钛量子点的表面。
其中,所述钛量子点与所述生物相容性材料的质量比为1∶1-10。
其中,所述纳米钛光热制剂还包括靶向材料,所述靶向材料通过化学键连接在所述钛量子点或连接在所述生物相容性材料上。
其中,所述靶向材料为叶酸,所述叶酸通过酰胺键连接在所述聚乙二醇上。
本发明第一方面提供的纳米钛光热制剂,其光热转换效率较高、生物相容性良好,安全无毒,可用于包括肿瘤在内的光热治疗。
本发明第二方面提供了一种基于钛量子点的纳米钛光热制剂的制备方法的制备方法,包括以下步骤:
提供钛原料,采用液相剥离法对所述钛原料进行剥离,得到钛量子点,即得基于钛量子点的纳米钛光热制剂。
其中,所述液相剥离法具体包括以下操作:
将所述钛原料加入至极性溶剂中,在冰浴环境下采用探头超声10-15h;所述探头超声结束后,再采用水浴超声,所述水浴超声时间为6-15h,所述水浴的温度保持5-15℃;所述水浴超声结束后,进行离心和干燥得到钛量子点。
其中,所述极性溶剂包括异丙醇、乙醇、水和N-甲基吡咯烷酮中的至少一种。
其中,所述离心的操作包括:
首先采用5000-8000g的离心力,离心20-35min,取上清液;然后将所述上清液采用10000-13000g的离心力继续离心20-35min,得到沉淀即为所述钛量子点。
其中,所述纳米钛光热制剂的制备方法进一步包括:提供生物相容性材料,将所述钛量子点与所述生物相容性材料在10-30℃下混合后搅拌3-6h,得到纳米钛光热制剂。
其中,所述纳米钛光热制剂的制备方法具体包括:将所述生物相容性材料溶于适量的第一溶剂中后,得到生物相容性材料溶液,将所述钛量子点分散于适量的第二溶剂中,得到钛量子点分散液,将所述生物相容性材料溶液与所述钛量子点分散液在10-30℃下混合后搅拌3-6h,得到纳米钛光热制剂。
本发明第二方面提供了一种基于钛量子点的纳米钛光热制剂的制备方法,制备方法简单易操作,制得的纳米钛光热制剂光热转换效率高、生物相容性良好。
综上,本发明有益效果包括以下几个方面:
1、本发明提供的基于钛量子点的纳米钛光热制剂,光热转换效率较高、生物相容性良好,安全无毒,可用于包括肿瘤在内的光热治疗;
2、本发明提供的纳米钛光热制剂的制备方法,方法简单易操作。
图1为实施例1制得的钛量子点的透射电镜图片;
图2为在不同溶剂中的液相剥离过程的吸收光谱图;
图3为不同超声时间的液相剥离过程的吸收光谱图;
图4为不同浓度的钛量子点水分散液照片;
图5为不同浓度的钛量子点水分散液的吸收光谱图;
图6为钛量子点的消光系数;
图7为不同浓度的钛量子点水分散液的升温曲线;
图8为钛量子点水分散液的光热转换效率;
图9为钛量子点的细胞毒性测定结果图;
图10为钛量子点光热效应对癌细胞的杀伤效果图;
图11为钛量子点的光热效应用于癌症治疗的效果图。
以下所述是本发明的优选实施方式,应当指出,对于本技术领域的普通技术人员来说,在不脱离本发明原理的前提下,还可以做出若干改进和润饰,这些改进和润饰也视为本发明的保护范围。
本发明提到的“钛量子点”或“钛”,除特殊说明,均指的是单质钛。
本发明实施方式第一方面提供了一种基于钛量子点的纳米钛光热制剂,包括钛量子点。
本发明实施方式中,所述钛量子点的尺寸小于或等于20nm。可选地,所述钛量子点的尺寸为1-10nm。可选地,所述钛量子点的尺寸为10-20nm。进一步可选地,所述钛量子点的尺寸为1-5nm。进一步可选地,所述钛量子点的尺寸为2-3nm。进一步可选地,所述钛量子点的尺寸为1nm、2nm、3nm、4nm、5nm、6nm、7nm、8nm、9nm、10nm、11nm、12nm、13nm、14nm、15nm、16nm、17nm、18nm、19nm或20nm。可选地,对所述钛量子点的层数不做特殊限制。这里所说的钛量子点的“尺寸”指的也是钛量子点的“直径”。
本发明实施方式提供的所述钛量子点尺寸较小,较小的尺寸有助于钛量子点在肿瘤部位具有较好的被动富集效果,且容易从体内排出,生物相容性良好。同时,所述钛量子点的光热效果明显。
本发明实施方式中,所述钛量子点具有从可见光区到近红外光区的吸收。可选地,所述钛量子点的光吸收波长范围为200-2000nm。
本发明实施方式中,所述钛量子点的光热转换效率为大于或等于60%。
本发明提供的钛量子点具有环境友好、生物兼容性、全光谱的强吸收和较高的光热转换效率等优点,具有优良的光热性能。
本发明实施方式中,所述生物相容性材料包括透明质酸、葡聚糖及其衍生物、壳聚糖及其衍生物、果胶、羧甲基纤维素、白蛋白、脂质体、细胞膜、聚乙烯吡咯烷酮、聚乳酸-羟基乙酸共聚物、聚乙烯亚胺、聚丙烯酸和聚乙二醇及其衍生物中的一种或多种。进一步可选地,所述生物相容性材料包括聚乙二醇及其衍生物、聚乳酸-羟基乙酸共聚物、白蛋白、脂质体和细胞膜中的至少一种。进一步可选地,所述生物相容性材料包括聚乙二醇及其衍生物,所述聚乙二醇及其衍生物的分子量在200-20000之间。可选地,所述聚乙二醇的末端可以由氨基修饰。可选地,所述生物相容性材料通过静电作用吸附在所述钛量子点的表面。
本发明实施方式中,所述纳米钛光热制剂还包括靶向材料,所述靶向材料通过化学键连接在所述钛量子点或连接在所述生物相容性材料上。可选地,所述靶向材料为叶酸,所述叶酸通过酰胺键连接在所述聚乙二醇上。
本发明实施方式中,所述纳米钛光热制剂可以分散在生理盐水、磷酸盐缓冲液或去离子水中用于后续应用。
本发明实施方式中,所述钛量子点和所述生物相容性材料的质量比为1∶1-10。可选地,所述钛量子点和所述生物相容性材料的质量比为1∶1、1∶2、1∶3、1∶4、1∶5、1∶6、1∶7、1∶8、1∶9或1∶10。
本发明第一方面提供的纳米钛光热制剂,光热转换效率高、生物相容性好,安全无毒,可用于包括肿瘤在内的光热治疗。
本发明实施例第二方面提供了一种基于钛量子点的纳米钛光热制剂的制备方法,包括以下步骤:
提供钛原料,采用液相剥离法对所述钛原料进行剥离,得到钛量子点,即得基于钛量子点的纳米钛光热制剂。
本发明实施方式中,所述钛原料为二维非层状的金属钛单质,如可以为钛粉,如粒径为微米级的钛粉,具体可以为粒径为几十微米左右或以下的钛粉。也可以为钛块,对其大小和形状没有特殊限定。如果钛原料为粒径较大的钛块,可以先对钛块进行研磨,研磨后用于液相剥离。所述钛原料可通过购买得到。
本发明实施方式中,所述液相剥离法具体包括以下操作:
将所述钛原料加入至极性溶剂中,在冰浴环境下采用探头超声10-15h;所述探头超声结束后,再采用水浴超声,所述水浴超声时间为6-15h,所述水浴的温度保持5-15℃;所述水浴超声结束后,进行离心和干燥得到钛量子点。
可选地,所述极性溶剂包括异丙醇、乙醇、水和N-甲基吡咯烷酮(NMP)中的至少一种。可选地,所述极性溶剂包括异丙醇、乙醇和N-甲基吡咯烷酮(NMP)中的至少一种。本发明采用的溶剂可以对钛原料进行剥离,制得钛量子点。
可选地,所述钛原料在所述溶剂中的浓度为1-7mg/mL。
可选地,所述探头超声的功率为250-300W。进一步可选地,所述探头超声的功率为250W、260W、270W、280W、290W或300W。
可选地,所述探头超声的时间为10h、11h、12h、13h、14h或15h。
可选地,所述探头超声是非连续超声,选择超声开/关时间为2/4s,即先超声2s,然后关闭超声探头保持4s,在继续超声2s,以此类推。
可选地,所述水浴超声功率为350-400W。进一步可选地,所述水浴超声功率为350W、360W、370W、380W、390W或400W。
可选地,所述水浴超声的时间为10-15h。具体地,所述水浴超声的时间为6h、7h、8h、9h、10h、11h、12h、13h、14h或15h。
可选地,所述水浴温度保持10℃。
可选地,超声后,进行离心,所述离心的操作包括:首先采用5000-8000g的离心力,离心20-35min,取上清液;然后将所述上清液采用10000-13000g的离心力继续离心20-35min,得到沉淀即为所述钛量子点。可选地,所述干燥的方式不限,例如可为真空干燥。第一步的低转速离心是为了分离去除尺寸较大的那部分钛量子点,第二步的高速离心分离即获得所需尺寸的钛量子点。
本发明实施方式中,制得的所述钛量子点的尺寸小于或等于20nm。可选地,所述钛量子点的尺寸为1-10nm。可选地,所述钛量子点的尺寸为10-20nm。进一步可选地,所述钛量子点的尺寸为1-5nm。进一步可选地,所述钛量子点的尺寸为2-3nm。进一步可选地,所述钛量子点的尺寸为1nm、2nm、3nm、4nm、5nm、6nm、7nm、8nm、9nm、10nm、11nm、12nm、13nm、14nm、15nm、16nm、17nm、18nm、19nm或20nm。可选地,对所述钛量子点的层数不做特殊限制。这里所说的钛量子点的“尺寸”指的也是钛量子点的“直径”。
现有技术通常采用液相剥离法用来剥离二维层状材料。而本发明采用液相剥离法剥离二维非层状金属材料,并取得成功。
本发明实施方式中,所述纳米钛光热制剂的制备方法进一步包括:提供生物相容性材料,将所述钛量子点与所述生物相容性材料在10-30℃下混合后搅拌3-6h,得到纳米钛光热制剂。
可选地,将钛量子点和生物相容性材料在25℃下混合3-6h。
本发明实施方式中,所述纳米钛光热制剂的具体制备方法包括:将生物相容性材料溶于适量的第一溶剂中后,得到生物相容性材料溶液,将钛量子点分散于适量的第二溶剂中,得到钛量子点分散液,将所述生物相容性材料溶液与所述钛量子点分散液在10-30℃下混合后搅拌3-6h,得到纳米钛光热制剂。
可选地,所述第一溶剂为可以溶解生物相容性材料的溶剂,如当生物相容性材料为聚乙二醇时,第一溶剂可以选择去离子水。
可选地,所述第二溶剂包括去离子水。
本发明实施方式中,所述搅拌速率为100转/min-700转/min。
本发明实施方式中,搅拌后,将所得混合物离心干燥后,得到生物相容性材料包覆的钛量子点,即得纳米钛光热制剂。
本发明第二方面提供了一种基于钛量子点的纳米钛光热制剂的制备方法,制备方法简单易操作,制得的纳米钛光热制剂光热转换效率较高、生物相容性良好。
实施例1:
一种基于钛量子点的纳米钛光热制剂的制备方法,包括以下步骤:
(1)将500mg的钛粉加入100mL的异丙醇中。然后选择探头超声250W,超声15h。选择超声开/关时间为2/4s,并且是在冰浴环境下进行超声。探头超声完后,接着采用水浴超声。水浴超声功率为360W。超声时间为12h。水浴温度保持10℃;
(2)超声过后采用离心的办法得到需要的金属单质钛量子点。首先采用5000g的离心力,离心35min。取上清,然后将上清采用12000g继续离心25min, 得到沉淀,真空干燥后得到钛量子点即得纳米钛光热制剂。
图1为金属单质钛量子点的电镜形貌图。如图1所示,钛量子点的尺寸小于10nm。因此通过透射电镜的观察,通过液相剥离法确实可以剥离出金属钛量子点。
如图2所示,分别为异丙醇(IPA)和水中剥离的,相同浓度的钛量子点的吸收光谱。很明显,IPA中剥离的钛量子点的吸收光谱具有更高的吸收值和更大的斜率(即图2中上面的一条曲线)。这说明IPA中可以充分将比较大的钛颗粒剥离成较小的钛量子点。进一步,比较了不同剥离时间(指的是水浴超声时间)的吸收值(如图3所示),发现随着剥离时间的增加,吸收光谱在不断增加,而且会出现一个饱和的状态。
实施例2:
一种基于钛量子点的纳米钛光热制剂的制备方法,包括以下步骤:
(1)将500mg的钛粉加入100mL的N-甲基吡咯烷酮中。然后选择探头超声300W,超声10h。选择超声开/关时间为2/4s,并且是在冰浴环境下进行超声。探头超声完后,接着采用水浴超声。水浴超声功率为350W。超声时间为15h。水浴温度保持15℃;
(2)超声过后采用离心的办法得到需要的金属单质钛量子点。首先采用8000g的离心力,离心20min。取上清,然后将上清采用10000g继续离心35min,得到沉淀,真空干燥后得到钛量子点即得纳米钛光热制剂。
实施例3:
一种基于钛量子点的纳米钛光热制剂的制备方法,包括以下步骤:
(1)将500mg的钛粉加入100mL的乙醇中。然后选择探头超声280W,超 声12h。选择超声开/关时间为2/4s,并且是在冰浴环境下进行超声。探头超声完后,接着采用水浴超声。水浴超声功率为400W。超声时间为6h。水浴温度保持5℃;
(2)超声过后采用离心的办法得到需要的金属单质钛量子点。首先采用7000g的离心力,离心25min。取上清,然后将上清采用13000g继续离心20min,得到沉淀,真空干燥后得到钛量子点即得纳米钛光热制剂。
实施例4
一种基于钛量子点的纳米钛光热制剂的制备方法,包括以下步骤:
提供PEG2000水溶液,将实施例1制得的钛量子点分散在适量水中得到钛量子点分散液,将钛量子点分散液与PEG2000溶液混合,其中,钛量子点与PEG2000的质量比为1∶1,在25℃下混合搅拌5h,离心干燥后,得到PEG2000包覆的钛量子点即得基于钛量子点的纳米钛光热制剂。
实施例5
一种基于钛量子点的纳米钛光热制剂的制备方法,包括以下步骤:
提供PEG2000溶液,将实施例2制得钛量子点分散在适量水中得到钛量子点分散液,将钛量子点分散液与PEG2000溶液混合,其中,钛量子点与PEG2000的质量比为1∶10,在30℃下混合搅拌3h,离心干燥后,得到PEG2000包覆的钛量子点即得基于钛量子点的纳米钛光热制剂。
实施例6
一种基于钛量子点的纳米钛光热制剂的制备方法,包括以下步骤:
提供PEG2000溶液,将实施例3制得的钛量子点分散在适量水中得到钛量子点分散液,将钛量子点分散液与PEG2000溶液混合,其中,钛量子点与 PEG2000的质量比为1∶5,在10℃下混合搅拌6h,离心干燥后,得到PEG2000包覆的钛量子点即得基于钛量子点的纳米钛光热制剂。
效果实施例
(1)吸收光谱和光热性能的测试
配制不同浓度的水分散液测量吸收光谱和光热性能。吸收光谱采用紫外-分光光度计测量。光热实验我们采用808nm激光。分别配制10,25,50和100ppm的钛量子点水分散液(如图4所示)。将配制的水分散液分别装入石英比色皿中,放入紫外分光光度计卡槽中测量吸收度。不同浓度的吸收曲线如图5所示。根据808nm处的吸收可以得到钛量子点的消光系数为17.6Lg
-1cm
-1(如图6所示)。该值高于黑磷(14.8Lg
-1cm
-1)的消光系数。对于光热实验的测量,取1mL不同浓度的钛量子点水分散液加入比色皿中,采用808nm激光进行照射,并同时用热电偶记录温度曲线。图7显示的是不同浓度的钛量子点的温度随激光照射时间的升温图。通过定量的计算,可以得到钛量子点的光热转换效率为65.4%(如图8所示)。
本发明的钛量子点的光热转换效率(65.4%)在所有报道的光热剂中最高,高于传统的金纳米颗粒(21%)以及新兴的二维光热剂:包括MoS
2(24.4%)、黑磷量子点(28.4%)、Ti
3C
2纳米片(30.6%)和锑量子点(45.5%),因此,钛量子点光热转换效率值明显高于其他当前正在研究的光热剂。
因此,本发明制得的钛量子点具有全光谱的吸收和较高的光热转换效率,光热性能良好。
(2)钛量子点的生物毒性测试
将不同质量的钛量子点分散于细胞培养基,再与不同的细胞共孵育,再测定细胞的活力。首先将肝细胞癌细胞SMMC-7721铺到96孔板中,待细胞贴壁(大约12小时)后,准备用于实验。以DMEM高糖培养基分别配制浓度为0、10、20、50、100、200以及400毫克/升的钛量子点分散液。取100微升分散液,置换前述96孔板中的培养基,在孵育24小时之后,使用CCK8试剂盒测定每个孔里面细胞的活力,每一组实验设置3个平行孔。如图9所示,随着钛量子点浓度的提高(从0到400毫克/升),和未加钛量子点的阴性对照组(Mock)对比,其细胞活力并无明显的下降。这说明钛量子点没有明显的细胞毒性。
(3)基于钛量子点光热效应的细胞杀伤能力测定
随后,本实施例也在人肝癌细胞SMMC-7721细胞中研究了钛量子点的光热效应对癌细胞的杀伤能力,结果如图10所示。首先将细胞铺到96孔板中,待细胞贴壁(大约12小时)后,准备用于实验。将钛量子点分散到DMEM高糖完全培养基中,浓度分别为0、10、20、50、100毫克/升。取100微升分散液,置换前述96孔板中的培养基,在孵育2小时后,对96孔板各个孔进行光照,光照参数为808nm激光,功率为1W/cm
2,时间为10分钟。光热后用新鲜的完全培养基置换含有钛量子点的培养基,在细胞培养箱中培养24小时后,用CCK8试剂盒测定每个孔里面细胞的活力,每一组实验设置3个平行孔。如图10所示,以完全不处理的细胞作为阴性对照组,即图中的Mock组。从图中可以看出,随着钛量子点浓度的升高,其光热效应对细胞的杀伤能力迅速升高,在50毫克/升时杀伤效率接近100%。这说明利用钛量子点的光热转换能力,能够高效地杀伤癌细胞,即钛量子点可用于癌症的光热治疗。
(4)基于钛量子点光热效应的肿瘤光热治疗效果测定
本实施例也在模式动物中检测了钛量子点的体内抗肿瘤效应。首先在每只6周龄的BALB/c雌性小鼠中皮下注射2×10
6个SMMC-7721细胞,注射部位为左前肢下方侧面。用游标卡尺测定肿瘤的体积(体积=长度×宽度×高度÷2),待体积达到100-200立方毫米时,可用于治疗实验。此时,人肝癌小鼠模型构建完毕。
将钛量子点分散于生理盐水,得到100毫克/升的分散液备用。通过皮下注射的方式将100微升的生理盐水(对照)、100微升的浓度为100毫克/升的钛量子点分散液通过瘤内注射的方式注射到小鼠肿瘤中,随后对钛量子点组进行肿瘤的光热治疗。光热参数为808纳米激光,功率为1W/cm
2,时间为10分钟。治疗的当天的时间设置为第一天。
分别在治疗的第1,3,5,7,9,11,13,15天测定肿瘤的长、宽和高,计算肿瘤体积。如图11所示,生理盐水组小鼠所荷肿瘤一直在快速增长;而钛量子点注射并进行光照的实验组(图中显示为钛量子点+光热组),治疗后肿瘤体积迅速减小,并且一直被抑制。由此可知,钛量子点的光热效应有用于癌症光热治疗的潜力。
综上所述,钛量子点自身对癌细胞基本没有毒性,显示了其生物相容性以及安全无毒的优点。而其优异的光热效应,在体外、体内都显示了优异的癌细胞杀伤效应。由此,钛量子点有用于癌症光热治疗的临床潜力。
本发明实施例还将实施例4-6制备的聚乙二醇包覆的钛量子点也进行了例如上述钛量子点的(1)吸收光谱和光热性能的测试;(2)生物毒性测试;(3)细胞杀伤能力测定;(4)肿瘤光热治疗效果测定。根据测试结果可知,聚乙二醇包覆的钛量子点自身对癌细胞基本没有毒性,其生物相容性与未包覆的钛 量子点相比,效果相似或更优异,显示了其生物相容性以及安全无毒的优点。而其优异的光热效应,在体外、体内都显示了与未包覆的钛量子点相似或更优异的癌细胞杀伤效应。由此,聚乙二醇包覆的钛量子点有用于癌症光热治疗的临床潜力。
综上,本发明制得的纳米钛光热制剂具有良好的光热性能,兼具良好的生物相容性,其光热效应可以用于细胞杀伤以及基于细胞杀伤能力的肿瘤治疗。
以上所述实施例仅表达了本发明的几种实施方式,其描述较为具体和详细,但并不能因此而理解为对本发明专利范围的限制。应当指出的是,对于本领域的普通技术人员来说,在不脱离本发明构思的前提下,还可以做出若干变形和改进,这些都属于本发明的保护范围。因此,本发明专利的保护范围应以所附权利要求为准。
Claims (20)
- 一种基于钛量子点的纳米钛光热制剂,其中,包括钛量子点。
- 如权利要求1所述的纳米钛光热制剂,其中,所述钛量子点的尺寸小于或等于20nm。
- 如权利要求1所述的纳米钛光热制剂,其中,所述钛量子点的尺寸为1-10nm。
- 如权利要求1所述的纳米钛光热制剂,其中,所述钛量子点的尺寸为10-20nm。
- 如权利要求1所述的纳米钛光热制剂,其中,所述钛量子点的尺寸为1-5nm。
- 如权利要求1所述的纳米钛光热制剂,其中,所述钛量子点的尺寸为2-3nm。
- 如权利要求1所述的纳米钛光热制剂,其中,所述纳米钛光热制剂还包括包覆在所述钛量子点表面的生物相容性材料。
- 如权利要求7所述的纳米钛光热制剂,其中,所述生物相容性材料包括透明质酸、葡聚糖及其衍生物、壳聚糖及其衍生物、果胶、羧甲基纤维素、白蛋白、脂质体、细胞膜、聚乙烯吡咯烷酮、聚乳酸-羟基乙酸共聚物、聚乙烯亚胺、聚丙烯酸和聚乙二醇及其衍生物中的一种或多种。
- 如权利要求8所述的纳米钛光热制剂,其中,所述聚乙二醇及其衍生物的分子量在200-20000之间。
- 如权利要求8所述的纳米钛光热制剂,其中,所述聚乙二醇的末端由 氨基修饰。
- 如权利要求7所述的纳米钛光热制剂,其中,所述生物相容性材料通过静电作用吸附在所述钛量子点的表面。
- 如权利要求7所述的纳米钛光热制剂,其中,所述钛量子点与所述生物相容性材料的质量比为1∶1-10。
- 如权利要求8所述的纳米钛光热制剂,其中,所述纳米钛光热制剂还包括靶向材料,所述靶向材料通过化学键连接在所述钛量子点或连接在所述生物相容性材料上。
- 如权利要求13所述的纳米钛光热制剂,其中,所述靶向材料为叶酸,所述叶酸通过酰胺键连接在所述聚乙二醇上。
- 一种基于钛量子点的纳米钛光热制剂的制备方法,其中,包括以下步骤:提供钛原料,采用液相剥离法对所述钛原料进行剥离,得到钛量子点,即得基于钛量子点的纳米钛光热制剂。
- 如权利要求15所述的纳米钛光热制剂的制备方法,其中,所述液相剥离法具体包括以下操作:将所述钛原料加入至极性溶剂中,在冰浴环境下采用探头超声10-15h;所述探头超声结束后,再采用水浴超声,所述水浴超声时间为6-15h,所述水浴的温度保持5-15℃;所述水浴超声结束后,进行离心和干燥得到所述钛量子点。
- 如权利要求16所述的纳米钛光热制剂的制备方法,其中,所述极性溶剂包括异丙醇、乙醇、水和N-甲基吡咯烷酮中的至少一种。
- 如权利要求16所述的纳米钛光热制剂的制备方法,其中,所述离心的 操作包括:首先采用5000-8000g的离心力,离心20-35min,取上清液;然后将所述上清液采用10000-13000g的离心力继续离心20-35min,得到沉淀即为所述钛量子点。
- 如权利要求16所述的纳米钛光热制剂的制备方法,其中,所述纳米钛光热制剂的制备方法进一步包括:提供生物相容性材料,将所述钛量子点与所述生物相容性材料在10-30℃下混合后搅拌3-6h,得到纳米钛光热制剂。
- 如权利要求19所述的纳米钛光热制剂的制备方法,其中,所述纳米钛光热制剂的制备方法具体包括:将所述生物相容性材料溶于适量的第一溶剂中后,得到生物相容性材料溶液,将所述钛量子点分散于适量的第二溶剂中,得到钛量子点分散液,将所述生物相容性材料溶液与所述钛量子点分散液在10-30℃下混合后搅拌3-6h,得到纳米钛光热制剂。
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