CN112641946A - Polydopamine-coated gold nano-composite, preparation method thereof and application thereof in multi-modal tumor diagnosis and treatment - Google Patents

Polydopamine-coated gold nano-composite, preparation method thereof and application thereof in multi-modal tumor diagnosis and treatment Download PDF

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CN112641946A
CN112641946A CN202110070188.7A CN202110070188A CN112641946A CN 112641946 A CN112641946 A CN 112641946A CN 202110070188 A CN202110070188 A CN 202110070188A CN 112641946 A CN112641946 A CN 112641946A
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gold nano
gold
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acid solution
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许经伟
程侠菊
周秀霞
郁喆
彭勇
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Suzhou Municipal Hospital
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    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K41/00Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
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    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61K31/704Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin
    • AHUMAN NECESSITIES
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    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/34Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K49/00Preparations for testing in vivo
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K49/00Preparations for testing in vivo
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents

Abstract

The invention discloses a gold nano-composite wrapped by polydopamine, a preparation method thereof and application thereof in multi-mode tumor diagnosis and treatment. Mixing a chloroauric acid solution and a hexadecyltrimethylammonium chloride solution at room temperature, and then adding a precooled sodium borohydride solution for reaction to prepare a gold nano-seed solution; adding the gold nano seed solution into a mixed solution consisting of a chloroauric acid solution, a hexadecyltrimethylammonium chloride solution, a hydrochloric acid solution, a silver nitrate solution and an ascorbic acid solution, standing, and then carrying out ultrafiltration centrifugation, washing and water adding for heavy suspension to prepare a gold nano bone solution; and mixing the gold nano bone solution with a dopamine hydrochloride solution, and carrying out ultrasonic treatment to obtain the gold nano composite coated with polydopamine. The invention realizes the purpose of tumor photothermal and chemical combined synergistic treatment by utilizing the strong photothermal conversion performance and the high-carrying-capacity chemotherapeutic drug performance of the polydopamine-coated gold nano bone composite material.

Description

Polydopamine-coated gold nano-composite, preparation method thereof and application thereof in multi-modal tumor diagnosis and treatment
Technical Field
The invention belongs to a tumor diagnosis and treatment technology, and particularly discloses a polydopamine-coated gold nano-composite, a preparation method thereof and application thereof in tumor multi-mode diagnosis and treatment.
Background
With the rapid development of nanoscience, more and more multifunctional diagnostic and therapeutic nanomaterials are used for efficient and safe antitumor therapy. Particularly real-time imaging guided photothermal therapy, is receiving increasing attention because of its non-invasiveness and safety. While photothermal therapy alone is effective in inhibiting tumor growth, complete elimination of the tumor is difficult due to scattering of light in biological tissues. Therefore, scientists are interested in bimodal combination therapy based on photothermal therapy, and multimodal synergistic therapy based on photothermal therapy, in which the heat generated by photothermal therapy accelerates intracellular delivery and release of drugs, immunotherapeutic antibodies or photosensitizers, accelerates blood flow in tumors to improve the oxygenation process of tumors, and has an enhancing effect on chemotherapy, immunotherapy, photodynamic therapy and radiotherapy, in addition to the treatment of tumors by thermal ablation.
The gold nano material has unique physical and chemical properties such as light, electricity, heat, catalysis and the like, is an important component for constructing a novel composite functional material, and has wide application prospect in the fields of biosensing, cell and living body imaging, photo-thermal treatment of cancer cells, targeted drug loading, photochemical catalysis and the like. Recently, various gold-based multifunctional nanocomposites have attracted attention and are designed for tumor therapy. The gold nano-material composites not only have the functions of all components, but also have synergistic effect. The application basic research of the material such as the gold nano-composite coated by the polydopamine is more.
The currently published studies of polydopamine-encapsulated gold nanocomposites can be roughly classified into the following types: (1) gold nanoparticles are wrapped by polydopamine, and Au @ PDA @ BD nanoparticles which can be used for CT imaging guided photo-thermal treatment are reported by Li and the like; sun et al reported Au @ PDA-I for SPECT/CT imaging-guided radiosensitization therapy125Nanoparticles. (2) Gold nanorods coated with polydopamine, Liu et al reported that AuNR @ cupad was used in photothermal-chemical combination therapy. Khlebtsov et al report AuNRs-PDA-R with targeting properties for fluorescence imaging guided photothermal therapy123-a folate complex material. Wang et al reported AuNR @ PDA-MB/DOX composite materials useful in photothermal therapy in combination with photodynamic or chemotherapeutic treatments. (3) Polydopamine wraps other gold nano materials in different shapes, such as polydopamine wrapped gold nano star AuNS-DOX @ PDA used for tumor photothermal-chemotherapy, polydopamine wrapped branch-shaped gold-silver nano material Au-Ag @ PDA used for tumor photothermal therapy, polydopamine wrapped gold nano flower PDA-Ce6-GSH-AuNFs used for tumor photothermal-photodynamic combined therapy and the like. In conclusion, the gold nano composite material coated by polydopamine is a highly competitive candidate material in the field of multi-mode tumor diagnosis and treatment integration, and indicates that the application prospect of the gold nano composite material in the field of biomedicine is wider. In addition, the morphology of the nanoparticles and the structural relationship between the gold nanoparticles and dopamine influence the performance of the nanoparticles, so that a new gold nanoparticle-coated polydopamine material needs to be developed to obtain better dimensional stability and photothermal performance.
Disclosure of Invention
The invention discloses a novel polydopamine-coated gold nano-bone (AuNBs @ PDA) composite material and a synthesis preparation method thereof, and the purpose of tumor photothermal and chemical combined synergistic treatment is realized by utilizing the strong light-heat conversion performance and the high-carrying-band chemotherapeutic drug performance of the polydopamine-coated gold nano-bone composite material.
The invention adopts the following technical scheme:
the preparation method of the gold nano-composite coated with polydopamine comprises the steps of mixing a chloroauric acid solution and a hexadecyltrimethylammonium chloride solution at room temperature, and then adding a sodium borohydride solution for reaction to prepare a gold nano-seed solution; adding the gold nano seed solution into a mixed solution consisting of a chloroauric acid solution, a hexadecyltrimethylammonium chloride solution, a hydrochloric acid solution, a silver nitrate solution and an ascorbic acid solution, standing, and then carrying out ultrafiltration centrifugation, washing and water adding for heavy suspension to prepare a gold nano bone solution; and mixing the gold nano bone solution with a dopamine hydrochloride solution, and carrying out ultrasonic treatment to obtain the gold nano composite coated with polydopamine.
The invention discloses a nano-drug which is prepared by loading a small-molecule drug on a gold nano-composite coated with polydopamine; the preparation method of the polydopamine-coated gold nano-composite comprises the steps of mixing a chloroauric acid solution and a hexadecyltrimethylammonium chloride solution at room temperature, and then adding a sodium borohydride solution for reaction to prepare a gold nano-seed solution; adding the gold nano seed solution into a mixed solution consisting of a chloroauric acid solution, a hexadecyltrimethylammonium chloride solution, a hydrochloric acid solution, a silver nitrate solution and an ascorbic acid solution, standing, and then carrying out ultrafiltration centrifugation, washing and water adding for heavy suspension to prepare a gold nano bone solution; and mixing the gold nano bone solution with a dopamine hydrochloride solution, and carrying out ultrasonic treatment to obtain the gold nano composite coated with polydopamine.
In the invention, when preparing the gold nano-seed solution, the concentration of the chloroauric acid solution is 10mM, the concentration of the cetyltrimethylammonium chloride solution is 0.1M, and the concentration of the sodium borohydride solution is 10 mM; the volume ratio of the chloroauric acid solution to the hexadecyl trimethyl ammonium chloride solution to the sodium borohydride solution is (0.4-0.6) to 10 to (0.5-0.7), and preferably, the volume ratio of the chloroauric acid solution to the hexadecyl trimethyl ammonium chloride solution to the sodium borohydride solution is 0.5 to 10 to 0.6; the reaction time is 1-3 hours, preferably 2 hours.
In the invention, when preparing the mother liquor of the gold nano-bone, the concentration of a chloroauric acid solution is 10mM, the concentration of a hexadecyltrimethylammonium chloride solution is 0.1M, the concentration of a hydrochloric acid solution is 1mM, the concentration of a silver nitrate solution is 3mM, and the concentration of an ascorbic acid solution is 100 mM; the volume ratio of the hexadecyl trimethyl ammonium chloride solution to the silver nitrate solution to the hydrochloric acid solution to the chloroauric acid solution to the ascorbic acid solution to the gold nano-seed solution is 10: 0.08-0.12: 0.15-0.25: 0.4-0.6: 0.05-0.15: 0.009-0.011, and preferably, the volume ratio of the hexadecyl trimethyl ammonium chloride solution to the silver nitrate solution to the hydrochloric acid solution to the chloroauric acid solution to the ascorbic acid solution to the gold nano-seed solution is 10: 0.1: 0.2: 0.5: 0.1: 0.01; preferably, mixing a hexadecyl trimethyl ammonium chloride solution, a silver nitrate solution, a hydrochloric acid solution and a chloroauric acid solution, standing for 10-20 minutes, and then adding an ascorbic acid solution and a gold nano-seed solution; and then standing for 10-15 hours, and then carrying out conventional ultrafiltration centrifugation, washing with a buffer solution, adding water and carrying out heavy suspension to prepare the gold nano-bone mother liquor.
According to the invention, the dosage ratio of the gold nano-bone to the dopamine hydrochloride solution is 1 mg: 0.8-1.2 ml; the concentration of the dopamine hydrochloride solution is 2 mM. Further, mixing the gold nano bone solution with a dopamine hydrochloride solution, adjusting the pH value to 8.5, and carrying out ultrasonic treatment for 15-25 min to obtain the polydopamine-coated gold nano composite.
The invention discloses application of the polydopamine-coated gold nano-composite in loading of small-molecule drugs, or in preparation of small-molecule drug carriers, or in preparation of nano-drugs.
In the invention, the small molecule drug is a small molecule antitumor drug, such as adriamycin (DOX).
In the invention, the small molecular drug is added into the polydopamine-coated gold nano-composite solution and stirred in the dark to obtain the nano-drug.
The invention further discloses application of the polydopamine-coated gold nano-composite in preparation of a photo-thermal reagent; or the application of the polydopamine-coated gold nano-composite in the preparation of a CT imaging reagent, or the application of the polydopamine-coated gold nano-composite in the preparation of a photoacoustic imaging reagent, or the application of the polydopamine-coated gold nano-composite in the preparation of a tumor treatment drug, or the application of the nano-drug in the preparation of a tumor treatment drug. Preferably, the tumor treatment medicine is a chemotherapy and photothermal combined tumor treatment medicine.
Specifically, the polydopamine-coated gold nanocomposite is prepared as follows:
gold nanobody (AuNBs) synthesis: preparing gold nano-bone by using a seed crystal growth method, mixing chloroauric acid and cetyltrimethylammonium chloride (CTAC) at room temperature, and then adding sodium borohydride for reaction to obtain a brown gold nano-seed solution; adding gold nano seeds into a mixed solution of a chloroauric acid solution, a CTAC solution, a silver nitrate solution and an ascorbic acid solution, standing overnight, and then carrying out ultrafiltration centrifugation, buffer solution washing and water adding resuspension to obtain a gold nano bone mother solution;
synthesis of poly-dopamine-coated gold nano-composite (AuNBs @ PDA composite): mixing the gold nano-bone mother liquor with dopamine hydrochloride solution at room temperature, carrying out ultrasonic treatment under the condition of keeping out of the sun for 3 times, then carrying out ultrafiltration and centrifugation to obtain a poly-dopamine-coated gold nano composite, and storing the poly-dopamine-coated gold nano composite in the form of AuNBs @ PDA composite solution.
Loading of AuNBs @ PDA composite to Doxorubicin (DOX): adding the DOX solution into the AuNBs @ PDA composite material solution, and stirring in a dark place at 25 ℃ to obtain an adriamycin-loaded polydopamine-coated gold nano composite which is a nano medicament; and finally, centrifugally detecting the absorption value of the supernatant, and calculating the amount of redundant DOX, thereby obtaining the loading amount and the loading efficiency of the DOX in the composite material structure.
Due to the application of the technical scheme, compared with the prior art, the novel synthesis preparation method of the AuNBs @ PDA composite material has the following advantages:
(1) according to the invention, the bone morphology gold nano-material with uniform size is prepared, and the surface of the bone morphology gold nano-material is coated with a layer of polydopamine, so that the photo-thermal conversion efficiency of the bone morphology gold nano-material can be greatly improved, and the bone morphology gold nano-material can be highly loaded with DOX drugs;
(2) the AuNBs @ PDA composite material with the novel high-load chemical drug DOX is utilized to release the drug performance at low pH and temperature responsiveness, and the purpose of combined and synergistic treatment of tumor photothermal/chemotherapy is realized at the cellular and animal level.
Drawings
FIG. 1 is a basic property characterization of AuNBs @ PDA nanocomposites prepared in example 1;
FIG. 2 is a representation of photothermal properties of AuNBs @ PDA nanocomposites;
FIG. 3 is a representation of AuNBs @ PDA composite load DOX;
FIG. 4 shows the result of imaging AuNBs @ PDA composite;
FIG. 5 shows the results of combined photothermal and chemical treatments of AuNBs @ PDA/DOX composite tumor.
Detailed Description
Based on the influence of the morphology of the nano particles on the technical effect, researchers develop a new method to obtain the nano particles with different structural morphologies so as to obtain a more appropriate technical effect. The preparation method is the key of the formation of the morphology of the nano particles, and the rod-shaped gold nano particles are obtained by using the growth of a gold nano seed solution in the prior art, which is not reported in the report of bone-shaped gold nano particles. The preparation method is limited to obtain the bone-shaped gold nanoparticles, the lengthwise length of the bone-shaped gold nanoparticles is 44.2 +/-1.4 nm, the transverse diameter of the bone-shaped gold nanoparticles is 18.7 +/-1.4 nm, and the diameters of two ends of the bone-shaped gold nanoparticles are larger than the diameter of the middle of the bone-shaped gold nanoparticles.
The raw materials involved in the invention are all commercial products or products prepared conventionally in the field, and the specific preparation operation method and the test method are conventional in the field, such as CN 104209533A. The invention is further illustrated by combining specific examples, the creativity of the invention is not in the preparation of raw materials, but in the reaction of the existing raw materials under the conditions of limited proportion and limited process parameters, the novel gold nanoparticles are obtained, dopamine is further wrapped, and the application performance is excellent. It should be understood that these examples are for illustrative purposes only and are not intended to limit the scope of the present invention. Further, it should be understood that various changes or modifications of the present invention may be made by those skilled in the art after reading the teaching of the present invention, and such equivalents may fall within the scope of the present invention as defined in the appended claims.
Example 1 AuNBs @ PDA composite Synthesis
CTAC solution (0.1M, 10 mL) and HAuCl were combined at room temperature4The solutions (10 mM, 250. mu.L) were mixed, stirred routinely for 5min, then NaBH was added4Solution (0.6 mL, 10 mM), solutionChanging the color from yellow to brown, and reserving the gold nano seed solution for later use; next, a CTAC solution (0.1M, 10 mL), AgNO3Solution (3 mM, 100. mu.L), HCl solution (1M, 200. mu.L) and HAuCl4Adding the solution (10 mM, 0.5 mL) into a 50 mL conical flask, standing at 30 ℃ for 15 min to prepare AuNBs growth solution, adding 0.1 mL of 100mM ascorbic acid solution, conventionally stirring for 30 s, adding 10 mu L of gold nanoparticle solution, conventionally stirring for 30 s, and then standing at 30 ℃ for 12 h overnight to grow AuNBs; finally, centrifuging at 10000 rpm for 5min to remove the surfactant, washing with PBS for 2 times, adding water for resuspension, and storing the obtained AuNBs solution (2 mg/mL) at 4 ℃ for further experiments; 1mg of AuNBs (0.5 mL, 2 mg/mL) was added to dopamine solution (2 mM, 1mL), adjusted to pH 8.5 with sodium hydroxide, sonicated (frequency 40 KHz, power 99W) for 20 min, and PDA wrapped to obtain AuNBs @ PDA.
FIG. 1 is a basic property characterization of AuNBs @ PDA nanocomposites prepared in example 1. For the synthesis of AuNBs @ PDA composite material, firstly, gold nano-bone (AuNBs) is synthesized by using a seed crystal growth method, as shown in a TEM result of figure 1A, the synthesized gold nano-bone has good size uniformity, the length is 44.2 +/-1.4 nm, the middle diameter is 18.7 +/-1.4 nm, and the diameters of two ends are larger than the middle diameter. And after centrifugal separation of CTAC, carrying out self-polymerization reaction on the surface of the gold nano-particles by dopamine to form the AuNBs @ PDA composite material. As shown by the TEM results of FIG. 1B, the polydopamine layer thickness was 8. + -. 0.2 nm. Then, an ultraviolet spectrophotometer is used for detecting the light absorption conditions of AuNBs and AuNBs @ PDA, as shown in figure 1C, the AuNBs have two light absorption peaks which are respectively positioned at 552 nm and 667 nm of a visible light region, and the light absorption peak value of the AuNBs @ PDA is red-shifted, which is shown in that the AuNBs and the AuNBs @ PDA have obvious light absorption capacity in a near infrared region; and simultaneously, a dynamic light scattering instrument is used for characterizing the hydration particle size, the surface potential and the stability research of the nano material, as shown in figure 1D & F, an AuNBs hydration particle size curve has peaks at 56.2 nm and 3.4 nm, the surface potential is 28.0 +/-1.6 mV, and the AuNBs @ PDA hydration particle size peak is 150.9 nm, and the surface potential is-12.6 +/-2.5 mV. And AuNBs @ PDA was dimensionally stable within two days in PBS or DMEM medium containing 10% FBS (FIG. 1E).
Example 2 photothermal Properties of AuNBs @ PDA nanocomposites
Measurement of photothermal Properties of AuNBs @ PDA nanocomposites various concentrations of aqueous AuNBs @ PDA nanocomposite dispersions (0, 12.5, 25, 50, 100. mu.g/mL) obtained in example 1 were subjected to 808 nm laser irradiation (1W/cm)2) For 5 minutes. At the same time, 50 mu g/mL AuNBs @ PDA nano-composite aqueous solution is irradiated by different radiation power densities (0, 0.25, 0.5 and 0.75W/cm)2) 808 nm laser irradiation for 5 minutes. The initial temperature was maintained at 25 ℃. During irradiation, real-time temperature of AuNBs @ PDA nanocomposites was measured using an infrared thermal imager and distilled water as a control.
Fig. 2 is a representation of the photothermal properties of AuNBs @ PDA nanocomposites. As shown in FIG. 2A, the temperature raising effect of the solution is more obvious as the concentration of the AuNBs @ PDA composite material is increased, and when the concentration is 50 mug/mL, the temperature of the solution can be raised to about 60 ℃, and distilled water is used as a control group. Meanwhile, after irradiating 50 μ g/mL AuNBs @ PDA composite material with lasers with different powers at 808 nm for 5 minutes, the temperature of the solution also increased with increasing power (FIG. 2B).
In addition, 1mL of 50. mu.g/mL aqueous AuNBs @ PDA composite dispersion was irradiated with 808 nm laser (1W/cm)2) After 5 minutes, the laser is turned off, cooled naturally to about room temperature, and then turned on. As shown in fig. 2C, after four cycles of laser switching, the material temperature-rising effect is still good, which indicates that the temperature-rising stability of the material is good.
The photothermal conversion efficiency eta of the AuNBs @ PDA composite material obtained by calculation according to the existing formula (1) is as high as 75%, which is higher than that of the currently reported poly-dopamine-coated gold nano material (figure 2D). (the currently reported photothermal conversion efficiency of the gold nano material coated with polydopamine is shown in the following:Small,14, 2018, 1703077, η = 62 %;PDA nanoparticles (Acta Biomaterialia, 47 ,2017, 124, η = 39.3 %;RSC Advances, 39, 2016, 33083, η = 17 %)
Figure 581906DEST_PATH_IMAGE001
comparative example
On the basis of example 1, standing at 30 ℃ for 12 h overnight, adjusting the growth AuNBs to be standing at 30 ℃ for 8h, growing the AuNBs, and keeping the rest unchanged to obtain the Au @ PDA composite material with the photothermal conversion efficiency eta of 65.8%.
AgNO is added to the mixture of example 13The concentration of the solution was adjusted to 10mM, and the remainder was unchanged, so that the photothermal conversion efficiency eta of the Au @ PDA composite material was 61.2%.
Based on example 1, the addition amount of the gold nanoparticle solution was adjusted to 15 μ L, and the remainder was unchanged, so that the photothermal conversion efficiency η of the Au @ PDA composite material was 62.1%.
Example 3 Adriamycin (DOX) Loading and drug Release Using AuNBs @ PDA composite
AuNBs @ PDA composite Supported DOX: adding DOX aqueous solutions (0, 25, 50, 100, 150, 200 and 250 mug/mL) with different concentrations into 1mg/mL AuNBs @ PDA nano-composite aqueous solution prepared in example 1 respectively, stirring for 6 h at 25 ℃ in the dark, centrifugally washing for 3 times at 2000rpm of deionized water, and removing redundant DOX; the obtained DOX-loaded nano composite (AuNBs @ PDA/DOX) is resuspended in deionized water and stored at 4 ℃ for subsequent experiments, and the dosing effect is calculated by an ultraviolet-visible-near infrared absorbance method.
AuNBs @ PDA composite Release DOX: AuNBs @ PDA/DOX nanocomplexes were dialyzed against PBS buffer at pH 7.2 and pH 6. Doses released by AuNBs @ PDA/DOX nanocomplexes were collected and calculated at 0, 0.25, 0.5, 1, 3, 5, 7, 9, 11 and 24 hour time points. In addition, AuNBs @ PDA/DOX nanocomposites in pH6 solution were irradiated with near infrared laser (808 nm, 1W/cm2) for 5min at different time points, collected and the degree of release calculated.
As shown in fig. 3A, the chemical DOX has a characteristic absorption peak around 550 nm in visible light, and the light absorption value is proportional to the concentration. The DOX loading rate of AuNBs @ PDA composite was then examined and as shown in FIG. 3B, the loading rate increased with increasing DOX content for a given amount of composite. And the release of the drug has low pH and laser irradiation responsiveness, the release rate can reach 40% at pH6, and the DOX release rate can be increased to more than 60% after the laser irradiation temperature is increased (figure 3C).
Example 4 AuNBs @ PDA composite CT imaging and photoacoustic imaging
AuNBs @ PDA composite CT imaging: in vitro CT imaging, AuNBs @ PDA nanocomplex aqueous solutions (0, 62.5, 125, 250, 500, and 1000. mu.g/mL) at different concentrations were added to 1mL centrifuge tubes; iodoamide at the same concentration was used as a control.
AuNBs @ PDA composite photoacoustic imaging: the small animal imaging system MSOT was used for in vitro PA imaging, and in vitro assay evaluations were performed with various concentrations of AuNBs @ PDA nanocomposite aqueous solutions (0, 6.25, 12.5, 25, 50, and 100. mu.g/mL).
As shown in fig. 4A, as the concentration of the AuNBs @ PDA composite material increases, the CT signal gradually increases, and under the same concentration of the gold element and the iodine element, the CT imaging performance of the AuNBs @ PDA composite material is better than that of clinical iopromide, and the CT signal intensity is in direct proportion to the material concentration. As shown in fig. 4B, the photoacoustic signal gradually increased with increasing concentration of the AuNBs @ PDA composite. And the strength of the photoacoustic signal is in direct proportion to the concentration of the material.
Example 5 AuNBs @ PDA/DOX composite photothermal and chemical combination tumor therapy
Discussing the tumor photothermal and chemical combined treatment efficiency of the AuNBs @ PDA/DOX composite material: mouse breast cancer cell 4T1 at density 5X 103The cells were seeded in 96-well plates and incubated at different concentrations of free DOX, AuNBs @ PDA and AuNBs @ PDA/DOX, after 24 hours, and then exposed to a laser (1W/cm) at a wavelength of 808 nm2) For 5 minutes. Relative cell viability was determined for the different treated groups using the MTT cell proliferation kit and compared to the untreated control group. Fluorescence microscope dead and live staining analysis is used for further detecting the photothermal chemical synergistic treatment effect: 4T1 cells at 5X 10 per well4The density of individual cells was seeded in 12-well plates. After 24 h incubation, cells were divided into 6 groups (control, free DOX, AuNBs @ PDA/DOX, AuNBs @ PDA + NIR, AuNBs @ PDA/DOX + NIR). NIR = 808 nm laser, 1W/cm2, 5 min, CDOX = 6.6 μg/mL, CAuNBs@PDA= 50 μ g/mL), as aboveMTT experimental treatment. After treatment, the cells were stained with a dead and live cell staining kit for 30 min and observed by confocal microscopy. Live cells are green and dead cells are red.
As can be seen from fig. 5A, the cytotoxicity of AuNBs @ PDA nanocomplexes was insignificant in 4T1 cells, even when 50 μ g/mL was reached, indicating that AuNBs @ PDA nanocomplexes had good biocompatibility. However, after the AuNBs @ PDA nano-composite with the same concentration is irradiated by laser with the wavelength of 808 nm (1W/cm 2) for 5 minutes, the cell survival rate is obviously reduced, and the AuNBs @ PDA nano-composite can be used as an excellent tumor photothermal nano-preparation. As shown in fig. 5B, AuNBs @ PDA/DOX nanocomplexes have similar cytotoxicity to free DOX at the same DOX amount. As shown in fig. 5C, the combination treatment significantly reduced cell survival over both monotherapies. Particularly, when the DOX concentration is 6.6 mol/mL, the cell survival rate is reduced to 8%. The result shows that the AuNBs @ PDA/DOX nano-composite has good synergistic chemophotothermal treatment effect. As shown in fig. 5D, cells treated with AuNBs @ PDA nanocomplex alone had little cell death compared to the control group. In contrast, AuNBs @ PDA/DOX nanocomposites were the most cytotoxic in the laser irradiated group, consistent with the MTT method. The AuNBs @ PDA/DOX nano-composite has excellent tumor photothermal chemosynergistic treatment effect in vitro.
It is well known that malignant tumors present a serious threat to human life health. Therefore, how to realize early diagnosis and early treatment of tumors is a major issue of attention by medical and scientists. Currently, a large number of monotherapies are applied to malignant tumors. However, clinical practice proves that the single treatment methods have respective limitations due to the characteristics of invasive growth and easy metastasis of tumor cells, and the tumor cannot be completely removed by using only the single tumor treatment method. Therefore, the realization of a combination therapy of tumors by combining the advantages of different therapeutic means has become an important issue in the field of cancer therapy at present. The novel polydopamine-coated gold nano-bone (AuNBs @ PDA) composite material has excellent biocompatibility and strong adhesive property, can be easily combined with various other biomolecules, metal ions and polymer molecules, further has high drug loading efficiency, has excellent photo-thermal heating property, can be used for photo-thermal treatment, is used as a general surface coating of a functional nano material, and realizes multi-modal cooperative combination treatment based on photo-thermal treatment, thereby improving the final treatment effect.

Claims (10)

1. The gold nano-composite coated with polydopamine is characterized in that the preparation method of the gold nano-composite coated with polydopamine comprises the steps of mixing a chloroauric acid solution and a hexadecyl trimethyl ammonium chloride solution at room temperature, and then adding a sodium borohydride solution for reaction to prepare a gold nano seed solution; adding the gold nano seed solution into a mixed solution consisting of a chloroauric acid solution, a hexadecyltrimethylammonium chloride solution, a hydrochloric acid solution, a silver nitrate solution and an ascorbic acid solution, standing, and then carrying out ultrafiltration centrifugation, washing and water adding for heavy suspension to prepare a gold nano bone solution; and mixing the gold nano bone solution with a dopamine hydrochloride solution, and carrying out ultrasonic treatment to obtain the gold nano composite coated with polydopamine.
2. The polydopamine-coated gold nanocomposite as claimed in claim 1, wherein, when preparing the gold nanophase solution, the concentration of chloroauric acid solution is 10mM, the concentration of cetyltrimethylammonium chloride solution is 0.1M, and the concentration of sodium borohydride solution is 10 mM; the volume ratio of the chloroauric acid solution to the hexadecyl trimethyl ammonium chloride solution to the sodium borohydride solution is (0.4-0.6) to 10 to (0.5-0.7); the reaction time is 1-3 hours.
3. The polydopamine-coated gold nanocomposite as claimed in claim 1, wherein, when preparing the gold nanobead mother liquor, the concentration of the chloroauric acid solution is 10mM, the concentration of the cetyltrimethylammonium chloride solution is 0.1M, the concentration of the hydrochloric acid solution is 1mM, the concentration of the silver nitrate solution is 3mM, and the concentration of the ascorbic acid solution is 100 mM; the volume ratio of the hexadecyl trimethyl ammonium chloride solution to the silver nitrate solution to the hydrochloric acid solution to the chloroauric acid solution to the ascorbic acid solution to the gold nanoparticle seed solution is 10 to (0.08-0.12) to (0.15-0.25) to (0.4-0.6) to (0.05-0.15) to (0.009-0.011).
4. The polydopamine-coated gold nanocomposite as claimed in claim 1, wherein a cetyltrimethylammonium chloride solution, a silver nitrate solution, a hydrochloric acid solution and a chloroauric acid solution are mixed and then are allowed to stand for 10-20 minutes, and then an ascorbic acid solution and a gold nanoparticle solution are added; and then standing for 10-15 hours.
5. The polydopamine-coated gold nanocomposite as claimed in claim 1, wherein the ratio of the amount of the gold nanobody to the dopamine hydrochloride solution is 1 mg: 0.8-1.2 ml; the concentration of the dopamine hydrochloride solution is 2 mM.
6. A nanometer medicine is prepared by loading a small molecular medicine on a polydopamine-coated gold nanometer compound, and is characterized in that the preparation method of the polydopamine-coated gold nanometer compound comprises the steps of mixing a chloroauric acid solution and a hexadecyltrimethylammonium chloride solution at room temperature, and then adding a sodium borohydride solution for reaction to prepare a gold nanometer seed solution; adding the gold nano seed solution into a mixed solution consisting of a chloroauric acid solution, a hexadecyltrimethylammonium chloride solution, a hydrochloric acid solution, a silver nitrate solution and an ascorbic acid solution, standing, and then carrying out ultrafiltration centrifugation, washing and water adding for heavy suspension to prepare a gold nano bone solution; and mixing the gold nano bone solution with a dopamine hydrochloride solution, and carrying out ultrasonic treatment to obtain the gold nano composite coated with polydopamine.
7. The nano-drug according to claim 6, wherein the gold nano-bone solution is mixed with dopamine hydrochloride solution, the pH is adjusted to 8.5, and ultrasonic treatment is performed for 15-25 min to obtain the poly-dopamine coated gold nano-composite.
8. The nano-drug of claim 6, wherein the small molecule drug is a small molecule anti-tumor drug.
9. The application of the polydopamine-coated gold nanocomposite of claim 1 in loading small molecule drugs, or in preparing small molecule drug carriers, or in preparing nano drugs, or in preparing photo-thermal agents; or the application in the preparation of CT imaging reagents, or the application in the preparation of photoacoustic imaging reagents, or the application in the preparation of tumor treatment drugs; or the use of the nano-drug of claim 6 in the preparation of a medicament for the treatment of tumors.
10. The use of claim 9, wherein the tumor treatment agent is a combination of chemotherapy and photothermal tumor treatment agent.
CN202110070188.7A 2021-01-19 2021-01-19 Polydopamine-coated gold nano-composite, preparation method thereof and application thereof in multi-modal tumor diagnosis and treatment Pending CN112641946A (en)

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CN112143499A (en) * 2020-08-25 2020-12-29 上海大学 Diagnosis and treatment integrated rare earth luminescent nano diagnosis and treatment agent, preparation method and application thereof
CN112143499B (en) * 2020-08-25 2023-06-16 上海大学 Diagnosis and treatment integrated rare earth luminescent nano diagnosis and treatment agent, preparation method and application thereof
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CN113730600A (en) * 2021-08-24 2021-12-03 上海大学 Palladium-gold alloy diagnosis and treatment integrated nano composite system, preparation method and application thereof
CN114392236A (en) * 2022-01-10 2022-04-26 自然资源部第三海洋研究所 Co-doped dopamine-nano elemental selenium composition and preparation method thereof
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CN114558142A (en) * 2022-01-24 2022-05-31 华东理工大学 Poly-dopamine-based nano-drug responding to glutathione as well as preparation method and application thereof
CN115466602A (en) * 2022-10-20 2022-12-13 西南大学 AuNSs in-situ synthesis and application method based on seed-mediated method and portable thermometer

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