CN111330024B - Iron-based tumor diagnosis and treatment nano material based on hyaluronic acid and polyphenol as well as preparation method and application thereof - Google Patents

Iron-based tumor diagnosis and treatment nano material based on hyaluronic acid and polyphenol as well as preparation method and application thereof Download PDF

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CN111330024B
CN111330024B CN202010050290.6A CN202010050290A CN111330024B CN 111330024 B CN111330024 B CN 111330024B CN 202010050290 A CN202010050290 A CN 202010050290A CN 111330024 B CN111330024 B CN 111330024B
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hyaluronic acid
iron
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tumor
polyphenol
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CN111330024A (en
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唐建斌
徐晓丹
周晓璇
肖冰
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Zhejiang University ZJU
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    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K49/00—Preparations for testing in vivo
    • A61K49/06—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations
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    • A61K49/1818—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by a special physical form, e.g. emulsions, microcapsules, liposomes particles, e.g. uncoated or non-functionalised microparticles or nanoparticles
    • A61K49/1821—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by a special physical form, e.g. emulsions, microcapsules, liposomes particles, e.g. uncoated or non-functionalised microparticles or nanoparticles coated or functionalised microparticles or nanoparticles
    • A61K49/1824—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by a special physical form, e.g. emulsions, microcapsules, liposomes particles, e.g. uncoated or non-functionalised microparticles or nanoparticles coated or functionalised microparticles or nanoparticles coated or functionalised nanoparticles
    • A61K49/1827—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by a special physical form, e.g. emulsions, microcapsules, liposomes particles, e.g. uncoated or non-functionalised microparticles or nanoparticles coated or functionalised microparticles or nanoparticles coated or functionalised nanoparticles having a (super)(para)magnetic core, being a solid MRI-active material, e.g. magnetite, or composed of a plurality of MRI-active, organic agents, e.g. Gd-chelates, or nuclei, e.g. Eu3+, encapsulated or entrapped in the core of the coated or functionalised nanoparticle
    • A61K49/1851—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by a special physical form, e.g. emulsions, microcapsules, liposomes particles, e.g. uncoated or non-functionalised microparticles or nanoparticles coated or functionalised microparticles or nanoparticles coated or functionalised nanoparticles having a (super)(para)magnetic core, being a solid MRI-active material, e.g. magnetite, or composed of a plurality of MRI-active, organic agents, e.g. Gd-chelates, or nuclei, e.g. Eu3+, encapsulated or entrapped in the core of the coated or functionalised nanoparticle having a (super)(para)magnetic core coated or functionalised with an organic macromolecular compound, i.e. oligomeric, polymeric, dendrimeric organic molecule
    • A61K49/1863—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by a special physical form, e.g. emulsions, microcapsules, liposomes particles, e.g. uncoated or non-functionalised microparticles or nanoparticles coated or functionalised microparticles or nanoparticles coated or functionalised nanoparticles having a (super)(para)magnetic core, being a solid MRI-active material, e.g. magnetite, or composed of a plurality of MRI-active, organic agents, e.g. Gd-chelates, or nuclei, e.g. Eu3+, encapsulated or entrapped in the core of the coated or functionalised nanoparticle having a (super)(para)magnetic core coated or functionalised with an organic macromolecular compound, i.e. oligomeric, polymeric, dendrimeric organic molecule the organic macromolecular compound being a polysaccharide or derivative thereof, e.g. chitosan, chitin, cellulose, pectin, starch
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    • A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
    • A61K41/0052—Thermotherapy; Hyperthermia; Magnetic induction; Induction heating therapy
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K49/00—Preparations for testing in vivo
    • A61K49/06—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations
    • A61K49/08—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by the carrier
    • A61K49/10—Organic compounds
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Abstract

The invention discloses an iron-based nano material based on hyaluronic acid and polyphenol, a preparation method and application thereof. The high-efficiency iron-based nano-scale macromolecular contrast agent is prepared by an oxidation self-assembly method, has the advantages of high relaxation efficiency of T1 and T2 and the like, and can be used as a tumor contrast agent and a liver contrast agent; in addition, the nano material has better photothermal conversion performance in a near infrared region, can be used as a photothermal therapeutic agent to be applied to photothermal therapy, monitors the position and the size of a tumor and the enrichment condition of the photothermal therapeutic agent in tumor tissues in real time through a magnetic resonance imaging device, is used for evaluating the curative effect of the tumor therapy to guide prognosis, and realizes the integration of photothermal therapy diagnosis and treatment mediated by magnetic resonance imaging.

Description

Iron-based tumor diagnosis and treatment nano material based on hyaluronic acid and polyphenol as well as preparation method and application thereof
Technical Field
The invention relates to the field of magnetic resonance imaging-mediated photothermal therapy diagnosis and treatment integrated materials, in particular to an iron-based tumor diagnosis and treatment nano material based on hyaluronic acid and polyphenol and a preparation method and application thereof.
Background
Integration of diagnosis and treatment is an emerging strategy for promoting tumor therapy that tightly combines diagnostic and therapeutic functions, which allows real-time monitoring of drug delivery and efficacy in diseased tissues, where Magnetic Resonance Imaging (MRI) guided photothermal therapy (PTT) has been studied by many researchers to achieve optimal tumor therapy. This is because the inaccurate localization of the small tumor involved in PTT or incomplete ablation of the tumor may cause tumor recurrence, affecting the therapeutic effect and limiting its application, while MRI can be widely used for imaging soft tissues and identifying the available information of the location, shape, size, etc. of the tumor with high resolution and without radiation damage, so the combination of PTT and MRI can greatly improve the accuracy and effectiveness of tumor therapy and make effective evaluation and prognosis.
The photo-thermal therapeutic agent is a reagent which can convert light energy into heat energy under the condition of near-infrared illumination to cause local high temperature of a tumor so as to kill cancer cells, wherein metal nano-materials, carbon nano-materials, inorganic nano-particles, polydopamine and other organic nano-particles are developed to be used for the photo-thermal therapy of the tumor. Since near infrared light is most permeable to biological tissues, an ideal photothermal therapeutic should have strong absorption in the near infrared region (650-950 nm).
Magnetic resonance contrast agents (MRI contrast agents) are a class of agents used to assist MRI imaging in the hope of enhancing signal contrast and improving resolution box sensitivity of soft tissue images. The magnetic resonance imaging T1 contrast agent is generally a paramagnetic gadolinium contrast agent, and a small molecule contrast agent such as Magnevist (gadolinium meglumine injection) which is commonly used in clinic at present is adopted. However, the small molecule contrast agent is easy to be rapidly eliminated after being metabolized by the kidney, has low relaxation rate, and is easy to cause toxic and side effects such as renal fibrosis, brain accumulation and the like. While the iron-based contrast agent has relatively high and better biocompatibility due to the endogenesis of iron element, the iron-based contrast agent such as the fertix magnet which is clinically used at present is generally used for magnetic resonance T2 weighted imaging. The nanoscale macromolecular iron-based contrast agent which has high relaxation rate, high contrast intensity, T1/T2 imaging, long circulation in vivo and high biological safety is further developed, and the nanoscale macromolecular iron-based contrast agent brings better clinical medical prospect.
Therefore, it is a problem to be solved by those skilled in the art to develop a new nano material that can be used as both a contrast agent for magnetic resonance imaging and photothermal therapy, i.e. to satisfy the above-mentioned objective of integrating high-efficiency magnetic resonance imaging and photothermal therapy.
Disclosure of Invention
The invention aims to provide a novel nano material, a preparation method and application thereof, the nano material is prepared by spontaneous oxidation of dopamine-grafted hyaluronic acid (HADA), polyphenol compounds and iron salts, has higher relaxation rate and higher photothermal conversion efficiency under the condition of near-infrared illumination, and can be used as a magnetic resonance contrast agent and a photothermal therapeutic agent to be applied to magnetic resonance imaging and photothermal therapy.
In order to achieve the purpose, the invention adopts the following technical scheme: a method of preparing a nanomaterial comprising: the dopamine-grafted hyaluronic acid, the polyphenol compound and the ferric salt are added into an aqueous medium, and the nano material with the functions of the magnetic resonance imaging contrast agent and the photothermal therapy is prepared by oxidation at room temperature under the alkaline condition.
In the preparation method, ferrous ions are oxidized into ferroferric oxide under the alkaline condition; the polyphenol compound can reduce iron ions, partial phenolic groups in the polyphenol compound are oxidized into semiquinone or quinone with higher activity, a polymer network is formed by crosslinking, and the generated ferroferric oxide particles are stabilized and self-assembled to form the nano material under the protection of hyaluronic acid.
Preferably, the dopamine is dopamine hydrochloride, 6-hydroxydopamine hydrobromide, levodopa and the like, and the dopamine hydrochloride is more preferably represented by the following molecular formula: c8H12ClO2N, molecular weight: 189.64, CAS number: 62-31-7, which has a structural formula shown as the following formula (I):
Figure 435676DEST_PATH_IMAGE002
(I)。
preferably, the hyaluronic acid is sodium hyaluronate with a molecular weight of 10k-40 k.
Preferably, the grafting ratio of the dopamine-grafted hyaluronic acid is 10-60%. Experiments show that when the dopamine grafting rate is less than 38%, nanoparticles cannot be prepared; when the grafting rate of dopamine is more than 60%, HADA is easier to oxidize, and the contrast effect of the prepared nano-particles is poor.
Preferably, the polyphenol compound is tannic acid, gallic acid, epigallocatechin, or the like.
Preferably, the iron salt is ferrous sulfate, ferrous phosphate, ferrous chloride, or the like.
Preferably, the mass concentration of the dopamine grafted hyaluronic acid in the mixture is 1-5mg/mL, the mass concentration of the polyphenol compound in the mixture is preferably tannic acid and is 0.1-0.5mg/mL, and the mass concentration of the iron salt in the mixture is preferably ferrous sulfate and is 0.3-1.5 mg/mL.
Preferably, the mixture is reacted under alkaline conditions of pH >10, and when the solution pH is less than 10, the resulting nanoparticle size distribution is poor.
The preparation method of the invention also comprises the following steps: after the dopamine-grafted hyaluronic acid, the polyphenol compound and the ferric salt are oxidized to prepare the nano material, the nano material is intercepted by a dialysis membrane, and then the nano material with corresponding concentration is obtained by freeze drying or centrifugal concentration by an ultrafiltration tube.
The invention provides a nano material prepared by the preparation method, wherein the mass percent of iron in the nano material is 2-3%. The iron content of the nano material needs to reach a certain amount to achieve the contrast effect.
The particle size of the nano material prepared by the invention is within the range of 60-400 nm, and the nano material can be stable for seven days in deionized water, normal saline, PBS and RMPI-1640 culture medium, and the color is dark brown.
The iron-based nano macromolecular contrast agent is prepared by an extremely simple oxidation self-assembly method, the nano material can be enriched in tumor tissues through a high permeability long retention (EPR) effect, the sensitivity of magnetic resonance imaging is improved, the diagnosis level of early cancer is improved, and the weighted imaging capability of the nano material T1/T2 can be used as a liver specific contrast agent.
The nano material prepared by the invention has a certain amount of absorption in a near-infrared region with the wavelength of 650-950nm, and researches show that the nano material is applied to tumor cells, and the proliferation of the tumor cells is inhibited under the condition of near-infrared illumination (808 nm), so that the nano material can be used as a photo-thermal therapeutic agent.
The invention also provides application of the nano material in preparation of a magnetic resonance imaging contrast agent and/or a photothermal therapeutic agent.
The invention has the following beneficial effects:
(1) the invention prepares the iron-based nano material by self-assembly under air oxidation through an oxidation self-assembly method, and the nano material as a nano-scale macromolecular contrast agent has the advantages of capability of weighting magnetic resonance imaging of T1 and T2 simultaneously, long in-vivo circulation time, high biocompatibility, small toxic and side effects and the like.
(2) The nano material prepared by the invention has higher photothermal conversion efficiency in a near infrared region, can be used as a photothermal therapeutic agent to be applied to photothermal therapy, and additionally monitors the position and the size of a tumor and the enrichment condition of the photothermal therapeutic agent in tumor tissues by means of a magnetic resonance technology, is used for evaluating the treatment effect, and realizes the photothermal therapy diagnosis and treatment integration mediated by magnetic resonance imaging.
Drawings
FIG. 1 is the imaging diagram of the in vitro magnetic resonance imaging of the nano-material at various concentrations, wherein the images are the contrast of the nano-material aqueous solution at the concentrations of water, 0.05mM, 0.10 mM, 0.15mM, 0.2 mM, 0.5mM, 1mM, 2mM, 3 mM, 4 mM and 5mM respectively.
Fig. 2 is an image of magnetic resonance imaging of breast tumor enhanced by nanomaterials and Magnevist (Magnevist) as T1 magnetic resonance contrast agent and a signal intensity quantification image, wherein (a) the image of breast tumor inoculated by nanomaterials and Magnevist (Magnevist) in 4T1 cells; (B) nanomaterial and Magnevist post injection tumor (tumor) and normal tissue (normal tissue) signal intensity plots.
FIG. 3 is a graph showing the absorption in the near infrared region for various concentrations of nanomaterials.
FIG. 4 is a graph showing the effect of the nano-material on the proliferation of 4T1 cells under the irradiation of near infrared light or not (the optical power density is 2W/cm)2808 nm near infrared illumination for 5 minutes).
FIG. 5 is a tumor growth curve diagram of the nano-material in the inhibition experiment of the 4T1 breast cancer cell-bearing Balb/c mouse tumor.
Fig. 6 is a graph showing the proliferation effect of the nanomaterials on a549 cells and HepG2 cells in the absence of laser irradiation.
FIG. 7 is a graph showing the change of body weight of Balb/c mice in the experiment process of inhibiting tumors of Balb/c mice with breast cancer cells of 4T1 by using the nano material.
FIG. 8 is a graph showing the particle size distribution of the synthesized nanomaterial of example 1 measured by dynamic light scattering in water.
FIG. 9 is a transmission electron micrograph of the nanomaterial synthesized in example 1.
FIG. 10 shows the relaxation rates of T1/T2 magnetic resonance contrast agents for the nanomaterials synthesized in example 1.
Detailed Description
Preparing a nano material: adding the dopamine grafted hyaluronic acid, the polyphenol compound and the iron salt into an aqueous medium to obtain a mixture, wherein the mass concentration of the dopamine grafted hyaluronic acid in the mixture is 1-5mg/mL, the mass concentration of the polyphenol compound is 0.1-0.5mg/mL, and the mass concentration of the iron salt is 0.3-1.5 mg/mL. And (2) reacting the mixture at room temperature under an alkaline condition, spontaneously assembling to form nano particles, dialyzing, and freeze-drying or ultrafiltering, centrifuging and concentrating to prepare the nano material, wherein the mass percent of iron in the nano material is 2-3%. The nano material has better magnetic resonance imaging and photo-thermal properties;
as shown in FIG. 1, the signal value of water is very weak, the image is very dim, the image of the nano material is brighter when the nano material is used as a T1 contrast agent in a certain concentration range, and the image of the T2 contrast agent is darker along with the increase of the concentration, so that the T1/T2 imaging efficiency can be more excellent.
As shown in fig. 2, (a) imaging of breast tumors seeded with nanomaterials and clinical Magnevist (Magnevist) in 4T1 cells. Experiments show that compared with Magnevist, the nano material shows obvious contrast strength and a durable contrast time window at a tumor part. (B) Nano material and clinical Magnevist (Magnevist) signal intensity maps in tumor (tumor) and normal tissue (normal tissue). Experiments show that compared with Magnevist, after the nano material is injected, the signal intensity of the tumor is always increased within 60 minutes, and the signal intensity reaches a peak value within 60 minutes, so that a clearer and more accurate diagnosis window can be provided for breast tumors.
As shown in fig. 3, the nanomaterial is strongly absorbed in the near infrared region and is concentration-dependent.
As shown in fig. 4, when the cell incubation nanomaterial is not irradiated by laser, the cell survival rate is higher, and when the cell incubation nanomaterial is irradiated by laser, the cell survival rate decreases with the increase of the concentration of the nanomaterial, which indicates that the nanomaterial can convert light energy into heat energy to kill tumor cells under near-infrared irradiation, and has the potential of being applied to photothermal therapy.
As shown in fig. 5, after the breast tumor inoculated with 4T1 cells was treated once, the tumors of the three control groups (PBS group, nanomaterial group, light-only group) all showed the same tumor growth trend, indicating that the growth of the tumor could not be inhibited by nanomaterial alone or light itself. The tumor of the experimental group (the nano material and the illumination) disappears after the laser irradiation, which shows that the nano material is suitable for being used as a photo-thermal reagent to be applied to the photo-thermal treatment of the tumor.
As shown in fig. 6, the survival rate of the a549 cells and the HepG2 cells after the incubation of the nano material is high, which indicates that the nano material has no significant influence on the proliferation capacity of the cells, and proves that the nano material has low cytotoxicity.
As shown in fig. 7, the body weight of the mice did not change significantly during the treatment period (2 weeks), indicating that the nanomaterial has no significant toxicity to the mice and high biological safety.
The present invention will be further described with reference to the following specific examples.
Example 1
1. Preparation of nanomaterials
(1) 10 mg of HADA (hyaluronic acid molecular weight 40k, dopamine graft ratio 38%), 1 mg of tannic acid and 8.3 mg of ferrous sulfate were added to 10 mL of deionized water, and then sodium hydroxide was added dropwise to adjust the pH of the solution to 12.
(2) Dialyzing, and freeze-drying or ultrafiltering, centrifuging and concentrating to obtain nanometer material.
2. Analysis of Properties of nanomaterials
As shown in fig. 8, the average particle size of the nanomaterials was 61 nm as measured by Dynamic Light Scattering (DLS).
As shown in fig. 9, the particle size of the nanomaterial observed by Transmission Electron Microscopy (TEM) was around 60 nm, which is consistent with the particle size results obtained by DLS.
As shown in figure 10, the iron content of the nano material is 2.3 percent by mass, and the relaxation rate R is1A value of 41.91mM-1·s-1，R2A value of 118.93 mM-1·s-1。
Example 2
10 mg of HADA (hyaluronic acid molecular weight 40k, dopamine graft ratio 38%), 3 mg of tannic acid and 8.3 mg of ferrous sulfate were added to 10 mL of deionized water, and then sodium hydroxide was added dropwise to adjust the pH of the solution to 12. Dialyzing, and freeze-drying or ultrafiltering, centrifuging and concentrating to obtain nanometer material. The average particle size of the nano material is 109 nm, wherein the mass percent of iron is 2.1%.
Example 3
10 mg of HADA (hyaluronic acid molecular weight 40k, dopamine graft ratio 38%), 5mg of tannic acid and 8.3 mg of ferrous sulfate were added to 10 mL of deionized water, and then sodium hydroxide was added dropwise to adjust the pH of the solution to 12. Dialyzing, and freeze-drying or ultrafiltering, centrifuging and concentrating to obtain nanometer material. The average particle size of the nano material is 213.5 nm, wherein the mass percent of iron is 2.0%.
Example 4
10 mg of HADA (hyaluronic acid molecular weight 40k, dopamine graft ratio 38%), 1 mg of tannic acid and 3 mg of ferrous sulfate were added to 10 mL of deionized water, and then sodium hydroxide was added dropwise to adjust the pH of the solution to 12. Dialyzing, and freeze-drying or ultrafiltering, centrifuging and concentrating to obtain nanometer material. The average particle size of the nano material is 85 nm, wherein the mass percent of iron is 2.5%.
Example 5
10 mg of HADA (hyaluronic acid molecular weight 40k, dopamine graft ratio 38%), 1 mg of tannic acid and 10 mg of ferrous sulfate were added to 10 mL of deionized water, and then sodium hydroxide was added dropwise to adjust the pH of the solution to 12. Dialyzing, and freeze-drying or ultrafiltering, centrifuging and concentrating to obtain nanometer material. The average particle size of the nano material is 200 nm, wherein the mass percent of iron is 2.6%.
Example 6
10 mg of HADA (hyaluronic acid molecular weight 10k, dopamine graft ratio 60%), 1 mg of tannic acid and 8.3 mg of ferrous sulfate were added to 10 mL of deionized water, and then sodium hydroxide was added dropwise to adjust the pH of the solution to 10. Dialyzing, and freeze-drying or ultrafiltering, centrifuging and concentrating to obtain nanometer material. The average particle size of the nano material is 95 nm, wherein the mass percent of iron is 2.2%.
Example 7
30 mg of HADA (hyaluronic acid molecular weight 40k, dopamine graft ratio 38%), 3 mg of tannic acid and 8.3 mg of ferrous sulfate were added to 10 mL of deionized water, and then sodium hydroxide was added dropwise to adjust the pH of the solution to 12. Dialyzing, and freeze-drying or ultrafiltering, centrifuging and concentrating to obtain nanometer material. The average particle size of the nano material is 137 nm, wherein the mass percent of iron is 2.2%.
Example 8
50 mg of HADA (hyaluronic acid molecular weight 40k, dopamine graft ratio 38%), 5mg of tannic acid and 8.3 mg of ferrous sulfate were added to 10 mL of deionized water, and then sodium hydroxide was added dropwise to adjust the pH of the solution to 12. Dialyzing, and freeze-drying or ultrafiltering, centrifuging and concentrating to obtain nanometer material. The average particle size of the nano material is 138 nm, wherein the mass percent of iron is 2.2%.
Example 9
10 mg of HADA (hyaluronic acid molecular weight 40k, dopamine grafting rate 38%), 5mg of epigallocatechin and 4 mg of ferrous chloride are added into 10 mL of deionized water, and then sodium hydroxide is added dropwise to adjust the pH value of the solution to 12. Dialyzing, and freeze-drying or ultrafiltering, centrifuging and concentrating to obtain nanometer material. The average particle size of the nano material is 376 nm, wherein the mass percent of iron is 2.8%.
Example 10
10 mg of HADA (hyaluronic acid molecular weight 40k, dopamine grafting rate 38%), 4 mg of gallic acid and 8.3 mg of ferrous sulfate were added to 10 mL of deionized water, and then sodium hydroxide was added dropwise to adjust the pH of the solution to 12. Dialyzing, and freeze-drying or ultrafiltering, centrifuging and concentrating to obtain nanometer material. The average particle size of the nano material is 174 nm, wherein the mass percent of iron is 2.9%.
Example 11
10 mg of HADA (hyaluronic acid molecular weight 40k, dopamine grafting rate 38%), 5mg of epigallocatechin and 8.3 mg of ferrous sulfate were added to 10 mL of deionized water, and then sodium hydroxide was added dropwise to adjust the pH of the solution to 12. Dialyzing, and freeze-drying or ultrafiltering, centrifuging and concentrating to obtain nanometer material. The average particle size of the nano material is 77 nm, wherein the mass percent of iron is 3.0%.
According to the embodiment, when the mass ratio of the dopamine grafted hyaluronic acid to the polyphenol compound to the iron salt in the mixture is not proper, the prepared nano material has the problem of overlarge size, and overlarge particles cannot be effectively enriched in tumor tissues through an EPR effect and are easily intercepted by a reticuloendothelial system, so that the nano material with the minimum particle size is suitable for being used as the magnetic resonance imaging contrast agent and the photothermal therapeutic agent.
The above-described embodiments are intended to illustrate rather than to limit the invention, and any modifications and variations of the present invention are within the spirit of the invention and the scope of the appended claims.

Claims (9)

1. A preparation method of an iron-based nano material based on hyaluronic acid and polyphenol is characterized in that dopamine grafted hyaluronic acid, polyphenol compounds and ferrous salt are added into an aqueous medium, oxidation-reduction reaction is carried out in the air, and a stable nano material with magnetic resonance imaging contrast agent and photothermal therapy functions is prepared by self-assembly.
2. The method according to claim 1, wherein the hyaluronic acid is sodium hyaluronate with a molecular weight of 10k to 40 k.
3. The method according to claim 1, wherein the grafting ratio of the dopamine-grafted hyaluronic acid is 38 to 60%.
4. The method according to claim 1, wherein the polyphenol compound is tannic acid, gallic acid or epigallocatechin.
5. The method of claim 1, wherein the iron salt is ferrous sulfate, ferrous phosphate, or ferrous chloride.
6. The method according to claim 1, wherein the dopamine grafted hyaluronic acid, the polyphenol compound and the iron salt are added to the aqueous medium to obtain a mixture, and the mass concentration of the dopamine grafted hyaluronic acid in the mixture is 1 to 5mg/mL, the mass concentration of the polyphenol compound is 0.1 to 0.5mg/mL, and the mass concentration of the iron salt is 0.3 to 1.5 mg/mL.
7. The method according to claim 6, wherein the dopamine-grafted hyaluronic acid, the polyphenol compound and the iron salt react in one step at room temperature under alkaline conditions, and the product is spontaneously assembled to form the nanomaterial.
8. A nano-material prepared by the preparation method of any one of claims 1 to 7, wherein the nano-material is prepared by stabilizing hyaluronic acid, polyphenol compounds and iron element through oxidation-reduction reaction.
9. Use of a nanomaterial as defined in claim 8 for the preparation of a magnetic resonance imaging T1 and/or T2 contrast agent and/or photothermal therapy agent.
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