CN113730600B - Palladium-gold alloy diagnosis and treatment integrated nano composite system, preparation method and application thereof - Google Patents
Palladium-gold alloy diagnosis and treatment integrated nano composite system, preparation method and application thereof Download PDFInfo
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- CN113730600B CN113730600B CN202110971564.XA CN202110971564A CN113730600B CN 113730600 B CN113730600 B CN 113730600B CN 202110971564 A CN202110971564 A CN 202110971564A CN 113730600 B CN113730600 B CN 113730600B
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Abstract
The invention discloses a palladium-gold alloy diagnosis and treatment integrated nano composite system, a preparation method and application thereof, wherein the system takes palladium-gold alloy nano particles as an inner core, dopamine monomers undergoing polymerization reaction form a polydopamine shell layer coated on the outer surface of the palladium-gold alloy nano particles, then the polydopamine layer is loaded with medicine 2,2' -azobis [2- (2-imidazoline-2-yl) propane ] dihydrochloride, and then Gd-protein complex is used for integrally coating a core-shell structure material after medicine loading to form an organic/inorganic hybrid nano biological material. The nano composite system provided by the invention has the advantages of high thermal stability, good biocompatibility and the like, has the functions of thermodynamic therapy and photothermal therapy, and can be applied to the field of the synergy therapy of the thermodynamic therapy and the photothermal therapy of cancers guided by multimode imaging such as magnetic resonance imaging, photoacoustic imaging, CT imaging and the like. The preparation method has the characteristics of mild and simple synthesis conditions, high repeatability and the like.
Description
Technical Field
The invention relates to the technical field of nano biological materials, in particular to a gadolinium complex modified palladium-gold alloy diagnosis and treatment integrated nano composite system, a preparation method and application thereof.
Background
According to the latest data published by the international cancer research Institute (IARC), recent data research shows that about 1930 ten thousand cancer cases are increased worldwide in 2020, and about 1000 ten thousand deaths are observed; according to statistics, the incidence and death rate of cancer cases in China show an annual rising trend. At present, most of clinically diagnosed cancer patients belong to middle and late stages, the optimal period of treatment is missed, and most doctors adopt a single operation treatment mode to resect tumors, so that the risk is high and the success rate is low. Therefore, if accurate diagnosis can be carried out at early stage of cancer and efficient treatment means can be assisted, the method has great promotion significance for the progress in the field of cancer treatment.
However, the imaging modes of the clinically definite cancer have certain technical defects, different imaging technical principles are different, and the response information has emphasis and respective advantages and disadvantages. For example, CT imaging, due to the strong penetrating power of X-rays, does not have obvious imaging effects on soft tissues, so that there is a lack of powerful judgment on some soft tissue lesions; the sensitivity of PET is high, and the PET is favorable for analyzing the distribution of drugs or probes in a living body, but the spatial resolution is lower; MRI is sensitive, but has low spatial resolution, and has poor imaging effect on certain early diseases, such as in early diagnosis of tumor, and can not distinguish tumor edges from normal tissues well. Therefore, researchers hope to develop a contrast agent integrating tumor multi-mode imaging technology, which is beneficial to integrating the advantages of different imaging modes and improving the early diagnosis rate of cancer.
Chinese invention patent application number: CN201210309662.8 discloses preparation and application of a gold-palladium core-shell material for constructing a lung cancer tumor marker immunosensor, which utilizes Au@Pd core-shell nano material, has the characteristics of large specific surface area, good biocompatibility, high catalytic efficiency and the like, and remarkably improves the sensitivity of the immunosensor. The gold-palladium core-shell material constructed lung cancer tumor marker immunosensor has the advantages of high sensitivity, good specificity and easy operation, can realize the sensitive, rapid and accurate detection of various lung cancer tumor markers in a serum sample, has important significance for early diagnosis of lung cancer, but does not have a therapeutic function.
The hypoxic microenvironment is one of the typical features of solid tumors, which is an imbalance between high oxygen consumption caused by rapid proliferation of tumor cells and inadequate oxygenation caused by malformation of tumor vasculature. Previous reports have demonstrated that cancer cells are extremely resistant to chemotherapy and oxygen-dependent photodynamic therapy in areas of tumor hypoxia. Therefore, an effective strategy is developed to overcome the tumor hypoxia microenvironment, and the accumulation of the biocompatible nano material at the tumor part is increased, so that the method has important significance for obtaining a good synergistic anticancer treatment effect.
Chemotherapy and radiation therapy are currently the two major approaches to clinically treating cancer, but neither of them often ablate tumors thoroughly. Chemotherapy is generally to inject a large amount of free drugs into a patient, but the free drugs have no specificity to tumors, so that only a small amount of drugs can reach the tumor focus area of the patient through blood circulation, and most of drugs are phagocytized by normal organs such as liver, spleen and the like, so that systemic toxic and side effects exist. Radiotherapy is used as a medical technology with century development history, and can effectively inhibit the local growth of malignant tumors; unfortunately, because there are generally hypoxic cells in the tumor that are insensitive to X-rays, a small amount of hypoxic cells left after the irradiation can cause local recurrence of the tumor, and at the same time, repeated irradiation with high dose X-rays is repeated for many times, which inevitably damages surrounding normal tissues, and eventually fails the radiotherapy. In addition to the treatment methods of chemotherapy and radiotherapy commonly used in clinic, as an emerging tumor treatment technology, photothermal therapy, photodynamic therapy and thermodynamic therapy are representative thereof, but single photothermal therapy is limited by the limited penetration depth of light, and photodynamic therapy rules can limit the generation of sufficient active oxygen due to tumor hypoxia, so that the effective killing effect is limited.
Disclosure of Invention
The invention aims at providing a gadolinium complex modified palladium-gold alloy diagnosis and treatment integrated nano composite system material, which is used for constructing a multifunctional tumor diagnosis and treatment integrated nano material combining a plurality of tumor treatment modes by taking multi-mode imaging as guidance through unique component and microstructure design, so that the material has the characteristics of magnetic resonance imaging, CT imaging and photoacoustic imaging, and multi-mode treatment, namely the characteristics of thermodynamic treatment and photothermal treatment of cancers, and provides a new strategy for the clinical multi-mode diagnosis and multi-mode treatment integrated field.
The invention also aims to provide a preparation method of the material, optimize the preparation process and have the characteristics of simple and mild synthesis conditions and high repeatability;
the invention also provides application of the material in integration of multi-mode imaging diagnosis and dual-mode treatment.
In order to achieve the above purpose, the invention adopts the following technical scheme:
the palladium-gold alloy diagnosis and treatment integrated nano composite system material is characterized in that palladium-gold alloy nano particles are taken as an inner core, dopamine monomers undergoing polymerization reaction form polydopamine shell layers coated on the outer surfaces of the palladium-gold alloy nano particles, then the polydopamine layers are used for loading medicine 2,2' -azobis [2- (2-imidazoline-2-yl) propane ] dihydrochloride, and then Gd-protein complexes are used for integrally coating the core-shell structure material after medicine loading to form an organic/inorganic hybrid nano biological material, namely a gadolinium complex modified palladium-gold alloy diagnosis and treatment integrated nano composite system.
The surface of the palladium-gold alloy nanoparticle is coated with a polydopamine layer, and the pi-pi interaction is utilized to load the medicine 2,2' -azobis [2- (2-imidazoline-2-yl) propane ] dihydrochloride.
The Gd-protein complex is as follows: one of Gd-bovine serum albumin complex (Gd-BSA) and Gd-human serum albumin complex (Gd-HSA).
The preparation method of the palladium-gold alloy diagnosis and treatment integrated nano composite system is characterized by comprising the following steps of:
(1) Preparing a first dispersion: preparing sodium citrate, aqueous solution of palladium chloride and aqueous solution of chloroauric acid, and surfactant Cetyl Trimethyl Ammonium Bromide (CTAB) and Cetyl Trimethyl Ammonium Chloride (CTAC) respectively, reducing the aqueous solution of palladium chloride and the aqueous solution of chloroauric acid by sodium citrate to synthesize palladium-gold alloy nano particles, and dispersing the palladium-gold alloy nano particles in deionized water; then adding dopamine monomer under alkaline condition, polymerizing to form polydopamine layer coated on the surface of palladium-gold alloy nano particle, ultrasonically dispersing, centrifuging, and dispersing solid in deionized water to form first dispersion;
(2) Preparing a second dispersion: preparing 2,2' -azo-bis [2- (2-imidazolin-2-yl) propane ] dihydrochloride, and dissolving the 2,2' -azo-bis [2- (2-imidazolin-2-yl) propane ] dihydrochloride in a set amount of deionized water to obtain 2,2' -azo-bis [2- (2-imidazolin-2-yl) propane ] dihydrochloride aqueous solution; mixing the 2,2' -azobis [2- (2-imidazoline-2-yl) propane ] dihydrochloride aqueous solution with a first dispersion liquid, stirring in a dark place within a set time at room temperature, centrifuging after ultrasonic dispersion, and dispersing the solid in deionized water to form a second dispersion liquid;
(3) Preparing a third dispersion: respectively preparing protein powder and gadolinium chloride (GdCl) 3 ) An aqueous solution, an aqueous sodium hydroxide solution; dissolving protein powder in deionized water at constant temperature, adding GdCl 3 Adding sodium hydroxide aqueous solution into the aqueous solution, continuously maintaining constant temperature, rapidly stirring, dialyzing with dialysis bag and deionized water to obtain Gd-protein complex, and forming a third dispersion;
(4) And (3) overall coating: mixing the second dispersion liquid and the third dispersion liquid according to a set proportion, stirring in a dark place at 15-25 ℃, performing ultrasonic dispersion after reaching a set time, centrifuging, taking the solid to disperse in deionized water, and enabling the Gd-protein complex to carry out integral coating on the core-shell structure material to form an organic/inorganic hybrid nano biological material, thereby obtaining the gadolinium complex modified palladium-gold alloy diagnosis and treatment integrated nano composite system material.
The specific steps for preparing the first dispersion liquid in the step (1) are as follows:
(1-1) preparing an aqueous solution of palladium chloride and an aqueous solution of chloroauric acid, respectively;
(1-2) uniformly mixing 44 ml of cetyltrimethylammonium bromide (CTAB) and 5 ml of cetyltrimethylammonium chloride (CTAC) surfactant, adding 10mmol/L of aqueous solution of palladium chloride and 1.2 ml of mixed solution of 10mmol/L of aqueous solution of chloroauric acid (the mol ratio of the palladium chloride to the chloroauric acid is 1:1-1:2), adding 200-250 mu L of sodium citrate with the concentration of 100mmol/L after 20 minutes, and preserving the temperature for 16-20 hours at the constant temperature of 80-100 ℃ under the airtight condition to synthesize palladium-gold alloy nano particles;
(1-3) dispersing palladium-gold alloy nano particles in 20 ml of deionized water, then adding 5 mg of dopamine monomer salt, polymerizing dopamine monomer under an alkaline condition with pH value of 9-12, coating the surface of the palladium-gold alloy nano particles to form a polydopamine layer, centrifuging at a speed of 13000-15000 rpm after ultrasonic dispersion, and dispersing the obtained solid in 20 ml of deionized water to form a first dispersion liquid.
The specific steps for preparing the second dispersion liquid in the step (2) are as follows:
(2-1) taking 0.1-0.2 g of 2,2 '-azobis [2- (2-imidazolin-2-yl) propane ] dihydrochloride, and dissolving the same in 5 ml of deionized water to obtain 2,2' -azobis [2- (2-imidazolin-2-yl) propane ] dihydrochloride aqueous solution;
(2-2) mixing the aqueous solution of 2,2' -azobis [2- (2-imidazolin-2-yl) propane ] dihydrochloride with the first dispersion liquid uniformly, stirring for 10-15 hours at room temperature in a dark place, centrifuging at a speed of 11000-13000 rpm after ultrasonic dispersion, and dispersing the solid in 20 ml of deionized water to form a second dispersion liquid.
The specific steps for preparing the third dispersion liquid in the step (3) are as follows:
(3-1) preparation of 0.25 g of protein powder, 1mL of gadolinium chloride (GdCl) having a concentration of 50mmol/L, respectively 3 ) 1mL of aqueous sodium hydroxide solution with concentration of 2 mol/L;
(3-2) dissolving protein powder in 9 ml deionized water at physiological temperature of 37deg.C, adding GdCl 3 Adding aqueous solution of sodium hydroxide after 5 minutes, continuously maintaining constant temperature and stirring at the speed of 700-800 revolutions per minute, and dialyzing for 24 hours by adopting a dialysis bag with molecular weight cutoff of 3500 and deionized water to obtain Gd-protein complex, so as to form third dispersion;
the step (4) of overall coating specifically comprises the following steps:
adding 2.5 ml of third dispersion liquid into 20 ml of second dispersion liquid, uniformly mixing, stirring for 6-12 hours at 15-25 ℃ in a dark place, centrifuging at 9000-11000 r/min after ultrasonic dispersion, taking solid to disperse in deionized water, and enabling Gd-protein complex to carry out integral coating on core-shell structure materials to form organic/inorganic hybrid nano biological materials, thus obtaining the gadolinium complex modified palladium-gold alloy diagnosis and treatment integrated nano composite system.
The palladium-gold alloy diagnosis and treatment integrated nano composite system is applied to preparing a material of a contrast agent for magnetic resonance imaging, CT imaging and photoacoustic imaging.
The palladium-gold alloy diagnosis and treatment integrated nano composite system is applied to preparing materials of a photo-thermal reagent and a thermodynamic treatment reagent for near infrared light excitation photo-thermal treatment.
The invention has the beneficial effects that:
(1) The invention overcomes the defects that the single diagnosis mode or treatment means in the prior art have limitations and the most effective tumor killing effect is difficult to achieve, and the provided gadolinium complex modified palladium-gold alloy diagnosis and treatment integrated nano composite system material is constructed by taking multi-mode imaging as guidance through unique component and microstructure design, is a multifunctional tumor diagnosis and treatment integrated nano material capable of combining multiple tumor treatment modes, has the characteristics of magnetic resonance imaging, CT imaging and photoacoustic imaging, and multi-mode treatment, namely the thermodynamic treatment and photo-thermal treatment of cancers, and provides a new strategy for the field of clinical multi-mode diagnosis and multi-mode treatment integration.
(2) According to the gadolinium complex modified palladium-gold alloy diagnosis and treatment integrated nano composite system and the preparation method thereof, the obtained nano composite system has the advantages of high thermal stability, good biocompatibility and the like, has high photo-thermal conversion efficiency, simultaneously has the functions of thermodynamic treatment and photo-thermal treatment, and realizes diagnosis and treatment integration in magnetic resonance imaging, photoacoustic imaging, CT imaging and other multimode imaging guided cancers.
(3) The preparation method of the gadolinium complex modified palladium-gold alloy diagnosis and treatment integrated nano composite system has the characteristics of mild and simple synthesis conditions, high repeatability and easiness in industrialization; the advantage of high repeatability of the nano composite system preparation is realized by using the mild and simple preparation conditions.
(4) The application of the gadolinium complex modified palladium-gold alloy diagnosis and treatment integrated nano composite system provided by the invention has the functions of magnetic resonance imaging, CT imaging, photoacoustic imaging and other multi-mode imaging, near infrared light photothermal treatment and thermodynamic treatment, realizes diagnosis and treatment integration, can realize accurate diagnosis in early cancer and is assisted by an efficient treatment means, has potential biomedical application prospect, and has great promotion significance for the progress of the cancer treatment field.
The present invention will be described in further detail with reference to the accompanying drawings and detailed description.
Drawings
FIG. 1 is a Transmission Electron Microscope (TEM) photograph of a gadolinium complex modified palladium-gold alloy diagnosis and treatment integrated nanocomposite system according to example 1 of the present invention;
FIG. 2 is a Fourier infrared spectrum of AIPH-PAPG, pdAb@PDA, AIPH and Gd-HSA in the preparation process of a gadolinium complex modified palladium-gold alloy diagnosis and treatment integrated nano-composite system in example 2 of the invention;
FIG. 3 is an in vitro thermal imaging photograph of the gadolinium complex modified palladium-gold alloy diagnosis and treatment integrated nanocomposite system of example 6 of the invention under 808nm laser excitation.
Detailed Description
The technical solutions of the present invention will be clearly and completely described below with reference to fig. 1 to 3 and examples.
Example 1
The palladium-gold alloy diagnosis and treatment integrated nanocomposite system material provided by the embodiment of the invention takes palladium-gold alloy nano particles as an inner core, dopamine monomers undergoing polymerization reaction form polydopamine shell layers coated on the outer surfaces of the palladium-gold alloy nano particles, then the polydopamine layers are used for loading medicine 2,2' -azobis [2- (2-imidazoline-2-yl) propane ] dihydrochloride, and then Gd-protein complexes are used for integrally coating the core-shell structure material after medicine loading to form an organic/inorganic hybrid nano biological material, namely a gadolinium complex modified palladium-gold alloy diagnosis and treatment integrated nanocomposite system. Wherein, the surface of the palladium-gold alloy nanoparticle is coated with a polydopamine layer, and the pi-pi interaction is utilized to load the medicine 2,2' -azobis [2- (2-imidazoline-2-yl) propane ] dihydrochloride; the Gd-protein complex is as follows: gd-bovine serum albumin complex (Gd-BSA).
The preparation method of the palladium-gold alloy diagnosis and treatment integrated nano composite system comprises the following steps:
(1) Preparing a first dispersion: preparing sodium citrate, aqueous solution of palladium chloride and aqueous solution of chloroauric acid, and surfactant Cetyl Trimethyl Ammonium Bromide (CTAB) and Cetyl Trimethyl Ammonium Chloride (CTAC) respectively, reducing the aqueous solution of palladium chloride and the aqueous solution of chloroauric acid by sodium citrate to synthesize palladium-gold alloy nano particles, and dispersing the palladium-gold alloy nano particles in deionized water; then adding dopamine monomer under alkaline condition, polymerizing to form polydopamine layer coated on the surface of palladium-gold alloy nano particle, ultrasonically dispersing, centrifuging, and dispersing solid in deionized water to form first dispersion; the method comprises the following specific steps:
(1-1) preparing an aqueous solution of palladium chloride and an aqueous solution of chloroauric acid, respectively;
(1-2) uniformly mixing 44 ml of cetyltrimethylammonium bromide (CTAB) and 5 ml of cetyltrimethylammonium chloride (CTAC) surfactant, adding 10mmol/L of aqueous solution of palladium chloride and 10mmol/L of 1.2 ml of mixed solution of aqueous solution of chloroauric acid (the mol ratio of the palladium chloride to the chloroauric acid is 1:1), adding 240 mu L of sodium citrate with the concentration of 100mmol/L after 20 minutes, and preserving the temperature for 16 hours at the constant temperature of 90 ℃ under the airtight condition to synthesize palladium-gold alloy nano particles;
(1-3) dispersing palladium-gold alloy nano particles in 20 ml of deionized water, then adding 5 mg of dopamine monomer salt, polymerizing dopamine monomer under alkaline condition with pH of 9, coating the surface of the palladium-gold alloy nano particles to form a polydopamine layer, centrifuging at a speed of 14000 rpm after ultrasonic dispersion, and dispersing the obtained solid in 20 ml of deionized water to form a first dispersion.
(2) Preparing a second dispersion: preparing 2,2' -azo-bis [2- (2-imidazolin-2-yl) propane ] dihydrochloride, and dissolving the 2,2' -azo-bis [2- (2-imidazolin-2-yl) propane ] dihydrochloride in a set amount of deionized water to obtain 2,2' -azo-bis [2- (2-imidazolin-2-yl) propane ] dihydrochloride aqueous solution; mixing the 2,2' -azobis [2- (2-imidazoline-2-yl) propane ] dihydrochloride aqueous solution with a first dispersion liquid, stirring in a dark place within a set time at room temperature, centrifuging after ultrasonic dispersion, and dispersing the solid in deionized water to form a second dispersion liquid; the method comprises the following specific steps:
(2-1) taking 0.2 g of 2,2 '-azobis [2- (2-imidazolin-2-yl) propane ] dihydrochloride, dissolving it in 5 ml of deionized water to obtain 2,2' -azobis [2- (2-imidazolin-2-yl) propane ] dihydrochloride aqueous solution;
(2-2) the aqueous solution of 2,2' -azobis [2- (2-imidazolin-2-yl) propane ] dihydrochloride was uniformly mixed with the first dispersion, stirred at room temperature for 12 hours in the dark, and after ultrasonic dispersion, centrifuged at 12000 rpm, and the solid was taken and dispersed in 20 ml deionized water to form a second dispersion.
(3) Preparing a third dispersion: respectively preparing protein powder and gadolinium chloride (GdCl) 3 ) An aqueous solution, an aqueous sodium hydroxide solution; dissolving protein powder in deionized water at constant temperature, adding GdCl 3 Adding sodium hydroxide aqueous solution into the aqueous solution, continuously maintaining constant temperature, rapidly stirring, dialyzing with dialysis bag and deionized water to obtain Gd-protein complex, and forming a third dispersion; the method comprises the following specific steps:
(3-1) preparation of 0.25 g of bovine serum albumin, 1mL of gadolinium chloride (GdCl) at a concentration of 50mmol/L, respectively 3 ) 1mL of aqueous sodium hydroxide solution with concentration of 2 mol/L;
(3-2) bovine serum albumin was dissolved in 9 ml of deionized water at physiological temperature of 37℃and GdCl was added 3 The aqueous solution was added after 5 minutes with aqueous sodium hydroxide solution and the constant temperature was maintained continuously at 700 revolutions per minuteStirring at a speed, dialyzing for 24 hours by using a dialysis bag with 3500 molecular weight cutoff and deionized water to obtain Gd-bovine serum albumin complex (Gd-BSA) to form a third dispersion;
(4) And (3) overall coating: mixing the second dispersion liquid and the third dispersion liquid according to a set proportion, stirring in a dark place at 15-25 ℃, performing ultrasonic dispersion after reaching a set time, centrifuging, taking the solid to disperse in deionized water, and enabling the Gd-protein complex to carry out integral coating on the core-shell structure material to form an organic/inorganic hybrid nano biological material, thereby obtaining the gadolinium complex modified palladium-gold alloy diagnosis and treatment integrated nano composite system material. The method comprises the following specific steps:
Adding 2.5 ml of a third dispersion liquid into 20 ml of a second dispersion liquid, uniformly mixing, stirring for 6 hours at 25 ℃ in a dark place, centrifuging at 10000 revolutions per minute after ultrasonic dispersion, taking solid to disperse in deionized water, and enabling Gd-bovine serum albumin (Gd-BSA) complex to carry out integral coating on a core-shell structure material to form an organic/inorganic hybrid nano biological material, thus obtaining the gadolinium complex modified palladium-gold alloy diagnosis and treatment integrated nano composite system.
Fig. 1 is a TEM photograph of a palladium-gold alloy diagnosis and treatment integrated nanocomposite system modified by gadolinium complex prepared in example 1 of the present invention, from which it can be observed that the palladium-gold alloy nanoparticle is coated with a polydopamine layer, 2' -azobis [2- (2-imidazolin-2-yl) propane ] dihydrochloride loaded with a drug, and finally a shell layer which is presented after being coated with Gd-bovine serum albumin complex (Gd-BSA), which shows that the preparation method can obtain a diagnosis and treatment integrated nanocomposite system with good morphology, uniform growth and high experimental repeatability, and the average diameter of the nanomaterial is about 90-100 nm, because the small-sized nanomaterial is easier to be endocytosed by cells, and is beneficial to in vivo circulation, which has important significance for use in biological imaging and treatment.
Example 2
The palladium-gold alloy diagnosis and treatment integrated nanocomposite system material provided by the embodiment is basically the same as the embodiment 1, and is characterized in that palladium-gold alloy nanoparticles are taken as an inner core, dopamine monomers undergoing polymerization reaction form a polydopamine shell layer coated on the outer surface of the palladium-gold alloy nanoparticles, then the polydopamine layer is loaded with medicine 2,2' -azobis [2- (2-imidazoline-2-yl) propane ] dihydrochloride, and then the loaded core-shell structure material is integrally coated by Gd-protein complex to form an organic/inorganic hybrid nano biological material, namely a gadolinium complex modified palladium-gold alloy diagnosis and treatment integrated nanocomposite system. Wherein, the surface of the palladium-gold alloy nanoparticle is coated with a polydopamine layer, and the pi-pi interaction is utilized to load the medicine 2,2' -azobis [2- (2-imidazoline-2-yl) propane ] dihydrochloride; the Gd-protein complex is as follows: gd-human serum albumin complex (Gd-HSA).
The preparation method of the palladium-gold alloy diagnosis and treatment integrated nano composite system comprises the following steps:
(1) Preparing a first dispersion: preparing sodium citrate, aqueous solution of palladium chloride and aqueous solution of chloroauric acid, and surfactant Cetyl Trimethyl Ammonium Bromide (CTAB) and Cetyl Trimethyl Ammonium Chloride (CTAC) respectively, reducing the aqueous solution of palladium chloride and the aqueous solution of chloroauric acid by sodium citrate to synthesize palladium-gold alloy nano particles, and dispersing the palladium-gold alloy nano particles in deionized water; then adding dopamine monomer under alkaline condition, polymerizing to form polydopamine layer coated on the surface of palladium-gold alloy nano particle, ultrasonically dispersing, centrifuging, and dispersing solid in deionized water to form first dispersion; the method comprises the following specific steps:
(1-1) preparing an aqueous solution of palladium chloride and an aqueous solution of chloroauric acid, respectively;
(1-2) uniformly mixing 44 ml of cetyltrimethylammonium bromide (CTAB) and 5 ml of cetyltrimethylammonium chloride (CTAC) surfactant, adding 10mmol/L of aqueous solution of palladium chloride and 10mmol/L of 1.2 ml of mixed solution of aqueous solution of chloroauric acid (the mol ratio of the palladium chloride to the chloroauric acid is 1:1), adding 240 mu L of sodium citrate with the concentration of 100mmol/L after 20 minutes, and preserving the temperature for 16 hours at the constant temperature of 90 ℃ under the airtight condition to synthesize palladium-gold alloy nano particles;
(1-3) dispersing palladium-gold alloy nano particles in 20 ml of deionized water, then adding 5 mg of dopamine monomer salt, polymerizing dopamine monomer under alkaline condition with pH of 9, coating the surface of the palladium-gold alloy nano particles to form a polydopamine layer, centrifuging at a speed of 14000 rpm after ultrasonic dispersion, and dispersing the obtained solid in 20 ml of deionized water to form a first dispersion liquid which is expressed as PdAU@PDA.
(2) Preparing a second dispersion: preparing 2,2' -azo-bis [2- (2-imidazolin-2-yl) propane ] dihydrochloride, and dissolving the 2,2' -azo-bis [2- (2-imidazolin-2-yl) propane ] dihydrochloride in a set amount of deionized water to obtain 2,2' -azo-bis [2- (2-imidazolin-2-yl) propane ] dihydrochloride aqueous solution; mixing the 2,2' -azobis [2- (2-imidazoline-2-yl) propane ] dihydrochloride aqueous solution with a first dispersion liquid, stirring in a dark place within a set time at room temperature, centrifuging after ultrasonic dispersion, and dispersing the solid in deionized water to form a second dispersion liquid; the method comprises the following specific steps:
(2-1) taking 0.2 g of 2,2 '-azobis [2- (2-imidazolin-2-yl) propane ] dihydrochloride (AIPH), dissolving it in 5 ml of deionized water to obtain 2,2' -azobis [2- (2-imidazolin-2-yl) propane ] dihydrochloride aqueous solution;
(2-2) the aqueous solution of 2,2' -azobis [2- (2-imidazolin-2-yl) propane ] dihydrochloride was uniformly mixed with the first dispersion, stirred at room temperature for 12 hours in the dark, and after ultrasonic dispersion, centrifuged at 12000 rpm, and the solid was taken and dispersed in 20 ml deionized water to form a second dispersion.
(3) Preparing a third dispersion: respectively preparing protein powder and gadolinium chloride (GdCl) 3 ) An aqueous solution, an aqueous sodium hydroxide solution; dissolving protein powder in deionized water at constant temperature, adding GdCl 3 Adding sodium hydroxide aqueous solution into the aqueous solution, continuously maintaining constant temperature, rapidly stirring, dialyzing with dialysis bag and deionized water to obtain Gd-protein complex, and forming a third dispersion; the method comprises the following specific steps:
(3-1) preparation of 0.25 g of human serum albumin, 1mL of gadolinium chloride (GdCl) at a concentration of 50mmol/L, respectively 3 ) 1mL of aqueous sodium hydroxide solution with concentration of 2 mol/L;
(3-2) dissolving human serum albumin in 9 ml deionized water at physiological temperature of 37 ℃, Adding GdCl 3 Adding sodium hydroxide aqueous solution after 5 minutes, continuously maintaining constant temperature and stirring at the speed of 700 revolutions per minute, and dialyzing for 24 hours by adopting a dialysis bag with molecular weight cutoff of 3500 and deionized water to obtain Gd-human serum albumin complex (Gd-HSA) to form a third dispersion;
(4) And (3) overall coating: mixing the second dispersion liquid and the third dispersion liquid according to a set proportion, stirring in a dark place at 15-25 ℃, performing ultrasonic dispersion after reaching a set time, centrifuging, taking the solid to disperse in deionized water, and enabling the Gd-protein complex to carry out integral coating on the core-shell structure material to form an organic/inorganic hybrid nano biological material, thereby obtaining the gadolinium complex modified palladium-gold alloy diagnosis and treatment integrated nano composite system material. The method comprises the following specific steps:
adding 2.5 ml of a third dispersion liquid into 20 ml of a second dispersion liquid, uniformly mixing, stirring for 6 hours at 25 ℃ in a dark place, centrifuging at 10000 revolutions per minute after ultrasonic dispersion, taking solid to disperse in deionized water, and integrally coating a core-shell structure material with Gd-human serum albumin complex (Gd-HSA) to form an organic/inorganic hybrid nano biological material, thus obtaining a gadolinium complex modified palladium-gold alloy diagnosis and treatment integrated nano composite system, which is expressed as AIPH-PAPG.
FIG. 2 is a Fourier infrared spectrum of AIPH-PAPG, pdAb@PDA, AIPH and Gd-HSA in the preparation process of a gadolinium complex modified palladium-gold alloy diagnosis and treatment integrated nanocomposite system provided in example 2 of the invention, and a wave number of 1350cm is shown from the spectrum -1 Can be attributed to the absorption peak of 2,2' -azobis [2- (2-imidazolin-2-yl) propane ]]-CH of dihydrochloride (AIPH) 3 Bending vibration with wave number of 1596cm -1 Is attributed to the absorption peak of 2,2' -azobis [2- (2-imidazolin-2-yl) propane ]]N-H flexural vibration of dihydrochloride (AIPH) and Gd-human serum albumin complex (Gd-HSA) with wave number of 1395cm -1 The absorption peaks of the catalyst are attributed to-OH bending vibration of Gd-human serum albumin complex (Gd-HSA), and the accurate attribution of the peak positions can prove the successful preparation of the gadolinium complex modified palladium-gold alloy diagnosis and treatment integrated nano composite system, which benefits from the simple preparation method conditionsSingle, mild and easy to control, thereby leading the preparation repeatability of the nano composite system to be high.
Example 3
The palladium-gold alloy diagnosis and treatment integrated nanocomposite system material provided by the embodiment is basically the same as that of the embodiment 1 and 2, and is characterized in that palladium-gold alloy nano particles are taken as inner cores, dopamine monomers undergoing polymerization reaction form polydopamine shell layers coated on the outer surfaces of the palladium-gold alloy nano particles, then the polydopamine layers are loaded with medicine 2,2' -azobis [2- (2-imidazoline-2-yl) propane ] dihydrochloride, and then Gd-protein complexes are used for integrally coating the core-shell structural material after medicine loading, so that an organic/inorganic hybrid nano biological material, namely a gadolinium complex modified palladium-gold alloy diagnosis and treatment integrated nanocomposite system is formed. Wherein, the surface of the palladium-gold alloy nanoparticle is coated with a polydopamine layer, and the pi-pi interaction is utilized to load the medicine 2,2' -azobis [2- (2-imidazoline-2-yl) propane ] dihydrochloride; the Gd-protein complex is as follows: gd-bovine serum albumin complex (Gd-BSA).
The preparation method of the palladium-gold alloy diagnosis and treatment integrated nano composite system comprises the following steps:
(1) Preparing a first dispersion: preparing sodium citrate, aqueous solution of palladium chloride and aqueous solution of chloroauric acid, and surfactant Cetyl Trimethyl Ammonium Bromide (CTAB) and Cetyl Trimethyl Ammonium Chloride (CTAC) respectively, reducing the aqueous solution of palladium chloride and the aqueous solution of chloroauric acid by sodium citrate to synthesize palladium-gold alloy nano particles, and dispersing the palladium-gold alloy nano particles in deionized water; then adding dopamine monomer under alkaline condition, polymerizing to form polydopamine layer coated on the surface of palladium-gold alloy nano particle, ultrasonically dispersing, centrifuging, and dispersing solid in deionized water to form first dispersion; the method comprises the following specific steps:
(1-1) preparing an aqueous solution of palladium chloride and an aqueous solution of chloroauric acid, respectively;
(1-2) uniformly mixing 44 ml of cetyltrimethylammonium bromide (CTAB) and 5 ml of cetyltrimethylammonium chloride (CTAC) surfactant, adding 10mmol/L of aqueous solution of palladium chloride and 1.2 ml of mixed solution of 10mmol/L of aqueous solution of chloroauric acid (the mol ratio of the palladium chloride to the chloroauric acid is 1:2), adding 240 mu L of sodium citrate with the concentration of 100mmol/L after 20 minutes, and preserving the temperature for 20 hours at the constant temperature of 90 ℃ under the airtight condition to synthesize palladium-gold alloy nano particles;
(1-3) dispersing palladium-gold alloy nano particles in 20 ml of deionized water, then adding 5 mg of dopamine monomer salt, polymerizing dopamine monomer under alkaline condition with pH of 12, coating the surface of the palladium-gold alloy nano particles to form a polydopamine layer, centrifuging at a speed of 14000 rpm after ultrasonic dispersion, and dispersing the obtained solid in 20 ml of deionized water to form a first dispersion.
(2) Preparing a second dispersion: preparing 2,2' -azo-bis [2- (2-imidazolin-2-yl) propane ] dihydrochloride, and dissolving the 2,2' -azo-bis [2- (2-imidazolin-2-yl) propane ] dihydrochloride in a set amount of deionized water to obtain 2,2' -azo-bis [2- (2-imidazolin-2-yl) propane ] dihydrochloride aqueous solution; mixing the 2,2' -azobis [2- (2-imidazoline-2-yl) propane ] dihydrochloride aqueous solution with a first dispersion liquid, stirring in a dark place within a set time at room temperature, centrifuging after ultrasonic dispersion, and dispersing the solid in deionized water to form a second dispersion liquid; the method comprises the following specific steps:
(2-1) taking 0.2 g of 2,2 '-azobis [2- (2-imidazolin-2-yl) propane ] dihydrochloride, dissolving it in 5 ml of deionized water to obtain 2,2' -azobis [2- (2-imidazolin-2-yl) propane ] dihydrochloride aqueous solution;
(2-2) the aqueous solution of 2,2' -azobis [2- (2-imidazolin-2-yl) propane ] dihydrochloride was uniformly mixed with the first dispersion, stirred at room temperature for 15 hours in the dark, and after ultrasonic dispersion, centrifuged at 12000 rpm, and the solid was taken and dispersed in 20 ml deionized water to form a second dispersion.
(3) Preparing a third dispersion: respectively preparing protein powder and gadolinium chloride (GdCl) 3 ) An aqueous solution, an aqueous sodium hydroxide solution; dissolving protein powder in deionized water at constant temperature, adding GdCl 3 Adding sodium hydroxide aqueous solution into the aqueous solution, continuously maintaining constant temperature, rapidly stirring, dialyzing with dialysis bag and deionized water to obtain Gd-protein preparationA compound forming a third dispersion; the method comprises the following specific steps:
(3-1) preparation of 0.25 g of bovine serum albumin, 1mL of gadolinium chloride (GdCl) at a concentration of 50mmol/L, respectively 3 ) 1mL of aqueous sodium hydroxide solution with concentration of 2 mol/L;
(3-2) bovine serum albumin was dissolved in 9 ml of deionized water at physiological temperature of 37℃and GdCl was added 3 Adding sodium hydroxide aqueous solution after 5 minutes, continuously maintaining constant temperature and stirring at a speed of 800 revolutions per minute, and dialyzing for 24 hours by using a dialysis bag with molecular weight cutoff of 3500 and deionized water to obtain Gd-bovine serum albumin complex (Gd-BSA) to form a third dispersion;
(4) And (3) overall coating: mixing the second dispersion liquid and the third dispersion liquid according to a set proportion, stirring in a dark place at 15-25 ℃, performing ultrasonic dispersion after reaching a set time, centrifuging, taking the solid to disperse in deionized water, and enabling the Gd-protein complex to carry out integral coating on the core-shell structure material to form an organic/inorganic hybrid nano biological material, thereby obtaining the gadolinium complex modified palladium-gold alloy diagnosis and treatment integrated nano composite system material. The method comprises the following specific steps:
Adding 2.5 ml of a third dispersion liquid into 20 ml of a second dispersion liquid, uniformly mixing, stirring for 10 hours at 25 ℃ in a dark place, centrifuging at 10000 revolutions per minute after ultrasonic dispersion, taking solid to disperse in deionized water, and enabling Gd-bovine serum albumin (Gd-BSA) complex to carry out integral coating on a core-shell structure material to form an organic/inorganic hybrid nano biological material, thus obtaining the gadolinium complex modified palladium-gold alloy diagnosis and treatment integrated nano composite system.
Example 4
The palladium-gold alloy diagnosis and treatment integrated nanocomposite system material provided by the embodiment is basically the same as that of the embodiment 1-3, and is characterized in that palladium-gold alloy nanoparticles are taken as an inner core, dopamine monomers undergoing polymerization reaction form polydopamine shell layers coated on the outer surfaces of the palladium-gold alloy nanoparticles, then the polydopamine layers are loaded with medicine 2,2' -azobis [2- (2-imidazoline-2-yl) propane ] dihydrochloride, and then Gd-protein complexes are used for integrally coating the loaded core-shell structural material to form an organic/inorganic hybrid nano biological material, namely a gadolinium complex modified palladium-gold alloy diagnosis and treatment integrated nanocomposite system. Wherein, the surface of the palladium-gold alloy nanoparticle is coated with a polydopamine layer, and the pi-pi interaction is utilized to load the medicine 2,2' -azobis [2- (2-imidazoline-2-yl) propane ] dihydrochloride; the Gd-protein complex is as follows: gd-human serum albumin complex (Gd-HSA).
The preparation method of the palladium-gold alloy diagnosis and treatment integrated nano composite system comprises the following steps:
(1) Preparing a first dispersion: preparing sodium citrate, aqueous solution of palladium chloride and aqueous solution of chloroauric acid, and surfactant Cetyl Trimethyl Ammonium Bromide (CTAB) and Cetyl Trimethyl Ammonium Chloride (CTAC) respectively, reducing the aqueous solution of palladium chloride and the aqueous solution of chloroauric acid by sodium citrate to synthesize palladium-gold alloy nano particles, and dispersing the palladium-gold alloy nano particles in deionized water; then adding dopamine monomer under alkaline condition, polymerizing to form polydopamine layer coated on the surface of palladium-gold alloy nano particle, ultrasonically dispersing, centrifuging, and dispersing solid in deionized water to form first dispersion; the method comprises the following specific steps:
(1-1) preparing an aqueous solution of palladium chloride and an aqueous solution of chloroauric acid, respectively;
(1-2) uniformly mixing 44 ml of cetyltrimethylammonium bromide (CTAB) and 5 ml of cetyltrimethylammonium chloride (CTAC) surfactant, adding 10mmol/L of aqueous solution of palladium chloride and 1.2 ml of mixed solution of 10mmol/L of aqueous solution of chloroauric acid (the mol ratio of the palladium chloride to the chloroauric acid is 1:2), adding 240 mu L of sodium citrate with the concentration of 100mmol/L after 20 minutes, and preserving the temperature for 20 hours at the constant temperature of 90 ℃ under the airtight condition to synthesize palladium-gold alloy nano particles;
(1-3) dispersing palladium-gold alloy nano particles in 20 ml of deionized water, then adding 5 mg of dopamine monomer salt, polymerizing dopamine monomer under alkaline condition with pH of 12, coating the surface of the palladium-gold alloy nano particles to form a polydopamine layer, centrifuging at a speed of 14000 rpm after ultrasonic dispersion, and dispersing the obtained solid in 20 ml of deionized water to form a first dispersion.
(2) Preparing a second dispersion: preparing 2,2' -azo-bis [2- (2-imidazolin-2-yl) propane ] dihydrochloride, and dissolving the 2,2' -azo-bis [2- (2-imidazolin-2-yl) propane ] dihydrochloride in a set amount of deionized water to obtain 2,2' -azo-bis [2- (2-imidazolin-2-yl) propane ] dihydrochloride aqueous solution; mixing the 2,2' -azobis [2- (2-imidazoline-2-yl) propane ] dihydrochloride aqueous solution with a first dispersion liquid, stirring in a dark place within a set time at room temperature, centrifuging after ultrasonic dispersion, and dispersing the solid in deionized water to form a second dispersion liquid; the method comprises the following specific steps:
(2-1) taking 0.2 g of 2,2 '-azobis [2- (2-imidazolin-2-yl) propane ] dihydrochloride, dissolving it in 5 ml of deionized water to obtain 2,2' -azobis [2- (2-imidazolin-2-yl) propane ] dihydrochloride aqueous solution;
(2-2) the aqueous solution of 2,2' -azobis [2- (2-imidazolin-2-yl) propane ] dihydrochloride was uniformly mixed with the first dispersion, stirred at room temperature for 15 hours in the dark, and after ultrasonic dispersion, centrifuged at 12000 rpm, and the solid was taken and dispersed in 20 ml deionized water to form a second dispersion.
(3) Preparing a third dispersion: respectively preparing protein powder and gadolinium chloride (GdCl) 3 ) An aqueous solution, an aqueous sodium hydroxide solution; dissolving protein powder in deionized water at constant temperature, adding GdCl 3 Adding sodium hydroxide aqueous solution into the aqueous solution, continuously maintaining constant temperature, rapidly stirring, dialyzing with dialysis bag and deionized water to obtain Gd-protein complex, and forming a third dispersion; the method comprises the following specific steps:
(3-1) preparation of 0.25 g of human serum albumin, 1mL of gadolinium chloride (GdCl) at a concentration of 50mmol/L, respectively 3 ) 1mL of aqueous sodium hydroxide solution with concentration of 2 mol/L;
(3-2) dissolving human serum albumin in 9 ml deionized water at physiological temperature of 37deg.C, adding GdCl 3 Adding sodium hydroxide aqueous solution after 5 min, continuously maintaining constant temperature and stirring at 800 rpm, and dialyzing with dialysis bag with molecular weight cut-off of 3500 and deionized water for 24 hr to obtain Gd-human serum protein complex (G)d-HSA) to form a third dispersion;
(4) And (3) overall coating: mixing the second dispersion liquid and the third dispersion liquid according to a set proportion, stirring in a dark place at 15-25 ℃, performing ultrasonic dispersion after reaching a set time, centrifuging, taking the solid to disperse in deionized water, and enabling the Gd-protein complex to carry out integral coating on the core-shell structure material to form an organic/inorganic hybrid nano biological material, thereby obtaining the gadolinium complex modified palladium-gold alloy diagnosis and treatment integrated nano composite system material. The method comprises the following specific steps:
Adding 2.5 ml of a third dispersion liquid into 20 ml of a second dispersion liquid, uniformly mixing, stirring for 10 hours at 25 ℃ in a dark place, centrifuging at 10000 revolutions per minute after ultrasonic dispersion, taking solid to disperse in deionized water, and integrally coating a core-shell structure material with Gd-human serum albumin complex (Gd-HSA) to form an organic/inorganic hybrid nano biological material, thus obtaining the gadolinium complex modified palladium-gold alloy diagnosis and treatment integrated nano composite system.
Example 5
The application of the palladium-gold alloy diagnosis and treatment integrated nano composite system provided by the embodiment is that the palladium-gold alloy diagnosis and treatment integrated nano composite system is used as a material for preparing contrast agents of magnetic resonance imaging, CT imaging and photoacoustic imaging, is a diagnosis and treatment integrated new material integrating multi-mode imaging and dual-mode treatment, and provides a new strategy for the field of clinical multi-mode diagnosis and multi-mode treatment integration.
Example 6
The palladium-gold alloy diagnosis and treatment integrated nano composite system provided by the embodiment is a diagnosis and treatment integrated nano composite system material prepared by the embodiment 1, is used for preparing a material of a photo-thermal reagent and a thermodynamic treatment reagent for near infrared light excitation photo-thermal treatment, integrates multi-mode imaging and dual-mode treatment, and can be widely applied to in-vitro photo-thermal imaging.
The gadolinium complex modified palladium-gold alloy diagnosis and treatment integrated nanocomposite system material prepared in the embodiment is used for in-vitro photothermal imaging under 808nm laser excitation, and comprises the following steps:
(1) Preparing a gadolinium complex modified palladium-gold alloy diagnosis and treatment integrated nano composite system, a quartz cuvette, a continuously excited 808nm laser and a thermal imaging camera in the embodiment 1;
(2) The nanocomposite system of example 1 was prepared with deionized water into solutions of 0. Mu.g/mL, 50. Mu.g/mL, 100. Mu.g/mL, 200. Mu.g/mL, and 400. Mu.g/mL, and sonicated to uniformity, forming a fourth dispersion;
(3) Adding 2mL of the fourth dispersion liquid with different concentrations into a quartz cuvette, fixing on an iron stand, and using 1.5W/cm 2 Continuously irradiating the fourth dispersion with a 808nm laser while recording real-time temperatures and thermal imaging photographs of the fourth dispersion at different times with a thermal imaging camera.
FIG. 3 is a photograph of an integrated palladium-gold alloy diagnosis and treatment nanocomposite obtained in example 1 of the present invention for in vitro photothermal imaging, wherein the temperature gradually increases with increasing concentration of the fourth dispersion under 808nm laser excitation; at the same time the temperature of the dispersion also increased with the delay of the irradiation time, after 8 minutes the temperature of the solution had tended to stabilize, up to 60 ℃. The related literature reports that excellent photo-thermal treatment and cancer cell killing effects can be achieved by culturing tumor cells for 1 hour at 42 ℃, and the characterization shows that the nano-composite system provided by the invention has great application prospects in the photo-thermal treatment of tumor cells.
According to the preparation method of the gadolinium complex modified palladium-gold alloy diagnosis and treatment integrated nano composite system, firstly, sodium citrate is used for reducing chloropalladate and chloroauric acid in the presence of a surfactant to obtain palladium-gold alloy nano particles; then, the dopamine monomer is polymerized under alkaline condition to coat a polydopamine layer on the surface of the palladium-gold alloy nano particle, and the drug 2,2' -azobis [2- (2-imidazoline-2-yl) propane ] dihydrochloride is loaded on the surface of the palladium-gold alloy nano particle through pi-pi interaction generated by pi electron cloud with rich polydopamine layer structure; and finally, coating the material by using a prepared Gd-protein complex to obtain the gadolinium complex modified palladium-gold alloy diagnosis and treatment integrated nano composite system.
The above description is only of the preferred embodiment of the present invention and is not intended to limit the present invention in any way. Any person skilled in the art may make many possible variations or modifications of the technical solution of the present invention using the method and technical content disclosed above without departing from the scope of the technical solution of the present invention as equivalent embodiments. Therefore, all equivalent modifications made according to the structure, construction and principle of the present invention are intended to be included within the scope of the present invention.
Claims (7)
1. The palladium-gold alloy diagnosis and treatment integrated nanocomposite system is characterized in that palladium-gold alloy nanoparticles are taken as an inner core, dopamine monomers undergoing polymerization reaction form a polydopamine shell layer coated on the outer surface of the palladium-gold alloy nanoparticles, then the polydopamine layer is loaded with a drug 2,2' -azobis [2- (2-imidazoline-2-yl) propane ] dihydrochloride, and then a Gd-protein complex is used for integrally coating a core-shell structural material after drug loading to form an organic/inorganic hybrid nano biological material, namely the gadolinium complex modified palladium-gold alloy diagnosis and treatment integrated nanocomposite system;
the surface of the palladium-gold alloy nanoparticle is coated with a polydopamine layer, and the pi-pi interaction is utilized to load medicine 2,2' -azobis [2- (2-imidazolin-2-yl) propane ] dihydrochloride;
the Gd-protein complex is as follows: one of Gd-bovine serum albumin complex Gd-BSA and Gd-human serum albumin complex Gd-HSA;
the gadolinium complex modified palladium-gold alloy diagnosis and treatment integrated nano composite system is prepared by the following steps:
(1) Preparing a first dispersion: preparing sodium citrate, aqueous solution of palladium chloride and aqueous solution of chloroauric acid, and surfactant Cetyl Trimethyl Ammonium Bromide (CTAB) and Cetyl Trimethyl Ammonium Chloride (CTAC) respectively, reducing the aqueous solution of palladium chloride and the aqueous solution of chloroauric acid by sodium citrate to synthesize palladium-gold alloy nano particles, and dispersing the palladium-gold alloy nano particles in deionized water; then adding dopamine monomer under alkaline condition, polymerizing to form polydopamine layer coated on the surface of palladium-gold alloy nano particle, ultrasonically dispersing, centrifuging, and dispersing solid in deionized water to form first dispersion;
(2) Preparing a second dispersion: preparing 2,2' -azo-bis [2- (2-imidazolin-2-yl) propane ] dihydrochloride, and dissolving the 2,2' -azo-bis [2- (2-imidazolin-2-yl) propane ] dihydrochloride in a set amount of deionized water to obtain 2,2' -azo-bis [2- (2-imidazolin-2-yl) propane ] dihydrochloride aqueous solution; mixing the 2,2' -azobis [2- (2-imidazoline-2-yl) propane ] dihydrochloride aqueous solution with a first dispersion liquid, stirring in a dark place within a set time at room temperature, centrifuging after ultrasonic dispersion, and dispersing the solid in deionized water to form a second dispersion liquid;
(3) Preparing a third dispersion: respectively preparing protein powder and gadolinium chloride GdCl 3 An aqueous solution, an aqueous sodium hydroxide solution; dissolving protein powder in deionized water at constant temperature, adding GdCl 3 Adding sodium hydroxide aqueous solution into the aqueous solution, continuously maintaining constant temperature, rapidly stirring, dialyzing with dialysis bag and deionized water to obtain Gd-protein complex, and forming a third dispersion;
(4) And (3) overall coating: mixing the second dispersion liquid and the third dispersion liquid according to a set proportion, stirring in a dark place at 15-25 ℃, performing ultrasonic dispersion after reaching a set time, centrifuging, taking the solid to disperse in deionized water, and enabling the Gd-protein complex to carry out integral coating on the core-shell structure material to form an organic/inorganic hybrid nano biological material, thereby obtaining the gadolinium complex modified palladium-gold alloy diagnosis and treatment integrated nano composite system material.
2. The gadolinium complex modified palladium-gold alloy diagnosis and treatment integrated nanocomposite system according to claim 1, wherein the specific steps of preparing the first dispersion liquid in step (1) are as follows:
(1-1) preparing an aqueous solution of palladium chloride and an aqueous solution of chloroauric acid, respectively;
(1-2) uniformly mixing 44 ml of Cetyl Trimethyl Ammonium Bromide (CTAB) and 5 ml of Cetyl Trimethyl Ammonium Chloride (CTAC) surfactant, and adding 1.2 ml of mixed solution of 10 mmol/L aqueous solution of palladium chloride acid and 10 mmol/L aqueous solution of chloroauric acid, wherein the mol ratio of the palladium chloride acid to the chloroauric acid is 1:1-1:2; adding 200-250 mu L of sodium citrate with the concentration of 100 mmol/L after 20 minutes, and preserving heat for 16-20 hours at a constant temperature of 80-100 ℃ under a closed condition to synthesize palladium-gold alloy nano particles;
(1-3) dispersing palladium-gold alloy nano particles in 20 ml of deionized water, then adding 5 mg of dopamine monomer salt, polymerizing the dopamine monomer under an alkaline condition with the pH value of 9-12, coating the surface of the palladium-gold alloy nano particles to form a polydopamine layer, centrifuging at a speed of 13000-15000 rpm after ultrasonic dispersion, and dispersing the obtained solid in 20 ml of deionized water to form a first dispersion liquid.
3. The gadolinium complex modified palladium-gold alloy diagnosis and treatment integrated nanocomposite system according to claim 1, wherein the specific steps of preparing the second dispersion liquid in the step (2) are as follows:
(2-1) taking 0.1-0.2 g of 2,2' -azobis [2- (2-imidazolin-2-yl) propane ] dihydrochloride, and dissolving the 2,2' -azobis [2- (2-imidazolin-2-yl) propane ] dihydrochloride in 5 ml of deionized water to obtain 2,2' -azobis [2- (2-imidazolin-2-yl) propane ] dihydrochloride aqueous solution;
(2-2) uniformly mixing the 2,2' -azobis [2- (2-imidazoline-2-yl) propane ] dihydrochloride aqueous solution with the first dispersion liquid, stirring for 10-15 hours at room temperature in a dark place, centrifuging at a speed of 11000-13000 rpm after ultrasonic dispersion, and dispersing the solid in 20 milliliters of deionized water to form a second dispersion liquid.
4. The gadolinium complex modified palladium-gold alloy diagnosis and treatment integrated nanocomposite system according to claim 1, wherein the specific steps for preparing the third dispersion liquid in the step (3) are as follows:
(3-1) preparation of 0.25 g of protein powder, 1 mL g/L gadolinium chloride GdCl 3 An aqueous solution, 1 mL concentration of 2 mol/L sodium hydroxide aqueous solution;
(3-2) dissolving protein powder in 9 ml deionized water at physiological temperature of 37deg.C, adding GdCl 3 And (3) adding the aqueous solution into the aqueous solution after 5 minutes, continuously maintaining the constant temperature and stirring at the speed of 700-800 revolutions per minute, and dialyzing for 24 hours by using a dialysis bag with the molecular weight cutoff of 3500 and deionized water to obtain the Gd-protein complex, thereby forming a third dispersion.
5. The gadolinium complex modified palladium-gold alloy diagnosis and treatment integrated nanocomposite system according to claim 1, wherein the step of integrally coating in the step (4) is specifically:
adding 2.5 ml of a third dispersion liquid into 20 ml of a second dispersion liquid, uniformly mixing, stirring for 6-12 hours at 15-25 ℃ in a dark place, performing ultrasonic dispersion, centrifuging at 9000-11000 r/min, taking the solid to disperse in deionized water, and integrally coating a core-shell structure material by using Gd-protein complex to form an organic/inorganic hybrid nano biological material, thus obtaining the gadolinium complex modified palladium-gold alloy diagnosis and treatment integrated nano composite system.
6. The application of the gadolinium complex modified palladium-gold alloy diagnosis and treatment integrated nano composite system as a preparation material in preparing contrast agents for magnetic resonance imaging, CT imaging and photoacoustic imaging.
7. The application of the gadolinium complex modified palladium-gold alloy diagnosis and treatment integrated nano composite system as a preparation material in preparing a photo-thermal reagent and a thermodynamic treatment reagent for near infrared light excitation luminescence thermal treatment according to claim 1.
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