CN109966490B - Degradable antimony nanostructure, preparation method and application - Google Patents
Degradable antimony nanostructure, preparation method and application Download PDFInfo
- Publication number
- CN109966490B CN109966490B CN201910221673.2A CN201910221673A CN109966490B CN 109966490 B CN109966490 B CN 109966490B CN 201910221673 A CN201910221673 A CN 201910221673A CN 109966490 B CN109966490 B CN 109966490B
- Authority
- CN
- China
- Prior art keywords
- antimony
- degradable
- dispersion
- nano
- nanostructure
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
- A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
- A61K31/704—Compounds 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- 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
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
- A61K9/143—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with inorganic compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Inorganic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Molecular Biology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention discloses a degradable antimony nano-structure, which is characterized in that anticancer drug adriamycin hydrochloride is loaded on the surface of degradable antimony nano-particles; the antimony nano particles have electronegativity, perform electrostatic interaction with doxorubicin hydrochloride with positive charge, and have good water solubility after the surface of the formed nano structure is further modified by an organic ligand; and the whole nanostructure can be degraded under the set laser radiation. The invention also discloses a preparation method of the structure, which adopts a direct reduction method to load the nano particles with adriamycin hydrochloride anticancer drugs. It can be used for chemotherapy and photothermal therapy. The nano structure provided by the invention has the advantages of uniform appearance, uniform size, good biocompatibility, high drug loading rate and photo-thermal conversion efficiency, and degradable property. The nanostructure can be used as preparation, and can be widely applied to chemotherapy and photothermal physiotherapy, and the synergistic effect can greatly improve the treatment efficiency.
Description
Technical Field
The invention relates to the technical field of biological nano materials, in particular to a degradable antimony nano structure for synergistic chemotherapy and photothermal physiotherapy, a preparation method and application.
Background
Nowadays, the physical health is more and more concerned, however, cancer still remains one of the important causes of human death. At present, pharmacotherapy and radiotherapy are the most important treatment methods for treating cancers, the former treatment method generates drug resistance in long-term treatment, and the latter treatment method has great side effect on the body due to radioactive radiation, which greatly limits the treatment effect of the drugs and the radiotherapy. The photothermal therapy is a cancer therapy method in which a material having a high photothermal conversion efficiency is introduced into a tumor tissue in an active targeting or passive targeting manner, and then light is converted into heat by irradiation of an external light source, thereby killing cancer cells by increasing the temperature. At present, various types of photothermal conversion biological nano materials are widely applied to photothermal physiotherapy.
However, the therapeutic effect of the single photothermal therapy is still not satisfactory, and therefore, researchers have tried to combine photothermal therapy with various therapeutic methods (e.g., chemotherapy, photodynamic therapy, radiotherapy, etc.) to improve the therapeutic effect. Among them, chemotherapy is receiving much attention as the most effective and wide cancer treatment method at present, and studies have shown that the treatment efficacy can be effectively enhanced by using a single nanostructure for the synergistic chemotherapy and the photothermal therapy, compared to the photothermal therapy or the chemotherapy alone. In addition, the biological toxicity of the nano-materials is also the focus of research of scientists. The longer the time that the nano material stays in the blood, the more toxic it is to the biological tissue, but at the same time, it is required to keep the blood circulation time long enough to ensure the treatment effect, so the development of biodegradable high-efficiency nano material has also attracted great attention.
At present, the development of degradable nano materials for synergistic treatment has a good application prospect, can effectively improve the treatment effect, can greatly reduce the toxicity brought by biological materials, and becomes a hotspot and a focus of research of people.
However, the synergetic chemical and photothermal physiotherapy nanostructure prepared by the existing process method has the defects of complex and unstable structure, poor water solubility and biocompatibility, incapability of degradation and the like, so that the application of the nanostructure is limited; in addition, the conventional preparation method has complex process and high raw material and equipment price, and is not easy to realize stable mass production.
Disclosure of Invention
Aiming at the defects of the prior art, the invention provides the degradable antimony nanostructure which has stable structure, good water solubility and biocompatibility, high photothermal conversion efficiency and high drug loading rate, so as to overcome the defects of the existing product, meet the requirements of clinical cooperative treatment on diseases such as cancer and the like, improve the treatment effect and expand the application field.
The invention also provides a method for preparing the degradable antimony nanostructure, which adopts a direct reduction method to overcome the problems of complex process, high raw material and equipment price and difficult realization of stable mass production of the conventional preparation method.
The invention also provides application of the degradable antimony nanostructure as a diagnosis and treatment preparation in the field of biological medicine.
In order to achieve the purpose, the invention adopts the technical scheme that:
a degradable antimony nano-structure is characterized in that the nano-structure is formed by loading an anticancer drug adriamycin hydrochloride on the surface of degradable antimony nano-particles; the antimony nano particles have electronegativity, perform electrostatic interaction with doxorubicin hydrochloride with positive charge, and have good water solubility after the surface of the formed nano structure is further modified by an organic ligand; and the whole nanostructure can be degraded under the set laser radiation.
The preparation method of the degradable antimony nanostructure is characterized by comprising the following steps of:
1) dissolving sodium borohydride serving as a reducing agent in N-methyl-2-pyrrolidone (NMP), ultrasonically dispersing, placing in an oil bath, and stirring for dispersing to obtain a first dispersion liquid;
2) dissolving antimony chloride in N-methyl-2-pyrrolidone, adding into the first dispersion, continuously stirring, and obtaining antimony nanoparticles after crystal growth to obtain a second dispersion;
3) mixing the obtained second dispersion with doxorubicin hydrochloride (DOX) anticancer drug, and continuously stirring to obtain an antimony nanostructure loaded by doxorubicin hydrochloride, so as to obtain a third dispersion;
4) and fully stirring and mixing the water-soluble surface organic ligand and the third dispersion liquid to obtain the degradable antimony nano structure for the cooperative chemotherapy and photo-thermal physiotherapy, wherein the degradable antimony nano structure is formed by loading adriamycin hydrochloride anticancer drugs on the surfaces of antimony nano particles.
The first dispersion liquid in the step 1) comprises the following specific steps: dissolving 280-300mg sodium borohydride in 25mL of N-methyl-2-pyrrolidone, ultrasonically dispersing for 30min, placing the mixture in an oil bath pot, and continuously stirring until the temperature is raised to 60 ℃ to obtain a first dispersion liquid.
The second dispersion liquid in the step 2) comprises the following specific steps: firstly, dissolving 3.5-4.0g of antimony chloride in 5mL of N-methyl-2-pyrrolidone by ultrasonic, then quickly adding the antimony chloride into the first dispersion liquid, uniformly mixing, continuously stirring for 2h, centrifugally washing, and re-dispersing in 10mL of deionized water to obtain a second dispersion liquid.
The specific steps of the step 3) are as follows: dissolving 8-8.1mg of DOX in 4mL of deionized water, uniformly mixing with the second dispersion, stirring overnight in the dark, centrifugally washing, and re-dispersing in ultrapure water to obtain a third dispersion.
The specific steps of the step 4) are as follows: dissolving 50-60mg of polyacrylic acid (PAA) as a surface organic ligand in 10mL of deionized water, carrying out ultrasonic dispersion, fully stirring and mixing with the third dispersion, and carrying out centrifugal washing to obtain the degradable antimony nanostructure for synergistic chemotherapy and photothermal physiotherapy.
The water-soluble surface organic ligand in the step 4) comprises: polyvinylpyrrolidone (PVP), polyethylene glycol (PEG), polyacrylic acid (PAA), Polyethyleneimine (PEI).
The degradable antimony nanostructure is characterized in that the degradable antimony nanostructure is used as a diagnosis and treatment preparation and applied to cooperative chemotherapy and photothermal physiotherapy.
The invention has the beneficial effects that:
(1) according to the preparation method of the degradable antimony nanostructure for synergistic chemotherapy and photothermal physiotherapy, the key components and the proportion are controlled, so that the degradable antimony nanostructure provided by the invention is uniform in appearance, uniform in size, good in biocompatibility, high in drug loading rate and photothermal conversion efficiency, and integrally degradable. The nano structure is used as a preparation for the synergistic effect of chemotherapy and photothermal physiotherapy, so that the treatment efficiency is greatly improved.
(2) According to the preparation method of the degradable antimony nanostructure, a direct reduction method is adopted, the reducibility of sodium borohydride is utilized, antimony nanoparticles are obtained through reduction, and the degradable antimony nanostructure for synergistic chemotherapy and photothermal physiotherapy is obtained after the doxorubicin hydrochloride drug is loaded. The preparation method effectively overcomes the defects of the existing method, and has the advantages of simple preparation process, simple process, mild reaction conditions, easy process control, good repeatability, simple equipment and low cost, and the obtained nano-structure has uniform appearance, uniform size and good biocompatibility; and has high drug loading rate and photo-thermal conversion efficiency, stable yield and quality, and easy industrialization.
(3) The degradable antimony nanostructure and the preparation method thereof provided by the invention are characterized in that antimony chloride is directly reduced by utilizing the strong reducibility of sodium borohydride to obtain antimony nanoparticles which have good laser radiation degradability, and after doxorubicin hydrochloride is loaded, the nanostructure with chemical and photo-thermal physical therapy functions is obtained, so that the treatment effect is effectively improved, and the application range of the nanostructure is expanded.
(4) When the degradable antimony nanostructure provided by the invention is used as a diagnosis and treatment preparation for synergistic chemotherapy and photothermal physiotherapy, the photothermal conversion efficiency can reach 40-50%, and the drug loading rate can reach 26.5%; the nano structure has the characteristics of being degradable under set laser radiation while fully utilizing high photothermal conversion efficiency and drug loading rate of the nano structure, so that the nano structure has the overall degradable characteristic, the biotoxicity is reduced, and the application prospect of the nano structure in the field of biomedicine is widened.
The present invention will be described in further detail with reference to the accompanying drawings and specific embodiments.
Drawings
FIG. 1 is a TEM photograph of degradable antimony nanostructures for synergistic chemotherapy and photothermal therapy, prepared in example 1 of the present invention;
FIG. 2 is a thermal image of degradable antimony nanostructures for synergistic chemotherapy and photothermal therapy prepared in example 1 of the present invention;
FIG. 3 is a drug release profile of the degradable antimony nanostructure for synergistic chemotherapy and photothermal therapy prepared in example 1 of the present invention;
FIG. 4 shows the cell survival rate of the degradable antimony nanostructure for synergistic chemotherapy and photothermal therapy, prepared in example 1 of the present invention.
Fig. 5 is a uv-vis absorption spectrum (degradation rate) of the degradable antimony nanostructure for synergistic chemotherapy and photothermal therapy prepared in example 1 of the present invention.
Detailed Description
Example 1
Referring to fig. 1 to 5, in the degradable antimony nano-structure provided in this embodiment, an anticancer drug doxorubicin hydrochloride is loaded on the surface of the degradable antimony nano-particle; the antimony nano particles have electronegativity, perform electrostatic interaction with doxorubicin hydrochloride with positive charge, and have good water solubility after the surface of the formed nano structure is further modified by an organic ligand; and the whole nanostructure can be degraded under the set laser radiation.
The core of the preparation method of the degradable antimony nanostructure is a method for synthesizing antimony nanoparticles by using a direct reduction method and then loading adriamycin hydrochloride anticancer drugs to obtain the degradable antimony nanostructure for synergistic chemotherapy and photothermal physiotherapy, and the preparation method comprises the following steps:
1) dissolving sodium borohydride serving as a reducing agent in N-methyl-2-pyrrolidone (NMP), ultrasonically dispersing, placing in an oil bath, and stirring for dispersing to obtain a first dispersion liquid;
specifically, the method comprises the following steps: dissolving sodium borohydride in N-methyl-2-pyrrolidone, ultrasonically dispersing for 30min, placing the mixture in an oil bath pot, and continuously stirring until the temperature rises to 60 ℃ to obtain a first dispersion liquid.
2) Dissolving antimony chloride in N-methyl-2-pyrrolidone, adding into the first dispersion, continuously stirring, and obtaining antimony nanoparticles after crystal growth to obtain a second dispersion;
specifically, the method comprises the following steps: firstly, ultrasonically dissolving antimony chloride in N-methyl-2-pyrrolidone, then quickly adding the antimony chloride into the first dispersion liquid, uniformly mixing, continuously stirring for 2 hours, centrifugally washing, and re-dispersing in deionized water to obtain a second dispersion liquid.
3) Mixing the obtained second dispersion with doxorubicin hydrochloride (DOX) anticancer drug, and continuously stirring to obtain an antimony nanostructure loaded by doxorubicin hydrochloride, so as to obtain a third dispersion;
specifically, the method comprises the following steps: and dissolving DOX in deionized water, uniformly mixing with the second dispersion, stirring overnight in a dark place, centrifugally washing, and re-dispersing in ultrapure water to obtain a third dispersion.
4) And fully stirring and mixing the water-soluble surface organic ligand and the third dispersion liquid to obtain the degradable antimony nano structure for the cooperative chemotherapy and photo-thermal physiotherapy, wherein the degradable antimony nano structure is formed by loading adriamycin hydrochloride anticancer drugs on the surfaces of antimony nano particles.
Specifically, the method comprises the following steps: and dissolving polyacrylic acid (PAA) serving as a surface organic ligand in deionized water, performing ultrasonic dispersion, fully stirring and mixing with the third dispersion liquid, and performing centrifugal washing to obtain the degradable antimony nanostructure for synergistic chemotherapy and photothermal physiotherapy.
The water-soluble surface organic ligand in the step 4) comprises: polyvinylpyrrolidone (PVP), polyethylene glycol (PEG), polyacrylic acid (PAA), Polyethyleneimine (PEI).
More specifically:
(1) dissolving 300mg of sodium borohydride in 25mL of N-methyl-2-pyrrolidone, ultrasonically dispersing for 30min, placing the mixture in an oil bath pot, continuously stirring until the temperature rises to 60 ℃, and maintaining at the temperature for 30min to obtain a first dispersion liquid.
(2) Dissolving 3.5g of antimony chloride in 5mL of N-methyl-2-pyrrolidone, quickly adding the antimony chloride into the first dispersion, uniformly mixing, continuously stirring for 2h at 60 ℃, centrifugally washing, and re-dispersing in 10mL of deionized water to obtain a second dispersion.
(3) Dissolving 8mgDOX in 4mL of deionized water, mixing with the second dispersion liquid uniformly, adjusting the pH of the solution to 7.5, stirring overnight in the dark, centrifuging, washing, and dispersing again in ultrapure water to obtain a third dispersion liquid.
(4) Dissolving 50mg of polyacrylic acid (PAA) as a surface organic ligand in 10mL of deionized water, performing ultrasonic dispersion, fully stirring and mixing with the third dispersion, and performing centrifugal washing to obtain the degradable antimony nanostructure for synergistic chemotherapy and photothermal physiotherapy.
When the degradable antimony nanostructure prepared by the embodiment is used as a diagnosis and treatment preparation for synergistic chemotherapy and photothermal physiotherapy, through experimental tests, the photothermal conversion efficiency can reach 40-50%, and the drug loading rate can reach 26.5%; the nano-structure has the characteristics of overall degradability under set laser radiation while fully utilizing the high photothermal conversion efficiency and the drug loading rate of the nano-structure, reduces the biotoxicity and widens the application prospect of the nano-structure in the field of biomedicine.
Referring to fig. 1, which is a TEM photograph of a degradable antimony nanostructure for synergistic chemotherapy and photothermal therapy prepared in embodiment 1 of the present invention, it can be seen from the drawing that the dispersibility of the nanostructure is good and the morphology is uniform, which indicates that the method can effectively control the monodispersity and the morphology of the nanostructure, the average particle size of the nanostructure modified by the organic ligand is-40 nm, the hydrated particle size is about 110nm, and the small-sized nanoparticle is more easily endocytosed by cells, thus being beneficial to circulation in vivo, and having important significance for biological therapy.
FIG. 2 is a photograph of the degradable antimony nanostructures used in photothermal imaging, obtained in example 1 of the present invention, in conjunction with chemotherapy and photothermal therapy. After 808nm laser radiation is used, the temperature of the sample is gradually increased along with the increase of the concentration of the sample, the temperature (delta T) increased under the condition of the maximum sample concentration can reach about 31.2 ℃, and the photothermal conversion efficiency can reach 40-50% through calculation, so that the nano system has good photothermal effect.
FIG. 3 is the drug release curve of the degradable antimony nanostructure for synergistic chemotherapy and photothermal therapy obtained in example 1 of the present invention. As can be seen from the figure, the prepared nanostructure has pH-responsive drug release characteristics, and doxorubicin hydrochloride is released more under acidic conditions (pH 5.0); and the laser irradiation can further improve the drug release amount. This is because laser irradiation can cause degradation of the antimony nanostructure, thereby further increasing the drug release rate.
FIG. 4 is the cell viability of the degradable antimony nanostructures obtained in example 1 of the present invention after incubation with different concentrations of the second and third dispersions. From the figure, we can see that when the HeLa cells are incubated with the second dispersion and the third dispersion, the photothermal therapy alone has better effect than the chemotherapeutic effect caused by the release of the drug alone, and the cell survival rate is lower; however, it is worth noting that the survival rate of the cells of the third dispersion liquid under the illumination is the lowest, which indicates that the nano system shows good treatment effects of the synergistic chemotherapy and the photothermal therapy.
FIG. 5 is the UV-VIS absorption spectrum of the degradable antimony nanostructure for synergistic chemotherapy and photothermal therapy obtained in example 1 of the present invention without laser irradiation and after laser irradiation. As can be seen from the figure, after the laser irradiation at 808nm for 5-10min, the absorbance of the nanostructure at 500-800nm is obviously reduced, which indicates that the structure is degraded after the nanostructure is irradiated by light, so that the absorbance is reduced.
Example 2
The degradable antimony nanostructure, the preparation method and the application thereof provided in this embodiment are substantially the same as those in embodiment 1, except that the degradable antimony nanostructure comprises the following steps:
(1) dissolving 280mg of sodium borohydride in 25mL of N-methyl-2-pyrrolidone, ultrasonically dispersing for 30min, placing the mixture in an oil bath pot, continuously stirring until the temperature rises to 60 ℃, and maintaining at the temperature for 30min to obtain a first dispersion liquid.
(2) Dissolving 3.8g of antimony chloride in 5mL of N-methyl-2-pyrrolidone, quickly adding the antimony chloride into the first dispersion, uniformly mixing, continuously stirring for 2h at 60 ℃, centrifugally washing, and re-dispersing in 10mL of deionized water to obtain a second dispersion.
(3) Dissolving 8.1mg of DOX in 4mL of deionized water, uniformly mixing with the second dispersion, adjusting the pH value of the solution to 7.5, stirring overnight in the dark, centrifugally washing, and re-dispersing in ultrapure water to obtain a third dispersion.
(4) And dissolving 55mg of surface organic ligand polyvinylpyrrolidone (PVP) in 10mL of deionized water, performing ultrasonic dispersion, fully stirring and mixing with the third dispersion liquid, and performing centrifugal washing to obtain the degradable antimony nanostructure for synergistic chemotherapy and photothermal physiotherapy.
Example 3
The degradable antimony nanostructure, the preparation method and the application thereof provided by the embodiment are basically the same as those of the embodiments 1 and 2, and the difference is that the degradable antimony nanostructure comprises the following steps:
(1) 290mg of sodium borohydride is dissolved in 25mL of N-methyl-2-pyrrolidone, ultrasonic dispersion is carried out for 30min, the mixture is placed in an oil bath pot, stirring is carried out continuously until the temperature rises to 60 ℃, and the temperature is maintained for 30min, so that first dispersion liquid is obtained.
(2) Dissolving 3.5g of antimony chloride in 5mL of N-methyl-2-pyrrolidone, quickly adding the antimony chloride into the first dispersion, uniformly mixing, continuously stirring for 2h at 60 ℃, centrifugally washing, and re-dispersing in 10mL of deionized water to obtain a second dispersion.
(3) Dissolving 8mg of DOX in 4mL of deionized water, uniformly mixing with the second dispersion, adjusting the pH value of the solution to 7.5, stirring overnight in a dark place, centrifugally washing, and re-dispersing in ultrapure water to obtain a third dispersion.
(4) Dissolving 50mg of surface organic ligand polyethylene glycol (PEG) in 10mL of deionized water, performing ultrasonic dispersion, fully stirring and mixing with the third dispersion liquid, and performing centrifugal washing to obtain the degradable antimony nanostructure for synergistic chemotherapy and photothermal physiotherapy.
Example 4
The degradable antimony nanostructure, the preparation method and the application thereof provided by the embodiment are basically the same as those in the embodiments 1 to 3, and the difference is that the degradable antimony nanostructure comprises the following steps:
1) dissolving 280mg of sodium borohydride in 25mL of N-methyl-2-pyrrolidone, ultrasonically dispersing for 30min, placing the mixture in an oil bath pot, continuously stirring until the temperature rises to 60 ℃, and maintaining at the temperature for 30min to obtain a first dispersion liquid.
(2) Dissolving 3.9g of antimony chloride in 5mL of N-methyl-2-pyrrolidone, quickly adding the antimony chloride into the first dispersion, uniformly mixing, continuously stirring for 2h at 60 ℃, centrifugally washing, and re-dispersing in 10mL of deionized water to obtain a second dispersion.
(3) Dissolving 8.1mg of DOX in 4mL of deionized water, uniformly mixing with the second dispersion, adjusting the pH value of the solution to 7.5, stirring overnight in the dark, centrifugally washing, and re-dispersing in ultrapure water to obtain a third dispersion.
(4) And dissolving 60mg of surface organic ligand Polyethyleneimine (PEI) in 10mL of deionized water, performing ultrasonic dispersion, fully stirring and mixing with the third dispersion liquid, and performing centrifugal washing to obtain the degradable antimony nanostructure for synergistic chemotherapy and photothermal physiotherapy.
The key point of the invention is that the degradable antimony nanostructure for synergistic chemotherapy and photothermal physiotherapy and the preparation method thereof provided by the invention are characterized in that the key components and the proportion are controlled, a direct reduction method is adopted, antimony nanoparticles are obtained by reduction by utilizing the reducibility of sodium borohydride, and the degradable antimony nanostructure for synergistic chemotherapy and photothermal physiotherapy is obtained after the amorphous drug hydrochloride is loaded. The preparation method effectively overcomes the defects of the existing method, the preparation process flow is simple, the reaction condition is mild, the process is easy to control, the repeatability is good, the equipment investment is low, the cost is low, the obtained nano-junction nano-structure has uniform appearance, uniform size and good biocompatibility, and has high drug loading rate and photo-thermal conversion efficiency, stable yield and quality and easy industrialization.
The present invention is not limited to the above embodiments, and other degradable antimony nanostructures for synergistic chemotherapy and photothermal therapy and their preparation methods, such as polyacrylic acid (PAA), polyvinylpyrrolidone (PVP), polyethylene glycol (PEG), Polyethyleneimine (PEI)) using different organic ligands, which are obtained by the same or similar methods, are within the scope of the present invention.
Claims (8)
1. A degradable antimony nano-structure is characterized in that the nano-structure is formed by loading an anticancer drug adriamycin hydrochloride on the surface of degradable antimony nano-particles; the antimony nano particles have electronegativity, and have electrostatic interaction with doxorubicin hydrochloride with positive charge, and after the surface of the formed nano structure is further modified by an organic ligand, the antimony nano particles have good water solubility, good dispersibility, uniform appearance and uniform size, the average particle size of the granular nano structure modified by the organic ligand is 40nm, the average particle size of hydrated particle size is 110nm, and the nano structure is more easily endocytosed by cells and is beneficial to circulation in organisms; and the whole nano structure is degraded after 808nm laser radiation for 5-10min, so that the biological toxicity is reduced.
2. The method for preparing the degradable antimony nanostructure according to claim 1, comprising the steps of:
1) dissolving sodium borohydride serving as a reducing agent in N-methyl-2-pyrrolidone (NMP), ultrasonically dispersing, placing in an oil bath, and uniformly stirring to obtain a first dispersion liquid;
2) dissolving antimony chloride in N-methyl-2-pyrrolidone, adding into the first dispersion, continuously stirring, and obtaining antimony nanoparticles after crystal growth to obtain a second dispersion;
3) mixing the obtained second dispersion with doxorubicin hydrochloride (DOX) anticancer drug, and continuously stirring to obtain an antimony nanostructure loaded by doxorubicin hydrochloride, so as to obtain a third dispersion;
4) and fully stirring and mixing the water-soluble surface organic ligand and the third dispersion liquid to obtain the degradable antimony nano structure for the cooperative chemotherapy and photo-thermal physiotherapy, wherein the degradable antimony nano structure is a granular degradable nano structure with the average grain diameter of 40nm formed by loading adriamycin hydrochloride anti-cancer drugs on the surfaces of antimony nano particles.
3. The method for preparing the degradable antimony nanostructure according to claim 2, wherein the first dispersion liquid in the step 1) comprises the following specific steps:
dissolving 280-300mg sodium borohydride in 25mL of N-methyl-2-pyrrolidone, ultrasonically dispersing for 30min, placing the mixture in an oil bath pot, and continuously stirring until the temperature is raised to 60 ℃ to obtain a first dispersion liquid.
4. The method for preparing the degradable antimony nanostructure according to claim 2, wherein the step 2) of the second dispersion comprises the following specific steps:
firstly, dissolving 3.5-4.0g of antimony chloride in 5mL of N-methyl-2-pyrrolidone by ultrasonic, then quickly adding the antimony chloride into the first dispersion liquid, uniformly mixing, continuously stirring for 2h, centrifugally washing, and re-dispersing in 10mL of deionized water to obtain a second dispersion liquid.
5. The method for preparing the degradable antimony nanostructure according to claim 2, wherein the step 3) of the third dispersion comprises the following specific steps:
dissolving 8-8.1mg of DOX in 4mL of deionized water, uniformly mixing with the second dispersion, stirring overnight in the dark, centrifugally washing, and re-dispersing in ultrapure water to obtain a third dispersion.
6. The method for preparing the degradable antimony nanostructure according to claim 2, wherein the specific steps of the step 4) are as follows:
dissolving 50-60mg of surface organic ligand polyacrylic acid (PAA) in 10mL of deionized water, performing ultrasonic dispersion, fully stirring and mixing with the third dispersion, and performing centrifugal washing to obtain the degradable antimony nanostructure for synergistic chemotherapy and photothermal physiotherapy.
7. The method for preparing the degradable antimony nanostructure according to claim 2, wherein the water-soluble surface organic ligand in the step 4) comprises: polyacrylic acid (PAA), polyvinylpyrrolidone (PVP), polyethylene glycol (PEG), Polyethyleneimine (PEI).
8. Use of the degradable antimony nanostructures of claim 1 for the preparation of a diagnostic formulation for synergistic chemotherapy and photothermal therapy.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910221673.2A CN109966490B (en) | 2019-03-22 | 2019-03-22 | Degradable antimony nanostructure, preparation method and application |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910221673.2A CN109966490B (en) | 2019-03-22 | 2019-03-22 | Degradable antimony nanostructure, preparation method and application |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN109966490A CN109966490A (en) | 2019-07-05 |
| CN109966490B true CN109966490B (en) | 2021-10-15 |
Family
ID=67080094
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201910221673.2A Active CN109966490B (en) | 2019-03-22 | 2019-03-22 | Degradable antimony nanostructure, preparation method and application |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN109966490B (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110938423B (en) * | 2019-08-28 | 2022-09-23 | 上海大学 | Degradable antimony-coated rare earth upconversion nanocomposite structure, preparation method and application |
| CN112618715B (en) * | 2021-01-06 | 2023-03-14 | 浙江理工大学 | Preparation method of drug-loaded photothermal photodynamic nanoparticles based on electrostatic adsorption |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101081436A (en) * | 2007-07-03 | 2007-12-05 | 杭州电子科技大学 | Process for producing zinc antimonide powder at low temperature |
| WO2012031282A2 (en) * | 2010-09-03 | 2012-03-08 | Tufts University/Trustees Of Tufts College | Plasmonic nanoparticle-doped silk materials |
| CN104900858A (en) * | 2015-06-15 | 2015-09-09 | 中南大学 | Preparation method for sodium-ion battery antimony/carbon anode composite material with yolk-shell structure |
| CN108524956A (en) * | 2018-05-07 | 2018-09-14 | 北京工业大学 | A kind of photoacoustic imaging contrast agent |
-
2019
- 2019-03-22 CN CN201910221673.2A patent/CN109966490B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101081436A (en) * | 2007-07-03 | 2007-12-05 | 杭州电子科技大学 | Process for producing zinc antimonide powder at low temperature |
| WO2012031282A2 (en) * | 2010-09-03 | 2012-03-08 | Tufts University/Trustees Of Tufts College | Plasmonic nanoparticle-doped silk materials |
| CN104900858A (en) * | 2015-06-15 | 2015-09-09 | 中南大学 | Preparation method for sodium-ion battery antimony/carbon anode composite material with yolk-shell structure |
| CN108524956A (en) * | 2018-05-07 | 2018-09-14 | 北京工业大学 | A kind of photoacoustic imaging contrast agent |
Non-Patent Citations (4)
| Title |
|---|
| "Black Phosphorus-Based Drug Nanocarrier for Targeted and Synergetic Chemophotothermal Therapy of Acute Lymphoblastic Leukemia";Shenfei Zong et al;《ACS Appl. Mater. Interfaces》;20190122;第11卷;第5896-5902页 * |
| "NIR Light-Degradable Antimony Nanoparticle-Based Drug-Delivery Nanosystem for Synergistic Chemo−Photothermal Therapy in Vitro";Solomon Tiruneh Dibaba et al;《ACS Appl. Mater. Interfaces》;20191205;第11卷;第48290-48299页 * |
| "Semimetal nanomaterials of antimony as highly efficient agent for photoacoustic imaging and photothermal therapy";Wanwan Li et al;《Biomaterials》;20150113;第45卷;第18-26页 * |
| Antimonene Quantum Dots: Synthesis and Application as Near-Infrared Photothermal Agents for Effective Cancer Therapy";Wei Tao et al;《Angew. Chem. Int. Ed》;20170717;第56卷;第11896-11900页 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN109966490A (en) | 2019-07-05 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Wei et al. | Biomedical and bioactive engineered nanomaterials for targeted tumor photothermal therapy: A review | |
| Wang et al. | Construction of nanomaterials with targeting phototherapy properties to inhibit resistant bacteria and biofilm infections | |
| Zhang et al. | Near-infrared light triggered photo-therapy, in combination with chemotherapy using magnetofluorescent carbon quantum dots for effective cancer treating | |
| Wang et al. | Ag@ Fe3O4@ C nanoparticles for multi-modal imaging-guided chemo-photothermal synergistic targeting for cancer therapy | |
| Yang et al. | Recent advances in nanosized metal organic frameworks for drug delivery and tumor therapy | |
| CN104474559B (en) | Hollow mesoporous prussian blue nano photo-thermal diagnosis and treatment agent with ultrasound contrast function and preparation method of hollow mesoporous prussian blue nano photo-thermal diagnosis and treatment agent | |
| CN105031671B (en) | Based on Prussian blue synergic nano diagnosis and treatment agent of intelligent pH triggering MRI monitoring insoluble drug releases and preparation method thereof | |
| US11007207B2 (en) | Preparations of gold/mesoporous silica hybrid nanoparticle and applications | |
| CN107899011B (en) | Manganese and dopamine-based tumor diagnosis and treatment nano material and preparation method and application thereof | |
| Gao et al. | AuNRs@ MIL-101-based stimuli-responsive nanoplatform with supramolecular gates for image-guided chemo-photothermal therapy | |
| CN111529510A (en) | Application of nanoparticles as tumor microenvironment responsive drug or imaging agent | |
| CN109966490B (en) | Degradable antimony nanostructure, preparation method and application | |
| CN106729738A (en) | A kind of dendritic golden platinum bimetal nano particles and its preparation method and application | |
| CN111481737A (en) | Magnetic temperature-sensitive hydrogel for near-infrared light-controlled release of nitric oxide, and preparation and application thereof | |
| Sun et al. | A Pd corolla–human serum albumin–indocyanine green nanocomposite for photothermal/photodynamic combination therapy of cancer | |
| Lu et al. | Multifunctional Cu1. 94S-Bi2S3@ polymer nanocomposites for computed tomography imaging guided photothermal ablation | |
| CN113577273B (en) | Copper and manganese doped Prussian blue-like-molybdenum disulfide nano composite material and preparation and application thereof | |
| Zhang et al. | Structure Engineered High Piezo‐Photoelectronic Performance for Boosted Sono‐Photodynamic Therapy | |
| KR101213409B1 (en) | Aqueous dispersion of near-infrared photothermal organic nanoparticles, and preparation method and use thereof | |
| CN113082213A (en) | Hollow copper sulfide nano-drug carrier, preparation method and application | |
| CN108030932A (en) | Mesoporous Fe3O4Composite material and preparation method thereof and the application in tumour MRI radiographies and photo-thermal/chemotherapy synergistic treatment | |
| CN109550050B (en) | Melanin-loaded molybdenum dioxide drug-loaded compound and preparation and application thereof | |
| CN111686250A (en) | Mitochondrion targeted photothermal therapeutic agent and preparation and application thereof | |
| CN115025065B (en) | Stimulation-responsive multifunctional targeted micro robot and preparation method and application thereof | |
| CN114177289A (en) | Composite nano material for photodynamic and photothermal combined treatment and preparation method and application thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |