CN110755643A - Positive contrast agent and preparation method and application thereof - Google Patents

Positive contrast agent and preparation method and application thereof Download PDF

Info

Publication number
CN110755643A
CN110755643A CN201911187524.5A CN201911187524A CN110755643A CN 110755643 A CN110755643 A CN 110755643A CN 201911187524 A CN201911187524 A CN 201911187524A CN 110755643 A CN110755643 A CN 110755643A
Authority
CN
China
Prior art keywords
contrast agent
positive contrast
protein
solution
ferrous
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.)
Granted
Application number
CN201911187524.5A
Other languages
Chinese (zh)
Other versions
CN110755643B (en
Inventor
张兵波
杨维涛
徐琰
曾维薇
刘凯
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Tongji University
Original Assignee
Tongji University
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Tongji University filed Critical Tongji University
Priority to CN201911187524.5A priority Critical patent/CN110755643B/en
Publication of CN110755643A publication Critical patent/CN110755643A/en
Application granted granted Critical
Publication of CN110755643B publication Critical patent/CN110755643B/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Images

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K49/00Preparations for testing in vivo
    • A61K49/06Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations
    • A61K49/08Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by the carrier
    • A61K49/10Organic compounds
    • A61K49/14Peptides, e.g. proteins
    • A61K49/143Peptides, e.g. proteins the protein being an albumin, e.g. HSA, BSA, ovalbumin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K49/00Preparations for testing in vivo
    • A61K49/06Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations
    • A61K49/08Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by the carrier
    • A61K49/10Organic compounds
    • A61K49/14Peptides, e.g. proteins
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K49/00Preparations for testing in vivo
    • A61K49/06Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations
    • A61K49/18Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by a special physical form, e.g. emulsions, microcapsules, liposomes
    • A61K49/1818Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by a special physical form, e.g. emulsions, microcapsules, liposomes particles, e.g. uncoated or non-functionalised microparticles or nanoparticles
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K1/00General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
    • C07K1/107General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length by chemical modification of precursor peptides
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K14/00Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/76Albumins
    • C07K14/765Serum albumin, e.g. HSA
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K14/00Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/79Transferrins, e.g. lactoferrins, ovotransferrins

Abstract

The invention discloses a positive contrast agent and a preparation method and application thereof, wherein the positive contrast agent comprises the following components: proteins and iron-based nanoparticles. The positive contrast agent prepared by the invention has the advantages of good biocompatibility, smaller size, higher relaxation efficiency and the like, and the preparation method also realizes green production.

Description

Positive contrast agent and preparation method and application thereof
Technical Field
The invention belongs to the technical field of magnetic resonance imaging, and particularly relates to a positive contrast agent, and a preparation method and application thereof.
Background
The magnetic resonance contrast agents commonly used at present are mainly divided into two types, one type is a micromolecule positive contrast agent represented by maguey (Gd-DTPA), and longitudinal relaxation time (T) is shortened1) To cause a diseaseThe part becomes brighter than the normal tissue signal; another class of negative contrast agents, represented by ferrocarbamate, by shortening the transverse relaxation time (T)2) So that the diseased region becomes darker relative to normal tissue signals. However, both of these classes of contrast agents currently have limitations during use: such as the single function, the over-rapid metabolism of small molecule positive contrast agents, and the susceptibility to systemic fibrosis of renal origin; negative contrast agents are often not clinically favored over positive contrast agents because of the large size, poor contrast, low sensitivity, and other problems. Therefore, there is an urgent need to develop safer and more effective magnetic resonance contrast agents.
Disclosure of Invention
In order to overcome the defects of the prior art, the invention aims to provide a positive contrast agent, a preparation method and an application thereof, the prepared positive contrast agent has the advantages of good biocompatibility, smaller size, higher relaxation efficiency and the like, and the preparation method also realizes green production.
In order to achieve the above and other objects, the present invention provides a positive contrast agent, including:
a protein;
iron-based nanoparticles, wherein the iron-based nanoparticles are grown on the surface of the protein.
In one embodiment, the protein is one or both of serum protein or ferritin.
In one embodiment, the iron-based nanoparticles are ferrous sulfide nanoparticles.
Another object of the present invention is to provide a method for preparing a positive contrast agent, which at least comprises the following steps:
providing a reaction medium;
chelating ferrous salt ions on the protein through the reaction medium to obtain a precursor solution;
under an alkaline condition, adding a sulfur source into the precursor solution to grow iron-based nanoparticles on the surface of the protein to obtain an intermediate solution;
and (4) dialyzing and lyophilizing the intermediate solution to obtain the positive contrast agent.
In one embodiment, the reaction medium is water.
In one embodiment, the intermediate solution is obtained by adding a sulfur source to the precursor solution at a temperature of 25-40 ℃ and continuing the reaction for 2-4 hours.
In one embodiment, the source of the ferrous salt ions comprises one or more of ferrous chloride, ferrous nitrate, ferrous sulfate, or ferrous acetate.
In one embodiment, the sulfur source is sodium sulfide hydrate.
In one embodiment, the mass ratio of the ferrous salt ions to the sulfur source is (1:1) - (1: 8).
In one embodiment, the alkaline condition is formed by adjusting the pH value of the precursor solution to 10-12 through a sodium hydroxide solution with the concentration of 1-2 mol/L.
Another object of the present invention is to provide a use of the positive contrast agent, which is applied to magnetic resonance imaging.
The positive contrast agent prepared by the invention is prepared by adopting a protein simulation bionic technology, and the technology has the characteristics of simple and convenient preparation process, green and mild reaction conditions, low energy consumption, good environmental compatibility, low cost and easy clinical transformation. The positive contrast agent prepared by the invention has good biocompatibility and can effectively avoid the prior T1The magnetic resonance contrast agent has the defects of over-rapid metabolism, easy renal fibrosis and the like. The invention has certain universality, can control and synthesize other nano-particles with different shapes, sizes and functions by using other proteins, and is used in the field of biotechnology.
Drawings
FIG. 1 is a schematic flow chart of a preparation method in one embodiment;
FIG. 2 is a schematic diagram of the distribution of iron-based nanoparticles on the surface of a protein in the positive contrast agent A according to an embodiment;
FIG. 3 is partial longitudinal relaxation efficiency data for positive contrast agent A in one embodiment;
FIG. 4 shows T of positive contrast agent A in an embodiment1A magnetic resonance imaging schematic diagram;
FIG. 5 is partial longitudinal relaxation efficiency data for positive contrast agent B in one embodiment;
FIG. 6 is partial longitudinal relaxation efficiency data for positive contrast agent C in one embodiment;
FIG. 7 is data of elemental composition of positive contrast agent D in one embodiment.
Detailed Description
The following description of the embodiments of the present invention is provided by way of specific examples, and other advantages and effects of the present invention will be readily apparent to those skilled in the art from the disclosure herein. The invention is capable of other and different embodiments and of being practiced or of being carried out in various ways, and its several details are capable of modification in various respects, all without departing from the spirit and scope of the present invention. It is to be noted that the features in the following embodiments and examples may be combined with each other without conflict. It is also to be understood that the terminology used in the examples is for the purpose of describing particular embodiments only, and is not intended to limit the scope of the present invention. Test methods in which specific conditions are not specified in the following examples are generally carried out under conventional conditions or under conditions recommended by the respective manufacturers.
When numerical ranges are given in the examples, it is understood that both endpoints of each of the numerical ranges and any value therebetween can be selected unless the invention otherwise indicated. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs and the description of the present invention, and any methods, apparatuses, and materials similar or equivalent to those described in the examples of the present invention may be used to practice the present invention.
In the present specification, the term "T1 contrast agent" refers to a positive contrast agent (positivecontrast agent) that forms an image signal of a body part, an image of which is required to be obtained, in a relatively high manner as compared with the surroundings, thereby brightening the part to be diagnosed.
The invention provides a positive contrast agent, a preparation method and an application thereof, wherein the positive contrast agent is used as a T1 contrast agent in magnetic resonance imaging.
Referring to fig. 1, a method for preparing a positive contrast agent is provided, which at least includes the following steps:
s1, providing a reaction medium;
s2, chelating ferrous salt ions on the protein through the reaction medium to obtain a precursor solution;
s3, adding a sulfur source into the precursor solution under an alkaline condition to enable iron-based nanoparticles to grow on the surface of the protein, and obtaining an intermediate solution;
s4, dialyzing and lyophilizing the intermediate solution to obtain the positive contrast agent.
The present invention will be specifically described from step S1 to step S4.
In step S1, the reaction medium is, for example, water.
In step S2, the source of the ferrous salt ions includes one or more of ferrous chloride, ferrous nitrate, ferrous sulfate, or ferrous acetate. The protein is one or two of serum protein or ferritin. The protein is protein in a protein solution, the concentration of the protein solution is 6.25-25mg/mL, the protein concentration of the application can change the hydrodynamic particle size of the protein nanoparticles, and the protein particle size of the application is easier for growing iron-based nanoparticles.
In step S3, the pH value of the precursor solution is adjusted to 10-12 by sodium hydroxide solution with the concentration of 1-2mol/L under alkaline condition. And adding a sulfur source into the precursor solution at the temperature of 25-40 ℃ and continuously reacting for 2-4 hours to obtain the intermediate solution. The mass ratio of the ferrous salt ions to the sulfur source is (1:1) - (1: 8). The sulfur source is sodium sulfide hydrate.
In step S4, after the step S3 is finished, the intermediate solution is taken out, added into a dialysis bag with the molecular weight cutoff of 8000- "14000, placed into a beaker containing ultrapure water, and dialyzed for 24-48 hours, wherein the water is changed for 5-6 times. And collecting the dialyzed solution, storing the solution at-80 ℃ for 3-4 hours, putting the solution into a freeze-drying bottle for freeze-drying and concentration treatment, and finally obtaining the freeze-dried positive contrast agent.
It is also an object of the present invention to provide a positive contrast agent comprising: a protein and iron-based nanoparticles, wherein the iron-based nanoparticles are grown on the surface of the protein.
The present invention is specifically illustrated by the following examples.
Referring to FIGS. 2-4, partial data of positive contrast agent A obtained by an example, the longitudinal relaxation efficiency was 5.35mM-1s-1The specific preparation process of the positive contrast agent A comprises the following steps: in one embodiment, 200-250mg of Human Serum Albumin (HSA) powder is accurately weighed, 8-10mL of ultrapure water is added, and ultrasonic oscillation is carried out for dissolution to obtain a human serum albumin solution with the concentration of 20-50 mg/mL; taking 0.03-0.05mmol of FeCl2·4H2Adding O into the human serum albumin solution, and continuously stirring for 3-5 minutes at normal temperature. Preparing NaOH solution with the concentration of 1-2mol/L, adding 0.5-1mL of the NaOH solution into a reaction bottle, and adjusting the pH value of the system to 11-12. Taking 0.06-0.07mmol of Na2S·9H2Adding the O solution into the reaction system, and continuously reacting for 2-4 hours at 35-37 ℃. After the reaction is finished, the solution is taken out, added into a dialysis bag with the molecular weight cutoff of 8000-14000, placed into a beaker filled with ultrapure water, and dialyzed for 24-48 hours, wherein the water is changed for 5-6 times. Collecting the dialyzed solution, storing at-80 deg.C for 3-4 hr, freeze-drying and concentrating in a freeze-drying bottle to obtain freeze-dried positive contrast agent, and recording as positive contrast agent A. The size of the positive contrast agent A prepared under the embodiment is 3-4nm, and the longitudinal relaxation efficiency can reach 5.35-5.5mM-1s-1. FIG. 3 is a graph showing that the longitudinal relaxation efficiency reaches 5.35mM in one embodiment-1s-1With reference to FIG. 4, the positive contrast agent A has a good T1Referring to fig. 2, the iron-based nanoparticles in the positive contrast agent a uniformly grow on the surface of the protein, and the dispersibility is very good.
Referring to FIG. 5, a partial data of the positive contrast agent B prepared by an example shows that the longitudinal relaxation efficiency can reach 5.0mM-1s-1The specific preparation process of the positive contrast agent B is as follows: in one embodiment, for example, 120-125mg of Human Serum Albumin (HSA) powder is accurately weighed, 8-10mL of ultrapure water is added, and the mixture is dissolved by ultrasonic oscillation to obtain a human serum albumin solution with a concentration of 12-16 mg/mL. Taking 0.03-0.05mmol of FeCl2·4H2O is added into the human serum albumin solution and is continuously stirred for 3 to 5 minutes at normal temperature. Preparing NaOH solution with the concentration of 1-2mol/L, adding 0.5-1mL of the NaOH solution into a reaction bottle, and adjusting the pH value of the reaction system to 11-12. Taking 0.03-0.05mmol of Na2S·9H2Adding the O solution into the reaction system, and continuously reacting for 2-4 hours at 35-37 ℃. After the reaction is finished, the solution is taken out, added into a dialysis bag with the molecular weight cutoff of 8000-14000, placed into a beaker filled with ultrapure water, and dialyzed for 24-48 hours, wherein the water is changed for 5-6 times. Collecting dialyzed solution, storing at-80 deg.C for 3-4 hr, freeze drying and concentrating in a freeze drying bottle to obtain freeze dried positive contrast agent, and recording as positive contrast agent B with longitudinal relaxation efficiency of 4.9-5.0mM-1s-1. Referring to FIG. 5, an embodiment of the longitudinal relaxation efficiency of 5.0mM is shown-1s-1Schematic representation of (a). The contrast agent prepared in this example had good T1Magnetic resonance imaging effect.
Referring to FIG. 6, a partial data of positive contrast agent C obtained by another example shows that the longitudinal relaxation efficiency can reach 4.88mM-1s-1The specific preparation process of the positive contrast agent C comprises the following steps: in one embodiment, 60-62.5mg of Human Serum Albumin (HSA) powder is accurately weighed, 8-10mL of ultrapure water is added, and ultrasonic oscillation is carried out for dissolution to obtain a human serum albumin solution with the concentration of 6-7.81 mg/mL; taking 0.03-0.05mmol of FeCl2·4H2Adding O into the human serum albumin solution, and continuously stirring for 3-5 minutes at normal temperature. Preparing NaOH solution with the concentration of 1mol/L, adding 0.5-1mL of the prepared NaOH solution into a reaction bottle, and adjusting the pH value of the system to 11-12. Taking 0.1-0.12mmol of Na2S·9H2O solution is added into the reaction system at 3The reaction is continued for 2-4 hours at 5-37 ℃. After the reaction is finished, the solution is taken out, added into a dialysis bag with the molecular weight cutoff of 8000-14000, placed into a beaker filled with ultrapure water, and dialyzed for 24-48 hours, wherein the water is changed for 5-6 times. And collecting the dialyzed solution, storing the solution at-80 ℃ for 3-4 hours, putting the solution into a freeze-drying bottle for freeze-drying and concentration treatment, and finally obtaining a freeze-dried positive contrast agent which is marked as a positive contrast agent C. The positive contrast agent C prepared in this example had a longitudinal relaxation efficiency of 4.55-4.88mM-1s-1Referring to FIG. 6, an embodiment with a longitudinal relaxation efficiency of 4.88mM can be obtained-1s-Schematic representation. The contrast agent prepared in this example had good T1Magnetic resonance imaging effect.
Referring to fig. 7, a part of data of a positive contrast agent D obtained by another embodiment, the basic elemental compositions of the positive contrast agent D are Fe and S as shown in fig. 7. The specific preparation process of the positive contrast agent D comprises the following steps: in one embodiment, Human Serum Albumin (HSA) powder, such as 60-62.5mg, is accurately weighed, 8-10mL of ultrapure water is added, and the mixture is dissolved by ultrasonic oscillation to obtain a human serum albumin solution with the concentration of 6.07.81 mg/mL; taking 0.03-0.05mmol of FeCl2·4H2Adding O into the human serum albumin solution, and continuously stirring for 3-5 minutes at normal temperature. Preparing NaOH solution with the concentration of 1-2mol/L, adding 0.2-0.25mL of the prepared NaOH solution into a reaction bottle, and adjusting the pH value of the system to 9-10. Taking 0.2-0.24mmol of Na2S·9H2Adding the O solution into the reaction system, and continuously reacting for 2-4 hours at the temperature of 80-85 ℃. After the reaction is finished, the solution is taken out, added into a dialysis bag with the molecular weight cutoff of 8000-14000, placed into a beaker filled with ultrapure water, and dialyzed for 24-48 hours, wherein the water is changed for 5-6 times. Collecting the dialyzed solution, storing at-80 deg.C for 3-4 hr, freeze-drying and concentrating in a freeze-drying bottle to obtain freeze-dried positive contrast agent, and recording as positive contrast agent D. Referring to FIG. 7, the elemental composition of one embodiment of the contrast agent is Fe and S. The contrast agent prepared in this example had good T1Magnetic resonance imaging effect.
The invention uses protein simulation bionic technology, selects serum protein or ferritin, and usesAmino acid rich in amino, carboxyl or sulfhydryl on protein is chelated with ferrous ion firstly, then the secondary structure of protein is changed under alkaline environment, after sodium sulfide is added, the ferrous ion and sulfur ion rapidly nucleate reaction, and under the action of limited domain of protein, ultra-small protein bionic iron-based T is finally formed1A contrast agent.
Furthermore, it is to be understood that one or more method steps mentioned in the present invention does not exclude that other method steps may also be present before or after the combined steps or that other method steps may also be inserted between these explicitly mentioned steps, unless otherwise indicated; it is also to be understood that a combined connection between one or more devices/apparatus as referred to in the present application does not exclude that further devices/apparatus may be present before or after the combined device/apparatus or that further devices/apparatus may be interposed between two devices/apparatus explicitly referred to, unless otherwise indicated. Moreover, unless otherwise indicated, the numbering of the various method steps is merely a convenient tool for identifying the various method steps, and is not intended to limit the order in which the method steps are arranged or the scope of the invention in which the invention may be practiced, and changes or modifications in the relative relationship may be made without substantially changing the technical content.
The foregoing embodiments are merely illustrative of the principles and utilities of the present invention and are not intended to limit the invention. Any person skilled in the art can modify or change the above-mentioned embodiments without departing from the spirit and scope of the present invention. Accordingly, it is intended that all equivalent modifications or changes which can be made by those skilled in the art without departing from the spirit and technical spirit of the present invention be covered by the claims of the present invention.

Claims (10)

1. A positive contrast agent, comprising:
a protein;
iron-based nanoparticles, wherein the iron-based nanoparticles are grown on the surface of the protein.
2. The positive contrast agent as claimed in claim 1, wherein the protein is one or both of serum protein and ferritin.
3. The positive contrast agent as claimed in claim 1, wherein said iron-based nanoparticles are ferrous sulfide nanoparticles.
4. A method for preparing a positive contrast agent, characterized by comprising at least the following steps:
providing a reaction medium;
chelating ferrous salt ions on the protein through the reaction medium to obtain a precursor solution;
under an alkaline condition, adding a sulfur source into the precursor solution to grow iron-based nanoparticles on the surface of the protein to obtain an intermediate solution;
and (4) dialyzing and lyophilizing the intermediate solution to obtain the positive contrast agent.
5. The method of claim 4, wherein the reaction medium is water.
6. The method of claim 4, wherein the intermediate solution is obtained by adding a sulfur source to the precursor solution at a temperature of 25-40 ℃ and continuing the reaction for 2-4 hours.
7. The method of claim 4, wherein the source of the ferrous salt ion comprises one or more of ferrous chloride, ferrous nitrate, ferrous sulfate, and ferrous acetate.
8. The method of claim 4, wherein the sulfur source is sodium sulfide hydrate.
9. The method of claim 4, wherein the mass ratio of the ferrous salt ion to the sulfur source is (1:1) - (1: 8).
10. Use of a positive contrast agent according to any of claims 1 to 3 for use in magnetic resonance imaging.
CN201911187524.5A 2019-11-28 2019-11-28 Positive contrast agent and preparation method and application thereof Active CN110755643B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201911187524.5A CN110755643B (en) 2019-11-28 2019-11-28 Positive contrast agent and preparation method and application thereof

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201911187524.5A CN110755643B (en) 2019-11-28 2019-11-28 Positive contrast agent and preparation method and application thereof

Publications (2)

Publication Number Publication Date
CN110755643A true CN110755643A (en) 2020-02-07
CN110755643B CN110755643B (en) 2021-04-02

Family

ID=69339798

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201911187524.5A Active CN110755643B (en) 2019-11-28 2019-11-28 Positive contrast agent and preparation method and application thereof

Country Status (1)

Country Link
CN (1) CN110755643B (en)

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20070258889A1 (en) * 2005-11-09 2007-11-08 Montana State University Novel nanoparticles and use thereof
WO2009026141A1 (en) * 2007-08-17 2009-02-26 University Of Florida Research Foundation, Inc. Supercrystalline colloidal particles and method of production
CN104013978A (en) * 2014-06-18 2014-09-03 苏州大学 Polyethylene glycol-modified ferrous sulfide magnetic nanometer treatment agent as well as preparation method and application thereof
EP2982652A1 (en) * 2014-08-08 2016-02-10 Universität für Bodenkultur Wien Ultra-dense shell core-shell nanoparticles
CN105999309A (en) * 2016-05-24 2016-10-12 天津大学 Protein biological template-based gadolinium-doped copper sulfide nano-particles and preparation method thereof
CN107496941A (en) * 2017-09-27 2017-12-22 首都医科大学 A kind of preparation method and applications of gadolinium sulfide nanoparticle

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20070258889A1 (en) * 2005-11-09 2007-11-08 Montana State University Novel nanoparticles and use thereof
WO2009026141A1 (en) * 2007-08-17 2009-02-26 University Of Florida Research Foundation, Inc. Supercrystalline colloidal particles and method of production
CN104013978A (en) * 2014-06-18 2014-09-03 苏州大学 Polyethylene glycol-modified ferrous sulfide magnetic nanometer treatment agent as well as preparation method and application thereof
EP2982652A1 (en) * 2014-08-08 2016-02-10 Universität für Bodenkultur Wien Ultra-dense shell core-shell nanoparticles
CN105999309A (en) * 2016-05-24 2016-10-12 天津大学 Protein biological template-based gadolinium-doped copper sulfide nano-particles and preparation method thereof
CN107496941A (en) * 2017-09-27 2017-12-22 首都医科大学 A kind of preparation method and applications of gadolinium sulfide nanoparticle

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
KAI YANG,ET AL.: "FeS nanoplates as a multifunctional nano-theranostic for magnetic resonance imaging guided photothermal therapy", 《BIOMATERIALS》 *
沈佳: "生物矿化后具有pH响应性的硫化亚铁纳米颗粒用于肿瘤多模态成像及热放疗-化疗协同治疗的研究", 《中国优秀硕士学位论文全文数据库医药卫生科技辑》 *

Also Published As

Publication number Publication date
CN110755643B (en) 2021-04-02

Similar Documents

Publication Publication Date Title
KR100851933B1 (en) Magnetic Resonance Imaging Contrast Agents containing Water-Soluble Nanoparticles of Manganese Oxide or Manganese Metal Oxide
Lee et al. Designed synthesis of uniformly sized iron oxide nanoparticles for efficient magnetic resonance imaging contrast agents
JP5569837B2 (en) Method for producing surface-coated inorganic particles
US7407646B2 (en) Hydrophilic polymer biomaterial having a specific magnetic resonance imaging signal and process for the preparation of said biomaterial
US9352058B2 (en) Method of preparing iron oxide nanoparticles coated with hydrophilic material, and magnetic resonance imaging contrast agent using the same
US5491219A (en) Ferritin with ferrimagnetically ordered ferrite core and method technical field
Liong et al. Carboxymethylated polyvinyl alcohol stabilizes doped ferrofluids for biological applications
CN103025314A (en) Magnetic nanoparticles
CN108295306B (en) Three-dimensional printing hydrogel material containing mesoporous nano calcium phosphate particle filler and preparation method thereof
Kačenka et al. Dual imaging probes for magnetic resonance imaging and fluorescence microscopy based on perovskite manganite nanoparticles
EP2461834A2 (en) Metal oxide particles coated with polyethylene glycol and their synthesis
CN110755643B (en) Positive contrast agent and preparation method and application thereof
US20230138790A1 (en) Multimodal pet/mri contrast agent and a process for the synthesis thereof
Cano et al. Self-assembly of a superparamagnetic raspberry-like silica/iron oxide nanocomposite using epoxy–amine coupling chemistry
Wang et al. Recent advances in development of functional magnetic adsorbents for selective separation of proteins/peptides
Chang et al. Carboxymethylated polyethylenimine modified magnetic nanoparticles specifically for purification of His‐tagged protein
CN108636305B (en) Preparation method of polymer magnetic beads for protein separation
CN114377159A (en) Low-nephrotoxicity protein-iron oxide composite nano magnetic resonance contrast agent as well as preparation method and application thereof
EP1902734A1 (en) uPAR selective contrast agent for magnetic resonance imaging
JP2005060221A (en) Composite material of organic substance and ferrite, and its production method
JP4136715B2 (en) Protein-immobilized magnetic carrier, method for producing the same, and use thereof
KR102108796B1 (en) Double layer nanoparticle complex, preparation method thereof and method for detecting pathogenic bacteria by using the same
US20150338485A1 (en) Metal particle mri contrast agents and methods of use
CN113679854B (en) Magnetic resonance contrast agent and preparation and application thereof
CN113234182B (en) Beta-cyclodextrin arm lectin magnetic material 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