CN111763326A - Gadolinium ion-polyethylene glycol-dendrimer-CD 68 antibody polymer and preparation method and application thereof - Google Patents
Gadolinium ion-polyethylene glycol-dendrimer-CD 68 antibody polymer and preparation method and application thereof Download PDFInfo
- Publication number
- CN111763326A CN111763326A CN202010525997.8A CN202010525997A CN111763326A CN 111763326 A CN111763326 A CN 111763326A CN 202010525997 A CN202010525997 A CN 202010525997A CN 111763326 A CN111763326 A CN 111763326A
- Authority
- CN
- China
- Prior art keywords
- solution
- dendrimer
- polyethylene glycol
- reacting
- stirring
- 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.)
- Pending
Links
- 229920000642 polymer Polymers 0.000 title claims abstract description 32
- 229910052688 Gadolinium Inorganic materials 0.000 title claims abstract description 17
- 239000004698 Polyethylene Substances 0.000 title claims abstract description 17
- UIWYJDYFSGRHKR-UHFFFAOYSA-N gadolinium atom Chemical compound [Gd] UIWYJDYFSGRHKR-UHFFFAOYSA-N 0.000 title claims abstract description 17
- 229920000573 polyethylene Polymers 0.000 title claims abstract description 17
- 238000002360 preparation method Methods 0.000 title claims abstract description 14
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims abstract description 32
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 claims abstract description 21
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims abstract description 21
- 239000007795 chemical reaction product Substances 0.000 claims abstract description 16
- 239000000412 dendrimer Substances 0.000 claims abstract description 14
- 229920000736 dendritic polymer Polymers 0.000 claims abstract description 14
- 239000002202 Polyethylene glycol Substances 0.000 claims abstract description 9
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 9
- 229920001223 polyethylene glycol Polymers 0.000 claims abstract description 9
- WIEAVXXOSBZYEM-UHFFFAOYSA-N 1-hydroxypyrrolidine-2,5-dione;2-[4,7,10-tris(carboxymethyl)-1,4,7,10-tetrazacyclododec-1-yl]acetic acid Chemical compound ON1C(=O)CCC1=O.OC(=O)CN1CCN(CC(O)=O)CCN(CC(O)=O)CCN(CC(O)=O)CC1 WIEAVXXOSBZYEM-UHFFFAOYSA-N 0.000 claims abstract description 7
- 239000002253 acid Substances 0.000 claims abstract description 7
- 238000004108 freeze drying Methods 0.000 claims abstract description 7
- 239000000047 product Substances 0.000 claims abstract description 7
- 238000003756 stirring Methods 0.000 claims description 27
- 239000012528 membrane Substances 0.000 claims description 14
- 230000004913 activation Effects 0.000 claims description 13
- 238000000502 dialysis Methods 0.000 claims description 12
- 101000934372 Homo sapiens Macrosialin Proteins 0.000 claims description 9
- 102100025136 Macrosialin Human genes 0.000 claims description 9
- 238000000034 method Methods 0.000 claims description 7
- 239000012153 distilled water Substances 0.000 claims description 6
- 238000002156 mixing Methods 0.000 claims description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 6
- 210000001258 synovial membrane Anatomy 0.000 claims description 4
- 239000003153 chemical reaction reagent Substances 0.000 claims description 2
- 239000008363 phosphate buffer Substances 0.000 claims description 2
- 239000012279 sodium borohydride Substances 0.000 claims 1
- 229910000033 sodium borohydride Inorganic materials 0.000 claims 1
- 230000003472 neutralizing effect Effects 0.000 abstract 1
- 239000000243 solution Substances 0.000 description 77
- 206010061218 Inflammation Diseases 0.000 description 4
- 230000004054 inflammatory process Effects 0.000 description 4
- 210000002540 macrophage Anatomy 0.000 description 4
- 239000008055 phosphate buffer solution Substances 0.000 description 4
- 210000003131 sacroiliac joint Anatomy 0.000 description 4
- 241001111421 Pannus Species 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 230000003628 erosive effect Effects 0.000 description 2
- 230000008595 infiltration Effects 0.000 description 2
- 238000001764 infiltration Methods 0.000 description 2
- 108091005703 transmembrane proteins Proteins 0.000 description 2
- 102000035160 transmembrane proteins Human genes 0.000 description 2
- LOGFVTREOLYCPF-KXNHARMFSA-N (2s,3r)-2-[[(2r)-1-[(2s)-2,6-diaminohexanoyl]pyrrolidine-2-carbonyl]amino]-3-hydroxybutanoic acid Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@H]1CCCN1C(=O)[C@@H](N)CCCCN LOGFVTREOLYCPF-KXNHARMFSA-N 0.000 description 1
- 102100021943 C-C motif chemokine 2 Human genes 0.000 description 1
- 101710155857 C-C motif chemokine 2 Proteins 0.000 description 1
- 102000019034 Chemokines Human genes 0.000 description 1
- 108010012236 Chemokines Proteins 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 102000003777 Interleukin-1 beta Human genes 0.000 description 1
- 108090000193 Interleukin-1 beta Proteins 0.000 description 1
- 108010065637 Interleukin-23 Proteins 0.000 description 1
- 102000013264 Interleukin-23 Human genes 0.000 description 1
- 108090001005 Interleukin-6 Proteins 0.000 description 1
- 102000004889 Interleukin-6 Human genes 0.000 description 1
- 102000002274 Matrix Metalloproteinases Human genes 0.000 description 1
- 108010000684 Matrix Metalloproteinases Proteins 0.000 description 1
- 102100029438 Nitric oxide synthase, inducible Human genes 0.000 description 1
- 101710089543 Nitric oxide synthase, inducible Proteins 0.000 description 1
- 208000029082 Pelvic Inflammatory Disease Diseases 0.000 description 1
- 102100038280 Prostaglandin G/H synthase 2 Human genes 0.000 description 1
- 108050003267 Prostaglandin G/H synthase 2 Proteins 0.000 description 1
- 206010049677 Salpingo-oophoritis Diseases 0.000 description 1
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 1
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 1
- 230000002146 bilateral effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 210000002808 connective tissue Anatomy 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 230000035194 endochondral ossification Effects 0.000 description 1
- 238000003364 immunohistochemistry Methods 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 230000028709 inflammatory response Effects 0.000 description 1
- 229940124829 interleukin-23 Drugs 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 230000004807 localization Effects 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000011164 ossification Effects 0.000 description 1
- 231100000915 pathological change Toxicity 0.000 description 1
- 230000036285 pathological change Effects 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 210000004180 plasmocyte Anatomy 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 230000000770 proinflammatory effect Effects 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 210000005222 synovial tissue Anatomy 0.000 description 1
- 210000002437 synoviocyte Anatomy 0.000 description 1
- 201000004595 synovitis Diseases 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 230000008719 thickening Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G81/00—Macromolecular compounds obtained by interreacting polymers in the absence of monomers, e.g. block polymers
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G83/00—Macromolecular compounds not provided for in groups C08G2/00 - C08G81/00
- C08G83/002—Dendritic macromolecules
- C08G83/003—Dendrimers
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
- G01N33/6893—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids related to diseases not provided for elsewhere
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2800/00—Detection or diagnosis of diseases
- G01N2800/10—Musculoskeletal or connective tissue disorders
- G01N2800/101—Diffuse connective tissue disease, e.g. Sjögren, Wegener's granulomatosis
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- Urology & Nephrology (AREA)
- Biomedical Technology (AREA)
- Medicinal Chemistry (AREA)
- Hematology (AREA)
- Molecular Biology (AREA)
- Food Science & Technology (AREA)
- Pathology (AREA)
- Cell Biology (AREA)
- Biotechnology (AREA)
- Physics & Mathematics (AREA)
- Analytical Chemistry (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- General Physics & Mathematics (AREA)
- Microbiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Polymers & Plastics (AREA)
- Organic Chemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Other Resins Obtained By Reactions Not Involving Carbon-To-Carbon Unsaturated Bonds (AREA)
- Polyethers (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention discloses a gadolinium ion-polyethylene glycol-dendrimer-CD 68 antibody polymer, the structural formula is shown in formula I, and the preparation method of the polymer comprises the following steps: reacting dimethyl sulfoxide solution with 1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid-N-hydroxysuccinimide ester to obtain dendrimer solution; neutralizing the dendrimer solution with a CD68-PEG-COOH and dimethyl sulfoxide solution, and reacting to obtain a solution a; adding carboxylated polyethylene glycol into the solution a to obtain a solution b; adding a chloroauric acid solution into the solution b to obtain a solution c; adding NaBH to solution c4Obtaining a solution d; adding triethylamine into the solution d, and then adding acetic anhydride to obtainA reaction product; dialyzing the reaction product, and freeze-drying the dialyzed product to obtain polymer Gd-PEG-G5.0-CD68 antibody polymer.
Description
Technical Field
The invention relates to the technical field of biology, in particular to a preparation method of a gadolinium ion-polyethylene glycol-dendrimer-CD 68 antibody polymer.
Background
AS lesions almost entirely affect the bilateral sacroiliac joints (SIJ). Previous studies have considered the underlying pathological feature of SIJ adnexitis. With the inflammation erosion of the attachment points, new bone formation and nonspecific endochondral ossification in the inflammation repair process are caused, and finally joint rigidity is caused. The pathological changes of early SIJ inflammation are mainly characterized by synovitis, which is mainly characterized by thickening of a synovial lining cell layer, infiltration of a small amount of lymphocytes, plasma cells and a large amount of macrophages in loose connective tissues and formation of pannus.
In a healthy state, macrophages
Is one of the important resident cell types in the synovial tissue of joints. When the inflammation of the joint occurs, the joint is,
the sub-lining layer and lining layer at the cartilaginous surface-pannus junction are activated and proliferate rapidly, reaching 30% -40% of the cell content. And stationary
Compared with, activated
The CD68 receptor is a highly glycosylated transmembrane protein of 87-115kDa, which is found in the CD68 receptor, a highly glycosylated transmembrane protein of 87-115kDa, and which produces large amounts of proinflammatory cytokines (e.g., tumor necrosis factor- α, IL-6, interleukin-1 β, interleukin-23), chemokines (e.g., MCP-1), and enzymes (COX-2, iNOS, and MMPs) to drive inflammatory responses and joint destruction
Is highly specifically expressed on the surface of (1). The CD68 receptor is among the candidate receptors responsible for uptake of oxidized LDL
Increased after activation, and synovial membrane
The erosive nature of (a), the invasive activity within the pannus and the activity of the disease are closely related to the expression of CD 68. Thus, targeting the CD68 receptor is an effective method for detecting synovial macrophages.
However, in the prior art, the CD68 receptor is detected mainly by obtaining a local specimen by invasive means and then performing immunohistochemistry in vitro, and the CD68 receptor cannot be detected in the synovial membrane
Soak in the image, and fail to align the slip film
And (6) positioning.
Therefore, a technical problem to be solved by those skilled in the art is to provide a compound which can detect CD68 receptor and can realize the localization of macrophages in synovium.
Disclosure of Invention
In view of the above, the present invention provides a gadolinium ion-polyethylene glycol-dendrimer-CD 68 antibody polymer, which makes it possible to visualize macrophage infiltration images in synovium.
In order to achieve the purpose, the invention adopts the following technical scheme:
a preparation method of gadolinium ion-polyethylene glycol-dendrimer-CD 68 antibody polymer comprises the following steps:
1) adding 1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid-N-hydroxysuccinimide ester into a container filled with dimethyl sulfoxide solution while stirring, and reacting for 20-25h to obtain a dendrimer solution;
2) dissolving CD68-PEG-COOH in dimethyl sulfoxide solution, then dropwise adding the dendrimer solution, and reacting for 64-76h to obtain solution a;
3) adding carboxylated polyethylene glycol into the solution a, and reacting for 64-78h to obtain a solution b;
4) adding a chloroauric acid solution into the solution b, and stirring and reacting at room temperature for 25-35min to obtain a solution c;
5) adding NaBH to the solution c4Stirring the solution at room temperature for 1-4h, and then dropwise adding Gd (NO)3)3The solution reacts for 20 to 26 hours to obtain solution d;
6) adding triethylamine into the solution d, stirring and mixing for 22-32min, then adding acetic anhydride, stirring and reacting for 18-28h at room temperature to obtain a reaction product;
7) dialyzing the reaction product, and freeze-drying the dialyzed product to obtain polymer Gd-PEG-G5.0-CD68 antibody polymer.
In the preferred embodiment of the present invention, in step 2), CD68-PEG-COOH is dissolved in dimethylsulfoxide solution, and then EDC is added for activation.
As a preferred technical scheme of the invention, in the step 3), after adding the carboxylated polyethylene glycol, EDC is added for activation.
As a preferred embodiment of the present invention, in step 7), the reaction product is dialyzed against a dialysis membrane in a phosphate buffer and distilled water.
As a preferred technical scheme of the invention, the dialysis membrane is MWCO 10000.
The gadolinium ion-polyethylene glycol-dendrimer-CD 68 antibody polymer prepared by the preparation method is applied to preparation of a reagent for detecting CD68 receptors in synovium.
Detailed Description
The technical solutions in the embodiments of the present invention are clearly and completely described below, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
Example 1
A preparation method of gadolinium ion-polyethylene glycol-dendrimer-CD 68 antibody polymer comprises the following steps:
step one, adding 1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid-N-hydroxysuccinimide ester into a container filled with dimethyl sulfoxide solution while stirring, and reacting for 20 hours to obtain a dendrimer solution;
dissolving CD68-PEG-COOH in dimethyl sulfoxide solution, then dropwise adding the dendrimer solution, adding EDC for activation, and reacting for 64h to obtain solution a;
step three, adding carboxylated polyethylene glycol into the solution a, adding EDC for activation, and reacting for 64 hours to obtain a solution b;
step four, adding a chloroauric acid solution into the solution b, and stirring and reacting for 25min at room temperature to obtain a solution c;
step five, adding NaBH into the solution c4The solution is stirred and reacted for 1h at room temperature, and then Gd (NO) is added dropwise3)3Reacting the solution for 20 hours to obtain a solution d;
sixthly, adding triethylamine into the solution d, stirring and mixing for 22min, then adding acetic anhydride, stirring and reacting for 18h at room temperature to obtain a reaction product;
and seventhly, dialyzing the reaction product in phosphate buffer solution and distilled water by using a dialysis membrane, wherein the dialysis membrane is MWCO10000, and freeze-drying the dialyzed product to obtain a polymer Gd-PEG-G5.0-CD68 antibody polymer.
Example 2
A preparation method of gadolinium ion-polyethylene glycol-dendrimer-CD 68 antibody polymer comprises the following steps:
step one, adding 1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid-N-hydroxysuccinimide ester into a container filled with dimethyl sulfoxide solution while stirring, and reacting for 25 hours to obtain a dendrimer solution;
dissolving CD68-PEG-COOH in dimethyl sulfoxide solution, then dropwise adding the dendrimer solution, adding EDC for activation, and reacting for 76h to obtain solution a;
step three, adding carboxylated polyethylene glycol into the solution a, adding EDC for activation, and reacting for 78 hours to obtain a solution b;
step four, adding a chloroauric acid solution into the solution b, and stirring and reacting for 35min at room temperature to obtain a solution c;
step five, adding NaBH into the solution c4The solution is stirred and reacted for 4h at room temperature, and then Gd (NO) is added dropwise3)3Reacting the solution for 26 hours to obtain a solution d;
sixthly, adding triethylamine into the solution d, stirring and mixing for 32min, then adding acetic anhydride, stirring and reacting for 18-28h at room temperature to obtain a reaction product;
and seventhly, dialyzing the reaction product in phosphate buffer solution and distilled water by using a dialysis membrane, wherein the dialysis membrane is MWCO10000, and freeze-drying the dialyzed product to obtain a polymer Gd-PEG-G5.0-CD68 antibody polymer.
Example 3
A preparation method of gadolinium ion-polyethylene glycol-dendrimer-CD 68 antibody polymer comprises the following steps:
step one, adding 1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid-N-hydroxysuccinimide ester into a container filled with dimethyl sulfoxide solution while stirring, and reacting for 22 hours to obtain a dendrimer solution;
dissolving CD68-PEG-COOH in dimethyl sulfoxide solution, then dropwise adding the dendrimer solution, adding EDC for activation, and reacting for 70h to obtain solution a;
step three, adding carboxylated polyethylene glycol into the solution a, adding EDC for activation, and reacting for 70 hours to obtain a solution b;
step four, adding a chloroauric acid solution into the solution b, and stirring and reacting for 30min at room temperature to obtain a solution c;
step five, adding NaBH into the solution c4The solution is stirred and reacted for 3h at room temperature, and then Gd (NO) is added dropwise3)3Reacting the solution for 22 hours to obtain a solution d;
sixthly, adding triethylamine into the solution d, stirring and mixing for 25min, then adding acetic anhydride, and stirring and reacting for 25h at room temperature to obtain a reaction product;
and seventhly, dialyzing the reaction product in phosphate buffer solution and distilled water by using a dialysis membrane, wherein the dialysis membrane is MWCO10000, and freeze-drying the dialyzed product to obtain a polymer Gd-PEG-G5.0-CD68 antibody polymer.
Example 4
A preparation method of gadolinium ion-polyethylene glycol-dendrimer-CD 68 antibody polymer comprises the following steps:
step one, adding 1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid-N-hydroxysuccinimide ester into a container filled with dimethyl sulfoxide solution while stirring, and reacting for 23 hours to obtain a dendrimer solution;
dissolving CD68-PEG-COOH in dimethyl sulfoxide solution, then dropwise adding the dendrimer solution, adding EDC for activation, and reacting for 72h to obtain solution a;
step three, adding carboxylated polyethylene glycol into the solution a, adding EDC for activation, and reacting for 68 hours to obtain a solution b;
step four, adding a chloroauric acid solution into the solution b, and stirring and reacting for 28min at room temperature to obtain a solution c;
step five, adding NaBH into the solution c4The solution is stirred and reacted for 2h at room temperature, and then Gd (NO) is added dropwise3)3Reacting the solution for 24 hours to obtain a solution d;
sixthly, adding triethylamine into the solution d, stirring and mixing for 27min, then adding acetic anhydride, and stirring and reacting for 22h at room temperature to obtain a reaction product;
and seventhly, dialyzing the reaction product in phosphate buffer solution and distilled water by using a dialysis membrane, wherein the dialysis membrane is MWCO10000, and freeze-drying the dialyzed product to obtain a polymer Gd-PEG-G5.0-CD68 antibody polymer.
The embodiments in the present description are described in a progressive manner, each embodiment focuses on differences from other embodiments, and the same and similar parts among the embodiments are referred to each other. The device disclosed by the embodiment corresponds to the method disclosed by the embodiment, so that the description is simple, and the relevant points can be referred to the method part for description.
The previous description of the disclosed embodiments is provided to enable any person skilled in the art to make or use the present invention. Various modifications to these embodiments will be readily apparent to those skilled in the art, and the generic principles defined herein may be applied to other embodiments without departing from the spirit or scope of the invention. Thus, the present invention is not intended to be limited to the embodiments shown herein but is to be accorded the widest scope consistent with the principles and novel features disclosed herein.
Claims (6)
1. A preparation method of gadolinium ion-polyethylene glycol-dendrimer-CD 68 antibody polymer is characterized by comprising the following steps:
1) under the condition of stirring, adding 1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid-N-hydroxysuccinimide ester into the dimethyl sulfoxide solution, and reacting for 20-25h to obtain a dendrimer solution;
2) dissolving CD68-PEG-COOH in dimethyl sulfoxide solution, then dropwise adding the dendrimer solution, and reacting for 64-76h to obtain solution a;
3) adding carboxylated polyethylene glycol into the solution a, and stirring for reacting for 64-78h to obtain a solution b;
4) adding a chloroauric acid solution into the solution b, and stirring and reacting at room temperature for 25-35min to obtain a solution c;
5) adding NaBH4 solution into the solution c, stirring the solution at room temperature for reaction for 1 to 4 hours, and then dropwise adding Gd (NO)3)3The solution reacts for 20 to 26 hours to obtain solution d;
6) adding triethylamine into the solution d, stirring and mixing for 22-32min, then adding acetic anhydride, stirring and reacting for 18-28h at room temperature to obtain a reaction product;
7) dialyzing the reaction product, and freeze-drying the dialyzed product to obtain polymer Gd-PEG-G5.0-CD68 antibody polymer.
2. The method for preparing gadolinium ion-polyethylene glycol-dendrimer-CD 68 antibody polymer according to claim 1, wherein in step 2), CD68-PEG-COOH is dissolved in dimethyl sulfoxide solution, and EDC is added for activation.
3. The method for preparing gadolinium ion-polyethylene glycol-dendrimer-CD 68 antibody polymer according to claim 2, wherein EDC is added for activation after the carboxylated polyethylene glycol is added in step 3).
4. The method for preparing gadolinium ion-polyethylene glycol-dendrimer-CD 68 antibody polymer according to claim 3, wherein in step 7), the reaction product is dialyzed with a dialysis membrane in phosphate buffer and distilled water.
5. The method for preparing gadolinium ion-polyethylene glycol-dendrimer-CD 68 antibody polymer according to claim 4, wherein the dialysis membrane is MWCO 10000.
6. The use of gadolinium ion-polyethylene glycol-dendrimer-CD 68 antibody polymer prepared according to the preparation method of any one of claims 2 to 5 in the preparation of a reagent for detecting CD68 receptors in synovium.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010525997.8A CN111763326A (en) | 2020-06-10 | 2020-06-10 | Gadolinium ion-polyethylene glycol-dendrimer-CD 68 antibody polymer and preparation method and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010525997.8A CN111763326A (en) | 2020-06-10 | 2020-06-10 | Gadolinium ion-polyethylene glycol-dendrimer-CD 68 antibody polymer and preparation method and application thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN111763326A true CN111763326A (en) | 2020-10-13 |
Family
ID=72720504
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202010525997.8A Pending CN111763326A (en) | 2020-06-10 | 2020-06-10 | Gadolinium ion-polyethylene glycol-dendrimer-CD 68 antibody polymer and preparation method and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN111763326A (en) |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103877597A (en) * | 2014-03-19 | 2014-06-25 | 中国人民解放军第二军医大学 | Pegylated polyethyleneimine macromolecular magnetic resonance imaging contrast agent and preparation method of contrast agent |
| CN109602920A (en) * | 2019-01-18 | 2019-04-12 | 厦门大学 | A kind of high stability novel dendritic molecular image probe and preparation method thereof |
-
2020
- 2020-06-10 CN CN202010525997.8A patent/CN111763326A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103877597A (en) * | 2014-03-19 | 2014-06-25 | 中国人民解放军第二军医大学 | Pegylated polyethyleneimine macromolecular magnetic resonance imaging contrast agent and preparation method of contrast agent |
| CN109602920A (en) * | 2019-01-18 | 2019-04-12 | 厦门大学 | A kind of high stability novel dendritic molecular image probe and preparation method thereof |
Non-Patent Citations (3)
| Title |
|---|
| JINGWEN CHEN ET AL.: ""Multifunctional gold nanocomposites designed for targeted CT/MR/optical trimodal imaging of human non-small cell lung cancer cells"", 《NANOSCALE》 * |
| LIU JY ET AL.: ""Zwitterionic Gadolinium(III)-Complexed Dendrimer-Entrapped Gold Nanoparticles for Enhanced Computed Tomography/Magnetic Resonance Imaging of Lung Cancer Metastasis"", 《ACS APPLIED MATERIALS & INTERFACES》 * |
| ZHU JY ET AL.: ""Encapsulation of doxorubicin within multifunctional gadolinium-loaded dendrimer nanocomplexes for targeted theranostics of cancer cells"", 《RSC ADVANCES》 * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN103030801B (en) | Segmented degradable polymers and conjugates made therefrom | |
| CN101541347B (en) | Drug carriers, their synthesis, and methods of use thereof | |
| US5043326A (en) | Inclusion complex of 7-isopropoxy-isoflavon formed with cyclodextrin, the preparation thereof and pharmaceutical compositions containing these compounds as active ingredients | |
| TW200808359A (en) | Functionalized poly(ethylene glycol) | |
| CN112409384B (en) | Double thiophene thiadiazole receptor near-infrared two-region fluorescent molecule and preparation method and application thereof | |
| Dong et al. | Amphiphilic hydroxyalkyl cellulose derivatives for amorphous solid dispersion prepared by olefin cross-metathesis | |
| JP2002506087A (en) | Poly (ethylene glycol) derivatives with proximal reactive groups | |
| JPH08507549A (en) | Water-soluble non-immunogenic polyamide crosslinker | |
| CN101243053A (en) | N-acylic aminoacid derivatives, method for the production thereof, pharmacological composition and the use in the form of anti-allergic, anti-inflammatory and hypolipidemic agents | |
| JP2009523191A (en) | Highly efficient production of polyalkylene oxide carboxylic acid | |
| CN111763326A (en) | Gadolinium ion-polyethylene glycol-dendrimer-CD 68 antibody polymer and preparation method and application thereof | |
| US20180044280A1 (en) | Y-type discrete polyethylene glycol derivative and preparation method thereof | |
| EP0354836B1 (en) | Iodopolymers with a dextran skeleton, their processes of preparation and their applications as contrast agents | |
| Bencini et al. | Poly (4‐acryloylmorpholine) oligomers carrying a β‐cyclodextrin residue at one terminus | |
| JPS6392647A (en) | Novel thyronine derivative | |
| CN102964588A (en) | Preparation method and application of acid or active ester of polyethylene glycol with tail end connected with aminophenyl propionic acid | |
| Yang et al. | Simplified one-pot 18F-labeling of biomolecules with in situ generated fluorothiophosphate synthons in high molar activity | |
| EP0689844A1 (en) | Complexes of vinpocetine formed with cyclodextrins, process for their preparation and pharmaceutical compositions containing them | |
| CN105233810A (en) | Bionic double-chain phospholipid film monolithic column, and making method and application thereof | |
| JP2018508632A (en) | Process for fractionating esterified cellulose ethers | |
| CN103613754A (en) | Biocompatible thermosensitive poly-N-acetyl-glutamic acid/lysine methyl ester and preparation method thereof | |
| WO2022255479A1 (en) | Medium-sized molecule compound conjugated body for improving blood kinetics of medium-sized molecule compound and method for producing same | |
| Haneef et al. | Implication of Differential Surface Anisotropy on Biopharmaceutical Performance of Polymorphic Forms of Ambrisentan | |
| US20200368373A1 (en) | Optical imaging agents targeting inflammation | |
| TWI793782B (en) | Method of sugar-guided modifying glycosylated polypeptide and application of the same |
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 | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20201013 |
|
| RJ01 | Rejection of invention patent application after publication |