CN110862546B - Methotrexate metal coordination polymer and preparation method and application thereof - Google Patents
Methotrexate metal coordination polymer and preparation method and application thereof Download PDFInfo
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- CN110862546B CN110862546B CN201910970581.4A CN201910970581A CN110862546B CN 110862546 B CN110862546 B CN 110862546B CN 201910970581 A CN201910970581 A CN 201910970581A CN 110862546 B CN110862546 B CN 110862546B
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- A61K49/00—Preparations for testing in vivo
- A61K49/06—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations
- A61K49/08—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by the carrier
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
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Abstract
The invention discloses a methotrexate metal coordination polymer and a preparation method and application thereof, and the structural formula is as follows:
wherein R is functional metal ion. The invention introduces Gd capable of being imaged by MRI into the structure of MTXIIIAnd FeIIIObtaining MTX-GdIIIAnd MTX-FeIIIThe coordination polymer can be efficiently delivered to folate receptor over-expressed tumor cells under the mediation of active targeting (MTX has strong affinity with folate receptor), so that the administration dosage is reduced, and accurate and efficient diagnosis and treatment of tumor lesions are realized; by introducing Zn with immune promoting effect into the structure of MTXIIObtaining MTX-ZnIICoordination polymers, which are expected to be highly effective in treating tumors and immune diseases.
Description
Technical Field
The invention belongs to the technical field of coordination chemistry, and particularly relates to a methotrexate metal coordination polymer and a preparation method and application thereof.
Background
Coordination chemistry is the interaction of metal atoms or ions with organic and inorganic ions and the formation of coordination complexes by coordinative bonding. With the progress of research on life sciences and diseases, it is found that many life phenomena include interactions between metal ions. In addition, designing new diagnostic agents based on coordination chemistry is also a major strategy to combat serious diseases. Therefore, in recent years, coordination chemistry has been widely used in the biomedical field. Some organic molecules and metals with diagnosis and treatment effects cannot be directly applied to clinic due to the defects of poor curative effect, large toxic and side effects, difficult absorption and the like, but if the organic molecules and the metals are modified into coordination compounds, the curative effect is expected to be improved, and the toxic and side effects are reduced. For example, various chelates of gadolinium (Gd) have extremely low toxic side effects and are widely used as Magnetic Resonance Imaging (MRI) contrast agents in clinical practice; the ferric citrate complex can be used for treating iron deficiency anemia; the copper coordination compound of aspirin and salicylic acid derivatives can greatly improve the anti-rheumatism effect; bleomycin has no tumor affinity, and the activity of a coordination compound formed by bleomycin and cobalt ions is greatly improved; the cis-palladium-platinum coordination compound has excellent anti-tumor effect; many ligands selectively form water-soluble chelates with harmful metals and metal ions, which are excreted via the kidney for detoxification. The above examples fully demonstrate that the development of novel biological diagnostic and therapeutic agents based on coordination chemistry design has great development prospects, and can be better applied to the field of biological medicine.
MTX (CAS number: 59-05-2) is a folic acid antimetabolite, can combine with folate receptors on the surfaces of tumor cells to play a good targeting role, and is commonly used for treating various malignant tumors. In addition, MTX is also one of the optional medicines for treating acute leukemia and autoimmune diseases. However, MTX still has many disadvantages in clinical application, such as difficulty in crossing the Blood Brain Barrier (BBB) in treating brain tumors. The medicine can increase the toxicity of liver and kidney functions, and has toxicity to normal biological cells because the medicine action mechanism is to inhibit the synthesis of tumor cell DNA by inhibiting dihydrofolate reductase. Researches find that the MTX prodrug modified by the amphiphilic polymer material has the advantages of improving the targeting property and bioavailability of the medicament, reducing the toxic and side effects of the medicament and the like. More importantly, the nano-drug formed by self-assembly enters into the body, and the phagocytosis of the RES system of the human body can be effectively reduced. The nano-drug system can control the drug release when reaching the target position, reduce the drug dosage, enhance the drug efficacy and reduce the drug toxicity. Meanwhile, the nano-drug system can avoid the loss of the activity of the drug and is beneficial to the storage and delivery of the drug. Virtually all nano-drug modified dosage forms also introduce undefined systemic toxicity in conjunction with the introduction of the carrier. In order to solve the problem, a carrier-free amphiphilic nano diagnosis and treatment system constructed by hydrophilic and hydrophobic diagnosis and treatment agents through methods such as chemical bonding, physical interaction force, metal coordination and the like is also concerned at present, but the stability of the nano diagnosis and treatment system is poorer than that of the traditional carrier-carrying nano diagnosis and treatment system.
Disclosure of Invention
The invention aims to overcome the defects of the prior art and provide a methotrexate metal coordination polymer.
Another object of the present invention is to provide a method for preparing the above-mentioned methotrexate metal complex polymer.
Still another object of the present invention is to provide the use of the above-mentioned methotrexate metal complex polymer.
The technical scheme of the invention is as follows:
the methotrexate metal coordination polymer has a structural formula as follows:
In a preferred embodiment of the invention, R is GdIII、FeIIIOr ZnII。
The other technical scheme of the invention is as follows:
a preparation method of methotrexate metal coordination polymer comprises the following steps:
(1) mixing MTX and metal salt containing functional metal ions in a weak alkaline solution for reaction to obtain MTX metal coordination polymer mixed solution;
(2) removing impurities in the MTX metal coordination polymer mixed solution, and freeze-drying to obtain the methotrexate metal coordination polymer.
In a preferred embodiment of the present invention, the functional metal ion is GdIII、FeIIIOr ZnII。
Further preferably, the metal salt is gadolinium chloride hexahydrate (GdCl)3·6H2O, CAS number: 13450-84-5), ferric chloride hexahydrate (FeCl)3·6H2O, CAS number: 10025-77-1) or zinc chloride (ZnCl)2CAS number: 7646-85-7).
The invention adopts another technical scheme as follows:
the methotrexate metal coordination polymer is applied to the preparation of tumor targeted diagnosis and treatment medicines.
In a preferred embodiment of the present invention, the functional metal ion is GdIIIOr FeIII。
The methotrexate metal coordination polymer is applied to the preparation of immune disease treatment drugs.
In a preferred embodiment of the present invention, the functional metal ion is ZnII。
The invention has the beneficial effects that:
1. the invention introduces Gd capable of being imaged by MRI into the structure of MTXIIIAnd FeIIIObtaining MTX-GdIIIAnd MTX-FeIIIThe coordination polymer can be efficiently delivered to folate receptor over-expressed tumor cells under the mediation of active targeting (MTX has strong affinity with folate receptor), so that the administration dosage is reduced, and accurate and efficient diagnosis and treatment of tumor lesions are realized; by introducing Zn with immune promoting effect into the structure of MTXIIObtaining MTX-ZnIICoordination polymers, which are expected to be highly effective in treating tumors and immune diseases.
2. The synthesis process is extremely simple and easy to operate, the obtained product has excellent water solubility, other hydrophobic diagnosis and treatment agents can be efficiently loaded, a long-circulating self-assembly nano diagnosis and treatment system with good stability is easily prepared by a self-assembly technology, and the system can be efficiently delivered to the focus of tumor under the dual mediation of active targeting and passive targeting (tumor penetration and retention enhancement effect).
3. Experimental results prove that the MTX-Gd related to the inventionIIIAnd MTX-FeIIIThe coordination polymer has good tumor targeted diagnosis and treatment effects, particularly good relaxation enhancement capability when being used as an MRI contrast agent, can identify the tumor cells with over-expressed folate receptors with high selectivity, not only has strong targeted contrast effect, but also prolongs the imaging time of the contrast agent in vivo, thereby reducing the addition amount of the contrast agent and having strong practicability.
Drawings
FIG. 1 shows MTX and MTX-Gd prepared in example 1 of the present inventionIIIInfrared spectrum of coordination polymer.
FIG. 2 shows MTX-Gd prepared according to example 1 of the present inventionIIITransmission electron microscopy of coordination polymer.
FIG. 3 shows MTX and MTX-Fe obtained in example 2 of the present inventionIIIInfrared spectrum of coordination polymer.
FIG. 4 shows MTX-Fe obtained in example 2 of the present inventionIIITransmission electron microscopy of coordination polymer.
FIG. 5 shows MTX and MTX-Zn prepared in example 3 of the present inventionIIInfrared spectrum of coordination polymer.
FIG. 6 shows MTX-Zn prepared in example 3 of the present inventionIITransmission electron microscopy of coordination polymers.
FIG. 7 shows MTX-Gd prepared according to example 1 of the present inventionIIILongitudinal relaxation of coordination polymers (inset: T1 weighted MRI picture).
FIG. 8 shows MTX-Fe obtained in example 2 of the present inventionIIITransverse relaxation of coordination polymers (inset: T2 weighted MRI picture).
FIG. 9 shows MTX-Gd prepared according to example 1 of the present inventionIIITumor targeting MRI experiments and result graphs of coordination polymers after BALB/C nude mice intravenous injection.
FIG. 10 shows MTX-Fe obtained in example 2 of the present inventionIIICoordination polymer in BALB/C bareTumor targeted MRI experiments and results after intravenous injection in mice.
Detailed Description
The technical solution of the present invention is further illustrated and described by the following detailed description.
The most key concept of the invention is as follows: MTX and GdIII、FeIII、ZnIISeparately chelate-synthesizing MTX-Gd by coordination reactionIII、MTX-FeIII、MTX-ZnIIThree metal coordination polymers.
Referring to FIGS. 1 to 10, the present invention provides MTX-GdIII、MTX-FeIII、MTX-ZnIIThree coordination polymers having the following reaction formula:
the principle of the invention is as follows: MTX is taken as an aptamer (carboxyl and amino can give out lone pair electrons) and GdIII、FeIII、ZnII(easy to accept lone pair electrons) metal ions are synthesized into MTX-Gd through coordination reactionIII、MTX-FeIII、MTX-ZnIIThe three coordination polymers are used for diagnosing and treating tumors and immune diseases.
Example 1
(MTX-GdIIISynthesis of coordination polymer): 0.1mmol of MTX was completely dissolved in 15mL of ammonium acetate solution, and 0.2mmol of GdCl was added3·6H2Stirring O vigorously for 0.5h, adjusting pH of the reaction system to 8.5 with 0.2M sodium hydroxide, reacting at room temperature for 6h, terminating the reaction, and adding MTX-GdIIITransferring the crude product of the coordination polymer into a dialysis bag with the molecular weight cutoff of 1000Da for dialysis for 24h, and freeze-drying to obtain high-purity MTX-GdIIICoordination polymer (yield 40%). MTX-Gd synthesized by the methodIIIInfrared spectrum of coordination polymer (FIG. 1) illustrates GdIIICan be linked with MTX by coordination chemical bond, and the transmission electron microscopy picture (figure 2) shows that MTX-GdIIIThe coordination polymer may self-assemble to a diameter of about 100nmThe nanoparticles of (1).
Example 2
(MTX-FeIIISynthesis of coordination polymer): 0.1mmol of MTX was completely dissolved in 15mL of ammonium acetate solution, and 0.2mmol of GdCl was added3·6H2Stirring O vigorously for 0.5h, adjusting pH of the reaction system to 8.5 with 0.2M sodium hydroxide, reacting at room temperature for 12h, terminating the reaction, and adding MTX-FeIIITransferring the crude product of the coordination polymer into a dialysis bag with the molecular weight cutoff of 1000Da for dialysis for 24h, and freeze-drying to obtain high-purity MTX-FeIIICoordination polymer (yield 50%). MTX-Fe synthesized by the methodIIIInfrared spectrum of coordination polymer (FIG. 3) illustrates FeIIICan be linked with MTX by coordination chemical bond, and a transmission electron microscope picture (figure 4) shows that MTX-FeIIICoordination polymers can self-assemble into nanoparticles about 100nm in diameter.
Example 3
(MTX-ZnIISynthesis of coordination polymer): 0.1mmol of MTX was completely dissolved in 15mL of ammonium acetate solution, and 0.2mmol of ZnCl was added2·6H2Stirring O vigorously for 0.5h, adjusting pH of the reaction system to 8.5 with 0.2M sodium hydroxide, reacting at room temperature for 6h, terminating the reaction, and reacting MTX-ZnIITransferring the crude product of the coordination polymer into a dialysis bag with the molecular weight cutoff of 1000Da for dialysis for 24h, and freeze-drying to obtain high-purity MTX-ZnIICoordination polymer (yield 44%). MTX-Zn synthesized by the methodIIThe IR spectrum of the coordination polymer (FIG. 5) illustrates-ZnIICan be linked to MTX by coordination chemical bond, and the transmission electron microscopy (FIG. 6) shows that MTX-ZnIICoordination polymers can self-assemble into nanoparticles about 100nm in diameter.
Example 4
MTX-GdIIIAnd MTX-FeIIIIn vitro MRI imaging of coordination polymers: precisely weighing a certain amount of MTX-GdIIICoordination polymer, diluted to different Gd with PBS (pH7.4)IIIMTX-Gd concentrations (0.05, 0.1, 0.2, 0.4, 0.8mg/mL)IIIMixing the coordination polymer with 0.5% agar, transferring to a microcentrifuge tube, and collecting the mixture7TMRI scanner to test MTX-GdIIIT1-weighted MRI mapping and longitudinal relaxation of coordination polymers; ② accurately weighing a certain amount of MTX-FeIIICoordination polymer, diluted to different Fe with PBS (pH7.4)IIIMTX-Fe at concentrations (0.1, 0.2, 0.4, 0.8, 1.6mg/mL)IIIAfter coordination of the polymer, the mixture was mixed with 0.5% agar until homogeneous, transferred to a microcentrifuge tube and tested for MTX-Fe using a 7T MRI scannerIIIT2 weighted MRI images and transverse relaxations of coordination polymers. The above results are shown in FIGS. 7 and 8, respectively, and show MTX-GdIIIAnd MTX-FeIIIThe coordination polymer has good relaxation capacity and good contrast effect when being used as an MRI contrast agent.
MTX-GdIIIAnd MTX-FeIIIIn vivo MRI imaging of coordination polymers: BALB/C nude mice (age 5-6 weeks, 18. + -.2 g) were purchased from Shanghai laboratory animal research center. Axillary inoculation of nude mice with 1X 106HeLa cells, when the tumor volume grows to 100-3: firstly, to study MTX-GdIIIThe tumor targeting efficiency and T1 weighted MRI imaging performance of coordination polymer in animal body are realized by combining MTX-GdIIIInjecting the mixture into a nude mouse body through tail vein, and performing living body MRI real-time imaging by using a 7T MRI scanner at different specific time points respectively, wherein the result is shown in figure 9; ② to study MTX-FeIIIThe tumor targeting efficiency and T2 weighted MRI imaging performance of coordination polymer in animal body are realized by adding proper amount of MTX-FeIIIThe obtained product is injected into a nude mouse body through tail vein, and living MRI real-time imaging is carried out by using a 7T MRI scanner at different specific time points, and the result is shown in figure 10. The above results show that MTX-GdIIIAnd MTX-FeIIIThe two coordination polymers not only have strong targeting contrast effect, but also prolong the imaging time of the contrast agent in vivo.
In summary, the MTX coordination polymer, the synthesis method and the application thereof provided by the invention are characterized in that the MTX structure is matched with metal ion Gd capable of MRIIIIAnd FeIIIObtaining MTX-GdIIIAnd MTX-FeIIITwo coordination polymers realize the targeted diagnosis and treatment of tumors; by incorporating Zn which promotes human immunity into the structure of MTXIIObtaining MTX-ZnIIThe coordination polymer is expected to treat tumors and immune diseases with high efficiency. In a word, the metal coordination polymer can provide a new idea for the design of a nano drug carrier material with simple, flexible and intelligent design and the development of a novel targeted MRI contrast agent.
The above description is only a preferred embodiment of the present invention, and therefore should not be taken as limiting the scope of the invention, which is defined by the appended claims.
Claims (1)
1. The application of the methotrexate metal coordination polymer in the preparation of tumor targeted diagnosis and treatment medicines is characterized in that: the structural formula of the methotrexate metal coordination polymer is as follows:
The preparation method of the methotrexate metal coordination polymer comprises the following steps:
(1) mixing MTX and metal salt containing functional metal ions in a weak alkaline solution for reaction to obtain MTX metal coordination polymer mixed solution; the metal salt is gadolinium chloride hexahydrate or ferric chloride hexahydrate;
(2) removing impurities in the MTX metal coordination polymer mixed solution, and freeze-drying to obtain the methotrexate metal coordination polymer.
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Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105873569A (en) * | 2013-11-06 | 2016-08-17 | 芝加哥大学 | Nanoscale carriers for the delivery or co-delivery of chemotherapeutics, nucleic acids and photosensitizers |
| CN107001031A (en) * | 2014-10-14 | 2017-08-01 | 芝加哥大学 | Nano particle for photodynamic therapy, the photodynamic therapy of X ray induction, radiotherapy, chemotherapy, immunotherapy and its any combination |
| CN107007571A (en) * | 2017-02-24 | 2017-08-04 | 福州市传染病医院 | Coordinate self-assembly nanoparticle and the application altogether of the sensitive copper medicine of tumour subacidity |
| CN108014346A (en) * | 2018-01-29 | 2018-05-11 | 厦门大学 | A kind of preparation method of methotrexate (MTX) prodrug and its double targeted nano-particles |
| CN109310702A (en) * | 2016-05-20 | 2019-02-05 | 芝加哥大学 | Nano particle for chemotherapy, targeted therapies, photodynamic therapy, immunotherapy and any combination of them |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2009139939A2 (en) * | 2008-02-22 | 2009-11-19 | The University Of North Carolina At Chapel Hill | Hybrid nanoparticles as anti-cancer therapeutic agents and dual therapeutic/imaging contrast agents |
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Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105873569A (en) * | 2013-11-06 | 2016-08-17 | 芝加哥大学 | Nanoscale carriers for the delivery or co-delivery of chemotherapeutics, nucleic acids and photosensitizers |
| CN107001031A (en) * | 2014-10-14 | 2017-08-01 | 芝加哥大学 | Nano particle for photodynamic therapy, the photodynamic therapy of X ray induction, radiotherapy, chemotherapy, immunotherapy and its any combination |
| CN109310702A (en) * | 2016-05-20 | 2019-02-05 | 芝加哥大学 | Nano particle for chemotherapy, targeted therapies, photodynamic therapy, immunotherapy and any combination of them |
| CN107007571A (en) * | 2017-02-24 | 2017-08-04 | 福州市传染病医院 | Coordinate self-assembly nanoparticle and the application altogether of the sensitive copper medicine of tumour subacidity |
| CN108014346A (en) * | 2018-01-29 | 2018-05-11 | 厦门大学 | A kind of preparation method of methotrexate (MTX) prodrug and its double targeted nano-particles |
Non-Patent Citations (4)
| Title |
|---|
| Choi, Goeun等.Emerging nanomaterials with advanced drug delivery functions * |
| focused on methotrexate delivery.《COORDINATION CHEMISTRY REVIEWS》.2018,第359卷正文第32-51页. * |
| 稀有金属甲氨喋呤配合物与小牛胸腺DNA相互作用的研究;卢继新，等;《稀有金属》;20031130;第06卷(第27期);正文第747-750页， * |
| 若干3d过渡金属的甲氨喋呤配合物;陆小海，等;《应用化学》;19891031;第6卷(第5期);正文第11页，第12页最后两段 * |
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