Self-assembled complexes containing one or more of cobalt, silver, gadolinium, and iron

Abstract

To provide a self-assembled complex.SOLUTION: The present disclosure relates to a self-assembled complex composed of substances existing in a body and using the same as ligands, the self-assembled complex including: metal ions including one or more of cobalt (Co), silver (Ag), gadolinium (Gd), or iron (Fe); and one or more ligands that are self-assembled with the metal ions, wherein: the self-assembled complex is reversibly self-assembled or self-disassembled; self-assembly is performed by one or more of a concentration of the metal ions or a concentration of the ligand; and the form of the self-assembled complex is controlled depending on a combination of the ligands.SELECTED DRAWING: Figure 1

Description

[Technical Field]

[0001] The present invention relates to a self-assembly complex containing one or more of cobalt, silver, gadolinium, and iron, and more particularly to a self-assembly complex containing one or more of cobalt, silver, gadolinium, and iron that can control its shape and size by using substances present in the body as ligands and that is capable of substance transfer. [Background technology]

[0002] Recently, the global COVID-19 pandemic has sparked interest in antiviral and antibacterial technologies, leading to the development of antiviral and antibacterial technologies using metal ions. Silver and cobalt affect the metabolism of cells or viruses, causing cell death and virus destruction.

[0003] The main products and technologies involve applying metal ions to areas that people frequently come into contact with, and then releasing the metal ions to achieve antibacterial and antiviral effects.

[0004] Copper ions, which are primarily used for antibacterial and antiviral purposes, can cause toxicity in the human body, including hepatotoxicity, nephrotoxicity, anemia, immunotoxicity, and developmental toxicity, and their use can be fatal to infants, pregnant women, and the elderly and infirm. Therefore, it is necessary to replace them with other metals.

[0005] Cobalt ions are a rare example of a complex that is used in the body. They form a complex with a glyoxime ligand and have the physiological function of vitamin B12. This gives them a high potential for use in the body and low toxicity, but they have problems such as being difficult to apply to various substances and not easily forming complexes in the body.

[0006] In addition, there are products that use silver nanoparticles for antibacterial purposes, but the synthesis of silver ion nanoparticles is not cost competitive.

[0007] As the global population ages, the incidence of cancer increases as the human body ages, and as a result, the social costs associated with cancer increase, making it important to diagnose and treat cancer early. Therefore, active research into theragnosis, which allows for simultaneous diagnosis and treatment, is underway, and there is a growing need for materials that can diagnose and treat cancer at the same time.

[0008] The substances used in MRI-assisted theragnosis must have low toxicity in the body and be able to target cancer for effective treatment. Antigen-antibody reactions are typically used to specifically bind to cancer tissue, but this requires additional processing of the theragnosis substance or the addition of substances such as peptides or proteins, making it less cost-competitive and difficult to popularize.

[0009] Therefore, extensive research is being conducted on materials that can self-assemble with substances in the body, have high antibacterial properties but are non-toxic to the human body, and are low in production cost, as well as materials that can diagnose and treat various diseases as well as anti-cancer. Summary of the Invention [Problem to be solved by the invention]

[0010] An object of the present invention is to provide a self-assembly complex that is capable of self-assembly using substances present in the body.

[0011] Another object of the present invention is to provide a self-assembly complex that is non-toxic to the human body and whose shape and size can be controlled in a variety of ways.

[0012] Another object of the present invention is to provide a self-assembling composite containing one or more of cobalt, silver, gadolinium, and iron, which can self-assemble with substances in the body, has high antibacterial properties, and is low in production cost. [Means for solving the problem]

[0013] According to one aspect of the present invention, an embodiment of the present invention is a self-assembly complex that utilizes a substance present in the body as a ligand, and includes metal ions including at least one of cobalt (Co), silver (Ag), gadolinium (Gd), and iron (Fe); and at least one ligand that self-assembles with the metal ions; and the self-assembly or self-disassembly is reversibly carried out depending on at least one of the concentrations of the metal ions and the ligands, and the morphology of the self-assembly complex is controlled by the combination of the ligands.

[0014] In one embodiment, the metal ions may be cobalt ions, silver ions, gadolinium ions, or a gadolinium-iron ion mixture.

[0015] In one embodiment, the self-assembled complex may be self-disassembled by an external solution containing external ions.

[0016] In one embodiment, the self-assembly complex may be provided in a structure by aggregation of one or more of the metal ions and the ligand.

[0017] In one embodiment, the ligand may include one or more of a phosphate and a phosphonate.

[0018] In one embodiment, the ligand may include one or more of adenosine monophosphate, adenosine diphosphate, and adenosine triphosphate.

[0019] In one embodiment, the ligand includes one or more phosphates, and the self-assembly complex is formed by aggregating the ligand with one or more of the metal ions, and the structure is formed in a helical shape, and the size and number of helices in the structure can be controlled by the degree of mixing of the ligand with the number of phosphates.

[0020] In one embodiment, the ligand includes one or more phosphates, and the self-assembly complex is formed by aggregating one or more of the metal ions and the ligand to form a structure, and the structure has one or more of a helical, rod-like, and spherical shape, and the shape of the structure can be controlled by the degree of mixing of the ligand with the number of phosphates.

[0021] In one embodiment, the ligand includes one or more phosphates, and the self-assembly complex is formed by aggregating the ligand with one or more of the metal ions to form a structure, and the structure has a rod shape with an aspect ratio, and the aspect ratio of the structure can be controlled by the degree of mixing of the ligand with respect to the number of phosphates.

[0022] In one embodiment, the ligand includes one or more phosphates, and the self-assembly complex is provided in a structure by aggregating the ligand with one or more of the metal ions, and the degree of aggregation or size of the structure can be controlled by the degree of mixing of the ligand with respect to the number of the phosphates.

[0023] In one embodiment, the self-assembly complex further comprises an active ingredient therein, and the active ingredient may include any one or more of adenosine, guanosine, uridine, cytidine, and doxorubicin.

[0024] In one embodiment, the metal ions are any one of cobalt (Co), gadolinium (Gd), and iron (Fe), and the self-assembled complex may be paramagnetic.

[0025] In one embodiment, the metal ions are any one of cobalt (Co), gadolinium (Gd), and iron (Fe), and the self-assembled complex can move a first distance when an externally applied magnetic field is applied.

[0026] In one embodiment, the metal ion is any one of cobalt (Co), gadolinium (Gd), and iron (Fe), and the self-assembly complex is paramagnetic and its magnetic moment can be adjusted depending on the conditions under which it is formed.

[0027] In one embodiment, the metal ion and the ligand form a self-assembly complex through a coordinate bond, and adjacent ligands may be connected to each other through π-π interactions or hydrogen bonds.

[0028] In one embodiment, the metal ions are gadolinium (Gd) ions; or a mixture of gadolinium (Gd) and iron (Fe) ions. The self-assembly complex is provided by aggregation of the metal ions and the ligands into a structure, and the size of the structure can be controlled by the concentration of the ligands.

[0029] In one embodiment, the metal ions are gadolinium (Gd) ions; or a mixture of gadolinium (Gd) and iron (Fe) ions. The self-assembly complex is formed by aggregating the metal ions and the ligands into a structure, and the size of the structure can be controlled by the reaction time.

[0030] In one embodiment, the metal ion is gadolinium (Gd) ion; or a mixture of gadolinium (Gd) and iron (Fe) ions, and the self-assembly complex is loaded with a drug, such as doxorubicin or adenosine, which may exhibit a sustained release pattern over a desired period of time, enabling sustained release.

[0031] In one embodiment, the desired period may be selected from the range of 0.5 hours to 12 months.

[0032] In one embodiment, the release rate of the drug can be controlled by the size of the self-assembled complex. [Effects of the Invention]

[0033] According to the present invention described above, it is possible to provide a self-assembly complex that is capable of self-assembly using substances present in the body.

[0034] Furthermore, the present invention can provide a self-assembly complex that is non-toxic to the human body and whose shape and size can be controlled in a variety of ways. [Brief explanation of the drawings]

[0035] [Figure 1] 1 is a schematic diagram illustrating a self-assembly complex using cobalt metal ions and adenosine monophosphate or mixed adenosine phosphate ligands among the phosphate ligands in an embodiment of the present invention. [Figure 2] 1 is a diagram showing a helical self-assembly complex formed by the self-assembly of cobalt metal ions and adenosine monophosphate. [Figure 3] 1 is a diagram showing aspect ratio control of a self-assembly complex of cobalt metal ions and adenosine monophosphate and adenosine triphosphate mixed ligands. [Figure 4] 1 is a diagram showing the element ratio of a self-assembled complex of cobalt metal ions and adenosine monophosphate confirmed by a transmission electron microscope. [Figure 5] 1 is a diagram showing the movement of a self-assembly complex using cobalt metal ions and adenosine monophosphate when an external magnetic field is applied to the self-assembly complex in an embodiment of the present invention. [Figure 6] 1 is a schematic diagram illustrating a self-assembly complex using silver metal ions and adenosine monophosphate or mixed adenosine phosphate ligands among the phosphate ligands in an embodiment of the present invention. [Figure 7] 1 is a diagram illustrating the formation of a self-assembly complex between gadolinium ions and a ligand, the formation of a self-assembly complex between gadolinium and iron ions and a ligand, and mass transfer using the same, according to an embodiment of the present invention. [Figure 8] 1 is a diagram showing a self-assembled complex depending on the concentration of gadolinium ions and ligands according to an embodiment of the present invention. [Figure 9] 1 is a diagram showing the effect of quenching on self-assembled complexes of gadolinium and iron ions with ligands. [Figure 10] 1 is a diagram showing the movement of a self-assembled complex of gadolinium ions and a ligand, and a self-assembled complex of gadolinium and iron ions and a ligand when an external magnetic field is applied. DETAILED DESCRIPTION OF THE INVENTION

[0036] Other specific details of the embodiments are included in the detailed description and drawings.

[0037] The advantages and features of the present invention, as well as methods for achieving them, will become clearer with reference to the embodiments described below in detail with the accompanying drawings. However, the present invention is not limited to the embodiments disclosed below and may be embodied in a variety of different forms. Unless otherwise specified in the following description, all numbers, values, and / or expressions expressing components, reaction conditions, and component contents in the present invention are approximate values ​​that inherently reflect various uncertainties in measurement that arise in obtaining such values, among others, and should be understood to be modified in all cases by the term "about." Furthermore, when a range of values ​​is disclosed herein, such range is continuous and includes all values ​​from the minimum value to the maximum value, inclusive, unless otherwise specified. Furthermore, when such a range refers to integers, it includes all integers from the minimum value to the maximum value, inclusive, unless otherwise specified.

[0038] Additionally, when a range is described for a variable herein, the variable can be understood to include all values ​​within the described range, including the recited endpoints of the range. For example, the range "5 to 10" can be understood to include not only the values ​​5, 6, 7, 8, 9, and 10, but also any subranges such as 6 to 10, 7 to 10, 6 to 9, and 7 to 9, as well as any value between the integers within the described range, such as 5.5, 6.5, 7.5, 5.5 to 8.5, and 6.5 to 9. For example, the range "10% to 30%" can be understood to include values ​​such as 10%, 11%, 12%, 13%, and all integers up to and including 30%, as well as any subranges such as 10% to 15%, 12% to 18%, and 20% to 30%, as well as any value between the integers within the described range, such as 10.5%, 15.5%, 25.5%, etc.

[0039] One embodiment of the present invention is a self-assembly complex that utilizes a substance present in the body as a ligand, and includes a metal ion including at least one of cobalt (Co), silver (Ag), gadolinium (Gd), and iron (Fe); and at least one ligand that self-assembles with the metal ion; the self-assembly complex is reversibly performed and self-disassembled, and the self-assembly is carried out depending on at least one of the concentrations of the metal ion and the ligand, and the morphology of the self-assembly complex is controlled by the combination of the ligands.

[0040] Specifically, the self-assembly complex can form a self-assembly complex with metal ions at room temperature using substances present in the body as ligands, and can provide cost-competitive antibacterial and antiviral properties because it has low toxicity and does not require additional chemical treatment.

[0041] The metal ions may be cobalt ions, silver ions, gadolinium ions, or a gadolinium-iron ion mixture.

[0042] When the metal ion is cobalt, the self-assembly complex has paramagnetic properties and can be formed into a helical structure. When the metal ion is silver, the self-assembly complex can be formed into a spherical structure, and the size of the sphere can be determined. When the metal ion is gadolinium, the self-assembly complex has paramagnetic properties and the size can be controlled, and can be used as an MRI contrast agent. When the metal ion is a mixture of gadolinium and iron, the self-assembly complex has paramagnetic properties and the size can be controlled, and can be used as an MRI contrast agent.

[0043] Specifically, when the metal ion in the self-assembly complex is either gadolinium (Gd) ions or a mixture of gadolinium (Gd) ions and iron (Fe) ions, the self-assembly complex has magnetic properties and can be used as an MRI contrast agent. Specifically, the gadolinium (Gd) ions or the mixture of gadolinium (Gd) ions and iron (Fe) ions can self-assemble using substances present in the body as ligands to form a self-assembly complex. The self-assembly complex not only produces a magnetic material with low toxicity in the body and is capable of diagnosis, but also allows drugs to be easily loaded into the material, making it usable as a material for diagnosing and treating various diseases, including cancer.

[0044] The self-assembly complex may be self-disassembled by an external solution containing external ions. Specifically, the external solution may include a buffer solution. The self-assembly complex according to this embodiment spontaneously self-assembles and disassembles, and the self-disassembly may be accelerated by further including the buffer solution. The buffer solution may create an environment similar to the in vivo environment, and may accelerate the disassembly of the self-assembly complex by exchanging ions with the components of the self-assembly complex.

[0045] The self-assembly complex may be provided in a structure by aggregation of one or more of the metal ions and the ligand.

[0046] The ligand may include one or more of a phosphate and a phosphonate, and specifically, the ligand may include one or more of adenosine monophosphate, adenosine diphosphate, and adenosine triphosphate.

[0047] For example, the ligand may be AMP (adenosine monophosphate), ADP (adenosine diphosphate), ATP (adenosine triphosphate), TMP (thymidine monophosphate), TDP (thymidine diphosphate), TTP (thymidine triphosphate), CMP (cytidine monophosphate), CDP (cytidine diphosphate), CTP (cytidine triphosphate), GMP (guanosine monophosphate), GDP (guanosine diphosphate), GTP (guanosine triphosphate), UMP (uridine monophosphate), UDP (uridine diphosphate), diphosphate), UTP (uridine triphosphate), DNA, RNA, AEP (2-aminoethylphosphonic acid), TNA (threose nucleic acid), GNA (glycol nucleic acid), HNA (1,5-anhydrohexitol nucleic acid), ANA (1,5-anhydroatritol nucleic acid), FANA (2'-deoxy-2'-fluoroarabino nucleic acid), and CeNA (cyclohexenyl nucleic acid) may be at least one of these.

[0048] The ligand may include one or more phosphates, and the self-assembly complex may be provided in a structure by aggregation of the ligand with one or more of the metal ions.

[0049] When the metal ion is a cobalt ion, the structure is provided in a helical shape, and the size and number of helices of the structure can be controlled by the degree of mixing of the ligand with the number of the phosphates.

[0050] When the metal ion is one or more of cobalt, silver, gadolinium, and iron, the structure may have one or more of a helical, rod-like, and spherical shape, and the shape of the structure can be controlled by the number of phosphates and the degree of mixing of the ligands.

[0051] When the structure has a rod shape with an aspect ratio, the aspect ratio of the structure can be controlled by the degree of mixing of the ligand with respect to the number of the phosphates.

[0052] For example, the degree of aggregation or size of the structure formed by aggregation of the metal ions and the ligand can be controlled by the degree of mixing of the ligand relative to the number of phosphates contained in the ligand.

[0053] The self-assembly complex according to this embodiment further comprises an active ingredient therein, and the active ingredient may be one or more of adenosine, guanosine, uridine, cytidine, and doxorubicin.

[0054] The active ingredient may be supported by the self-assembly complex, or the active ingredient may be assembled together when the self-assembly complex is self-assembled and supported within the self-assembly complex.

[0055] The active ingredient can be released when the self-assembly complex is self-degraded. Therefore, the release time and rate of the active ingredient can be controlled by controlling the time for the self-assembly complex to self-degrade. The self-assembly complex may have different self-degradation rates depending on the ligand compounding ratio, and the self-assembly complex may be sequentially self-degraded from the surface at a predetermined rate. Therefore, the active ingredient can be released continuously at a constant rate during the time for the self-assembly complex to self-degrade. That is, the active ingredient may be released continuously at a constant rate during the release time.

[0056] When the metal ion is any one of cobalt (Co), gadolinium (Gd), and iron (Fe), the self-assembled complex may have paramagnetic properties.

[0057] When the metal ion is any one of cobalt (Co), gadolinium (Gd), and iron (Fe), the self-assembled complex can move a first distance when an externally applied magnetic field is applied.

[0058] When the metal ion is any one of cobalt (Co), gadolinium (Gd), and iron (Fe), the self-assembly complex has paramagnetic properties, and the magnetic moment can be adjusted depending on the formation conditions.

[0059] The metal ions and the ligands form a self-assembly complex through coordinate bonds, and adjacent ligands can be connected to each other through π-π interactions or hydrogen bonds.

[0060] For example, the metal ion can coordinate with the phosphate group of the ligand, AMP or ATP, to form a metal complex. The base moiety of the ligand contains an aromatic ring, which can form π-π interactions between the aromatic rings. Water molecules can bind to the metal ion, and the water molecules can form hydrogen bonds with the nitrogen of the base moiety.

[0061] The metal ion is gadolinium (Gd) ion or a mixture of gadolinium (Gd) and iron (Fe) ions, and the self-assembly complex is provided by aggregation of the metal ion and the ligand into a structure, and the size of the structure can be controlled by the concentration of the ligand and the reaction time.

[0062] In one embodiment of the present invention, when the metal ion is gadolinium (Gd) ion or a mixture of gadolinium (Gd) and iron (Fe) ions, the self-assembly complex may be loaded with a drug such as doxorubicin or adenosine, and the drug may be provided for sustained release by exhibiting a sustained release pattern for a desired period of time. The desired period may be a period selected from the range of 0.5 hours to 12 months, and the release rate of the drug may be controlled by the size of the self-assembly complex.

[0063] Examples of the present invention and comparative examples are described below. However, the following examples are merely preferred examples of the present invention, and the scope of the present invention is not limited to the following examples.

[0064] [Manufacturing example] 1. Preparation of self-assembled complexes containing cobalt ions Dissolve cobalt chloride, AMP (Adenosine monophosphate), and ATP (Adenosine triphosphate) in ultrapure water to a final concentration of 1M. Place the stock solution in a conical tube and add the calculated amount of ultrapure water. Add the adenosine phosphate solution and cobalt chloride solution in that order, vortex, and allow to react for 24 hours. After the 24-hour reaction is complete, remove any unreacted material and obtain self-assemblies by centrifugation at 10,000 RPM for 10 minutes. The self-assemblies are then settled and the supernatant is removed. Add ultrapure water to the same volume as the original and centrifuge again. This process is repeated twice.

[0065] 2. Preparation of self-assembled complexes containing silver ions Dissolve silver nitrate, AMP (Adenosine monophosphate), and ATP (Adenosine triphosphate) in ultrapure water to a final concentration of 1M. Place the stock solution in a conical tube and add the calculated amount of ultrapure water. Add the adenosine phosphate solution and silver nitrate solution, in that order, and vortex to mix well. Allow to react for 24 hours. After the 24-hour reaction is over, remove unreacted materials and obtain self-assemblies by centrifugation at 10,000 RPM for 10 minutes. The self-assemblies are then settled and the supernatant is removed. Add ultrapure water to the same volume as the original and centrifuge again. Repeat this process twice.

[0066] 3. Preparation of self-assembled complexes containing gadolinium ions Dissolve gadolinium chloride, AMP (Adenosine monophosphate), and ATP (Adenosine triphosphate) in ultrapure water to a final concentration of 1M. Place the stock solution in a conical tube and add the calculated amount of ultrapure water. Add the adenosine phosphate solution and gadolinium chloride solution, in that order, and vortex to mix well. Allow to react for 24 hours. After the 24-hour reaction is over, remove any unreacted material and obtain self-assemblies by centrifuging at 10,000 RPM for 10 minutes. The self-assemblies are then settled and the supernatant is removed. Add ultrapure water to the same volume as the original and centrifuge again. This process is repeated twice.

[0067] 4. Preparation of self-assembled complexes containing gadolinium-iron ions Dissolve gadolinium chloride, ferric chloride, adenosine monophosphate (AMP), and adenosine triphosphate (ATP) in ultrapure water to a final concentration of 1M. Place the stock solution in a conical tube and add the calculated amount of ultrapure water. Add adenosine phosphate solution, gadolinium chloride solution, and ferric chloride solution in this order, vortex, and let the reaction proceed for 24 hours or 10 minutes. After the reaction is complete, remove unreacted materials and obtain self-assemblies by centrifugation at 10,000 RPM for 10 minutes. The self-assemblies are then settled and the supernatant is removed. Add ultrapure water to the same volume as the original and centrifuge again. This process is repeated twice.

[0068] 5. Substances used in the experiment Cobalt(II) chloride (CAS: 7646-79-9, Sigma-Aldrich) Silver(I) nitrate (CAS: 7761-88-8, Taisho Reagents) Chromium(III) chloride hexahydrate (CAS:13450-84-5, Sigma-Aldrich) Iron(III) chloride hexahydrate (CAS:10025-77-1, Sigma-Aldrich) Adenosine-5'-monophosphate disodium salt (CAS: 4578-31-8, Alfa Aesar) Adenosine 5'-triphosphate disodium salt (CAS: 51963-61-2, Taisho Reagents) [Example]

[0069] A 10 ml mixed solution containing varying concentrations of AMP and ATP was prepared with cobalt chloride, and then reacted at room temperature for 24 hours to form a self-assembly complex.

[0070] [Table 1] [Example]

[0071] A 10 ml mixed solution containing varying concentrations of AMP and ATP was prepared with cobalt chloride, and then reacted at room temperature for 24 hours to form a self-assembly complex.

[0072] [Table 2] [Example]

[0073] A 10 ml mixed solution containing varying concentrations of AMP and ATP was prepared with silver nitrate, and then reacted at room temperature for 24 hours to form a self-assembly complex.

[0074] [Table 3] [Example]

[0075] A 10 ml mixed solution was prepared by varying the concentrations of gadolinium chloride, AMP, and ATP, and then reacted at room temperature for 24 hours to form a self-assembly complex.

[0076] [Table 4] [Example]

[0077] A mixed solution was prepared in 10 ml while maintaining the concentrations of gadolinium chloride, ferric chloride, AMP, and ATP, and then the reaction time at room temperature was adjusted to allow the formation of a self-assembly complex.

[0078] [Table 5] 1 is a schematic diagram illustrating a self-assembly complex using cobalt metal ions and adenosine monophosphate or mixed adenosine phosphate ligands in an embodiment of the present invention. Cobalt metal ions and adenosine monophosphate self-assemble to form a helical self-assembly complex, and the more adenosine triphosphate is added to the self-assembly complex, the less helical the self-assembly complex becomes. As the concentration of adenosine triphosphate increases, a rod-shaped self-assembly complex forms, and as the concentration of adenosine triphosphate increases, a spherical self-assembly complex forms.

[0079] Figure 2 shows that cobalt metal ions and adenosine monophosphate self-assemble to form a helical self-assembly complex, and the more adenosine triphosphate is contained in the self-assembly complex, the less helical it becomes. The morphology of the self-assembly complex can be confirmed using a scanning electron microscope.

[0080] Figure 3 shows that the aspect ratio is controlled when a self-assembly complex is formed between cobalt metal ions and a mixed ligand of adenosine monophosphate and adenosine triphosphate. As the concentration of adenosine triphosphate increases, the aspect ratio converges to 1, resulting in a spherical self-assembly complex. The morphology of the self-assembly complex can be confirmed using a scanning electron microscope.

[0081] Figure 4 shows the element ratio of the self-assembled complex of cobalt metal ions and adenosine monophosphate confirmed by transmission electron microscopy, and shows that the cobalt metal ions and adenosine monophosphate are present in the self-assembled complex at a ratio of 1:1.

[0082] 5 shows that when an external magnetic field is applied to a self-assembly complex using cobalt metal ions and adenosine monophosphate in an embodiment of the present invention, the self-assembly complex is dispersed in water and is attracted to the magnet within two hours of application. The paramagnetic properties of the cobalt self-assembly complex were confirmed by measurements using a vibrating sample magnetometer.

[0083] 6 is a schematic diagram showing a self-assembly complex using silver metal ions and adenosine monophosphate or mixed adenosine phosphate ligands among the phosphate ligands in an embodiment of the present invention, and the morphology of the self-assembly complex can be confirmed using a scanning electron microscope. It can be seen that the size of a single self-assembly complex increases as the amount of adenosine triphosphate included in the self-assembly complex increases.

[0084] FIG. 7 is a schematic diagram showing a magnetic self-assembly complex that can be used as a T1 contrast agent using gadolinium metal ions and adenosine monophosphate or mixed adenosine phosphate ligands among the phosphate ligands in an embodiment of the present invention; a magnetic self-assembly complex that can be used as a T1 and T2 contrast agent using adenosine monophosphate or mixed adenosine phosphate ligands among the phosphate ligands, which is a mixture of gadolinium metal ions and iron metal ions; and a self-assembly complex that can be loaded with various drugs when formed, allowing for magnetic local targeting and enabling simultaneous diagnosis and treatment.

[0085] FIG. 8 shows an example of the present invention in which the concentration of gadolinium metal ions and ligands are simultaneously adjusted to control the size of the self-assembled complex, which can be confirmed by scanning electron microscopy.

[0086] FIG. 9 shows an example of the present invention in which gadolinium and iron metal ions are mixed and reacted with a ligand to form a self-assembly complex. The size of the self-assembly complex can be controlled by quenching during the reaction, which can be confirmed by scanning electron microscopy.

[0087] Figure 10 shows the results of measurements using a vibrating sample magnetometer, which demonstrate that the gadolinium-based self-assembly complex and the gadolinium-iron-based self-assembly complex in the examples of the present invention are paramagnetic. It was also confirmed that the gadolinium-based self-assembly complex can be loaded with drugs, and that the loaded drugs are released from the buffer solution over several days.

[0088] Those skilled in the art will understand that the present invention may be embodied in other specific forms without changing the technical spirit or essential features thereof. Therefore, it should be understood that the above-described embodiments are illustrative in all respects and are not limiting. The scope of the present invention is defined by the claims set forth below rather than the above detailed description, and all modifications and variations derived from the meaning and scope of the claims and their equivalents should be construed as being within the scope of the present invention.

Claims

1. A self-assembly complex that utilizes a substance present in the body as a ligand, a metal ion that is cobalt (Co); and one or more ligands that self-assemble with the metal ion, the ligands being adenosine monophosphate and / or adenosine triphosphate; Including, Reversibly self-assembles or disassembles, the self-assembly complex has a structure formed by aggregation of the metal ions and one or more of the ligands, The self-assembled complex has a structure whose shape is one or more of a helix, a rod, and a sphere depending on the concentration of adenosine triphosphate in the combination of the metal ion and the ligand.

2. The self-assembled complex of claim 1 , wherein the self-assembled complex is self-disassembled by an external solution containing an external ion.

3. A self-assembly complex as described in claim 1, wherein the shape of the structure further varies depending on the degree of mixing of the ligand relative to the number of phosphates.

4. The self-assembly complex of claim 1 , wherein the aggregation or size of the structure varies depending on the degree of mixing of the ligand relative to the number of phosphates.

5. the self-assembled complex has a spherical structure, and the spherical structure further comprises an active ingredient therein; The self-assembly complex of claim 3 , wherein the active ingredient comprises one or more of adenosine, guanosine, uridine, cytidine, and doxorubicin.

6. The self-assembly complex of claim 1, wherein the self-assembly complex moves a first distance when an externally applied magnetic field is applied.

7. the metal ion and the ligand are linked by a coordinate bond, The self-assembly complex of claim 1, wherein adjacent ligands are linked by π-π interactions or hydrogen bonds.

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