Metal nano assembly constructed under non-micelle condition and application thereof

Abstract

The invention discloses a metal nano assembly constructed under a non-micelle condition, a metal precursor and a sulfydryl ligand are subjected to a reduction reaction in a dispersion system containing a block copolymer with the concentration lower than the critical micelle concentration, and the metal nano assembly is formed through in-situ assembly. According to the technical scheme, the preparation process is simplified, dependence on a high-concentration surfactant or a hard template in a traditional method is avoided, and effective regulation and control of the nano assembly structure and in-vivo metabolic behaviors are achieved by dynamically adjusting the proportion of the copper element in the gold-copper alloy. Experimental results show that the prepared nano assembly has good dispersibility and biocompatibility, can be biodegraded or cleared in vivo over time, solves the problem that traditional large-size gold nanoparticles are easily accumulated in non-specific organs for a long time, and has important application potential in the fields of biomedical imaging and diagnosis and treatment.

Description

Technical Field

[0001] This invention belongs to the field of nanomaterials and biomedical materials technology, specifically relating to a metal nanoassembly constructed under non-micelle conditions and its application. Background Technology

[0002] Metallic nanomaterials, due to their unique optical, electrical, and biocompatible properties, hold significant promise for applications in fields such as bioimaging, therapeutic integration, and drug delivery. In recent years, gold nanoparticles, as novel assemblies built from building blocks, have attracted widespread attention from scientists due to their unique optical properties. Assemblies of gold nanoparticles with different morphologies and functions have been successfully fabricated. Compared to individual gold nanoparticles, these assemblies exhibit stronger luminescence in the near-infrared band, making them more important for applications in biology and medicine. Furthermore, nanocomposite structures assembled from gold nanoparticles and block polymers can not only integrate the functions of individual structural units but also possess novel properties and functions, providing an effective and feasible approach for constructing multifunctional nanocomposite materials.

[0003] However, conventional preparation methods typically rely on high concentrations of surfactants or hard templates to construct stable nanostructures. The resulting large-sized, non-biodegradable AuNPs or AuNAs exhibit strong interactions with non-parenchymal liver cells, easily leading to non-specific organ accumulation and limiting their further applications. Furthermore, this not only increases costs, but surfactants also hinder the later applications of nanoassemblies. For example, large amounts of reducing agents and surfactants not only result in excessively high background signals in the nanoassemblies, hindering the detection of trace substances, but surfactants also impede the contact between the active sites of the nanoassemblies and the reactants or detectables, reducing reaction efficiency and detection sensitivity.

[0004] Therefore, it is of great significance to develop a novel preparation strategy that can construct stable nanoassemblies under mild conditions and has tunable in vivo behavior. Summary of the Invention

[0005] The purpose of this invention is to overcome at least one deficiency of the prior art and to provide a metal nano-assembly constructed under non-micelle conditions and its application.

[0006] The technical solution adopted in this invention is: In a first aspect, the present invention provides a metal nano-assembly constructed under non-micelle conditions, wherein a metal precursor and a thiol ligand undergo a reduction reaction in a dispersion system containing a block copolymer at a concentration below the critical micelle concentration, thereby forming a metal nano-assembly in situ. The molar ratio of the thiol ligand, the metal precursor, and the reducing agent is (1-10):1:(5-50). The metal precursor is obtained by mixing a copper precursor and a gold precursor; The proportion of copper in the total molar ratio of copper and gold is 0-80%.

[0007] In some embodiments, the proportion of copper in the total molar ratio of copper and gold is 40-70%.

[0008] In some embodiments, the block copolymer is selected from one or more of Pluronic F127, Pluronic F68, and Pluronic P123.

[0009] In some embodiments, the thiol ligand is selected from hydrophobic thiol ligands.

[0010] In some embodiments, the thiol ligand is selected from ethyl mercaptopropionate.

[0011] In some embodiments, the copper precursor is selected from at least one of copper nitrate, copper sulfate, or copper chloride.

[0012] In some embodiments, the gold precursor is selected from chloroauric acid or its salts.

[0013] In some embodiments, the reducing agent is selected from lithium borohydride, sodium borohydride, or potassium borohydride.

[0014] In some embodiments, the method for preparing the metal nanoassemblies is as follows: 1) Dissolve Pluronic F127 in deionized water, then add ethyl mercaptopropionate and mix thoroughly to form a homogeneous F127 / mercaptoligand mixed solution; 2) Then, a metal precursor is added to the homogeneous F127 / thiol ligand mixed solution. The proportion of copper in the total molar ratio of copper and gold in the metal precursor is 40-70%. After stirring evenly, sodium borohydride is added so that the molar ratio of thiol ligand: metal precursor: reducing agent in the system is 4:1:10, thereby causing a reduction reaction to obtain metal nanoassemblies.

[0015] Secondly, the application of the metal nanoassemblies provided in the first aspect of the present invention in the preparation of bioimaging materials.

[0016] The beneficial effects of this invention are: (1) To realize the construction of nano-assemblies under non-micelle conditions, avoiding traditional template dependence; (2) The nanostructure generation and assembly can be completed in one step, simplifying the process; (3) The structure and in vivo behavior can be controlled through the regulation of the interface microenvironment; (4) The method has good scalability and is applicable to a variety of block copolymers and thiol ligand systems. Attached Figure Description

[0017] Figure 1 This is a schematic diagram of the one-step preparation process of gold nanoassemblies and gold-copper alloy nanoassemblies according to the present invention.

[0018] Figure 2 These are transmission electron microscopy images of the fabricated nanoassemblies at 4 °C and 25 °C.

[0019] Figure 3 These are high-resolution transmission electron microscopy images of the metal core size distribution of nanoassemblies composed of different metals.

[0020] Figure 4 These are in vivo distribution behavior imaging results of different nanoassemblies and quantitative fluorescence results of liver. Detailed Implementation

[0021] The following disclosure provides many different implementations or examples for different ways of implementing the present invention.

[0022] The purpose of this invention is to provide a method for constructing metal nanoassemblies in a non-micelle state by utilizing the synergistic effect of block copolymers and thiol ligands, thereby achieving in-situ generation and controllable aggregation of metal nanostructures through interfacial microenvironment regulation, and expanding their application in the biomedical field.

[0023] The present invention adopts the following technical solution: First, block copolymers are added to the aqueous system to disperse them in the solution at a concentration below the critical micelle concentration, thereby avoiding the formation of stable micelle structures and providing an open interface microenvironment for the subsequent generation of metal nanostructures.

[0024] Subsequently, thiol-containing organic ligands were added to the system to enable them to synergistically interact with the block copolymer, thereby constructing a stable molecular dispersion system.

[0025] Based on this, a metal precursor solution is added to the system. The metal precursor can be a gold precursor or a mixed precursor of gold and copper.

[0026] Finally, a reducing agent is added to reduce the metal precursor. Under the synergistic regulation of the block copolymer and the thiol ligand, the metal nanostructure is generated in situ and simultaneously undergoes controllable aggregation, directly forming a metal nanoassembly.

[0027] By adjusting the type and composition ratio of the metal precursor, nanoassemblies with different metal compositions can be obtained, especially gold-copper alloy nanoassemblies with different copper contents. Example

[0028] 1) Preparation and structural characterization of metal nanoassemblies The specific preparation method of the metal nano-assemblies is as follows, and the preparation process is as follows: Figure 1 As shown: (1) First, the block copolymer Pluronic F127 was dissolved in deionized water at 25 °C to a final mass concentration of 0.33% (w / v), which is lower than the critical micelle concentration (CMC≈1%) of F127 at 25 °C. Then, the mercapto ligand EMP (ethyl mercaptopropionate) was added to the solution and mixed thoroughly to form a homogeneous F127 / mercaptoligand mixed solution.

[0029] (2) Then, prepare a mixed solution containing chloroauric acid and copper chloride. By adjusting the amount of copper chloride added, the proportion of copper element in the total metal molar amount of the mixed solution is 0%, 50%, and 80%, respectively.

[0030] (3) Finally, the mixed solution from step (2) was added to the homogeneous F127 / thiol ligand mixed solution. Following a mixing ratio of 4:1:10 for the thiol ligand, metal precursor, and reducing agent, the mixture was stirred until homogeneous. The reducing agent was then added to initiate a reduction reaction. Under the synergistic regulation of the block copolymer and the thiol ligand, the metal nanostructures were generated in situ and simultaneously underwent controlled aggregation, directly forming metal nanoassemblies. After the reaction, the product was purified by dialysis or ultrafiltration to obtain the target metal nanoassemblies. Based on the proportions of copper in the total metal molar amount of the mixed solution (0%, 50%, 80%), the obtained metal nanoassemblies were designated as AuNAs, AuCu50NAs, and AuCu80NAs, respectively.

[0031] The transmission electron microscopy morphology of the obtained metal nanoassemblies under different temperature conditions is as follows: Figure 2 As shown, it can be observed that the nanostructures aggregate in an orderly manner, forming a stable spherical morphology of the assembly structure, and there is no obvious fusion or collapse phenomenon between the particles.

[0032] The obtained metal core size distribution and high-resolution transmission electron microscopy results are as follows: Figure 3 As shown, the formation of the structure can be confirmed, and the metal cores inside the assembly are uniformly distributed with an average particle size of 2.3 ± 0.3 nm.

[0033] AuNAs, AuCu50NAs, and AuCu80NAs were administered intravenously to experimental animals, and near-infrared imaging was performed at predetermined time points. The in vivo distribution imaging results of the different nanoassemblies and the quantitative analysis results of liver fluorescence signals are as follows: Figure 4 As shown in the figure. By comparing the imaging results of different samples, it can be observed that there are differences in the in vivo distribution behavior of nanoassemblies with different metal compositions, indicating that the nanoassemblies prepared in this invention have controllable in vivo behavior.

[0034] The above is a further detailed description of the present invention and should not be considered as a limitation on the specific implementation of the present invention. For those skilled in the art, simple deductions or substitutions without departing from the concept of the present invention are all within the protection scope of the present invention.

Claims

1. A metal nanoassembly constructed under non-micelle conditions, characterized in that, Metal precursors and thiol ligands undergo a reduction reaction in a dispersion containing block copolymers with a concentration below the critical micelle concentration, and are assembled in situ to form metal nanoassemblies. The molar ratio of the thiol ligand, the metal precursor, and the reducing agent is (1-10):1:(5-50). The metal precursor is obtained by mixing a copper precursor and a gold precursor; The proportion of copper in the total molar ratio of copper and gold is 0-80%.

2. The metal nanoassembly according to claim 1, characterized in that, The proportion of copper in the total molar ratio of copper and gold is 40-70%.

3. The metal nanoassembly according to claim 1, characterized in that, The block copolymer is selected from one or more of Pluronic F127, Pluronic F68, and Pluronic P123.

4. The metal nanoassembly according to claim 1, characterized in that, The thiol ligand is selected from hydrophobic thiol ligands.

5. The metal nanoassembly according to claim 4, characterized in that, The thiol ligand is selected from ethyl mercaptopropionate.

6. The metal nanoassembly according to claim 1, characterized in that, The copper precursor is selected from at least one of copper nitrate, copper sulfate, or copper chloride.

7. The metal nanoassembly according to claim 1, characterized in that, The gold precursor is selected from chloroauric acid or its salts.

8. The metal nanoassembly according to claim 1, characterized in that, The reducing agent is selected from lithium borohydride, sodium borohydride, or potassium borohydride.

9. The metal nanoassembly according to any one of claims 1-8, characterized in that, The method for preparing the metal nano-assemblies is as follows: 1) Dissolve Pluronic F127 in deionized water, then add ethyl mercaptopropionate and mix thoroughly to form a homogeneous F127 / mercaptoligand mixed solution; 2) Then, a metal precursor is added to the homogeneous F127 / thiol ligand mixed solution. The proportion of copper in the total molar ratio of copper and gold in the metal precursor is 40-70%. After stirring evenly, sodium borohydride is added so that the molar ratio of thiol ligand: metal precursor: reducing agent in the system is 4:1:10, thereby causing a reduction reaction to obtain metal nanoassemblies.

10. The application of the metal nanoassemblies according to claim 1 in the preparation of bioimaging materials.

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