Construction of near-infrared fluorescent carbon dots based on metformin

Abstract

The invention discloses construction of a near-infrared fluorescent carbon dot based on metformin. The carbon dot is synthesized from metformin and an amino acid compound through a one-pot hydrothermal method. The preparation method comprises the following steps: mixing the metformin and the amino acid compound, dissolving in an alkaline solution, carrying out ultrasonic dissolution, transferring the solution into a polytetrafluoroethylene inner container, putting the inner container into a stainless steel high-pressure kettle, and carrying out heating reaction in a muffle furnace. After the reaction is finished and a reaction system is cooled to room temperature, taking out the solution and centrifuging to obtain supernate; and then putting the supernate into a dialysis bag for dialysis purification, and after dialysis is finished, freeze-drying the solution to obtain the carbon dots MACDs disclosed by the invention. The prepared carbon dot has excellent biocompatibility and optical property adjustability, retains the characteristic structure of metformin, has near-infrared fluorescence emission, and can realize disease diagnosis of organisms.

Description

Technical Field

[0001] The invention belongs to the field of material science and technology, and specifically relates to the construction of near-infrared fluorescent carbon dots based on metformin. Background Art

[0002] In recent years, with the development of molecular imaging and therapeutic diagnostics, the research on biological diagnostic agents has gradually attracted the attention of researchers. As a new type of carbon nanomaterial that has become more popular in recent years, carbon quantum dots have good biocompatibility and excellent photoluminescence performance, adjustable optical properties, and retain the active structure of raw materials. Therefore, the research on carbon dots as nanodiagnostic agents for diseases in bioimaging has become more and more extensive. However, most of the synthesized carbon dots currently only have visible (Vis) fluorescence, which has certain limitations in penetrating the epidermis of tissues. Synthesis of near-infrared fluorescence can meet the requirements of deep tissue imaging. At present, relevant studies have shown that doping heteroatoms (N, P, S, etc.) during the synthesis of carbon dots can effectively adjust the red shift of the fluorescence emission peak of carbon dots.

[0003] Metformin (Met) is a traditional drug used to treat type II diabetes. It contains a rich biguanide structure and is easy to construct a stable carbon core center. In addition, the N content of metformin is high, which can achieve near-infrared fluorescence regulation of carbon dots. Therefore, the use of metformin to synthesize carbon dots with near-infrared fluorescence has certain advantages. Amino acids, as essential substances for regulating human physiological functions and maintaining normal human metabolism, are crucial to human health and normal functions, and amino acids are rich in C, N, and O elements. Provide favorable conditions for the synthesis of near-infrared fluorescent carbon dots. Therefore, the use of metformin doped with amino acids is expected to further optimize the near-infrared fluorescence emission of carbon dots. Summary of the invention

[0004] In view of the shortcomings of the prior art and in order to solve the problems in the prior art, the purpose of the present invention is to provide a construction of near-infrared fluorescent carbon dots based on metformin, which have excellent biocompatibility, retain the specific structure of metformin, and have near-infrared fluorescence emission, thereby realizing disease diagnosis of organisms.

[0005] Unless otherwise specified, the percentages described in the present invention are all mass percentages.

[0006] To achieve the above purpose, the technical solution of the present invention is as follows:

[0007] Metformin and amino acid compounds are dissolved in an alkaline solution according to a certain feed ratio. After ultrasonic dissolution, the solution is transferred to a polytetrafluoroethylene liner, and then the liner is placed in a stainless steel autoclave and heated in a muffle furnace for reaction. After the reaction is completed, the reaction system is cooled to room temperature, and the solution is taken out and centrifuged to obtain a supernatant. The supernatant is then placed in a dialysis bag for dialysis purification. After the dialysis is completed, the above solution is freeze-dried to obtain the MACDs of the present invention.

[0008] Furthermore, the amino acid compound is one or more of tryptophan, threonine, aspartic acid, leucine and valine.

[0009] Furthermore, the alkaline solution is a sodium hydroxide solution with a solution concentration of 0.5-5 mol / L (molar volume ratio).

[0010] Furthermore, the optimal feed mass ratio of the reaction is metformin:amino acid=1:0.25-100.

[0011] Furthermore, the heating reaction temperature is 80-1000° C., and the reaction time is 0-48 hours.

[0012] Furthermore, the centrifugal speed is 800-10000 rpm, and the centrifugal time is 5-30 min; the dialysis bag has a molecular weight cutoff of 500-2000 Da, and the dialysis time is 24-48 hours.

[0013] A near-infrared fluorescent carbon dot based on metformin is constructed to realize the diagnosis of biological diseases.

[0014] Compared with the prior art, the present invention has the following advantages:

[0015] The synthesis method is simple and easy, the experimental operation is simple, and the raw materials are cheap and easy to obtain. The prepared carbon dots have high quantum yield and good stability. The carbon dots emit in the visible and near-infrared regions, and the fluorescence has strong tissue penetration, which has outstanding advantages compared with traditional blue-green carbon dots and can meet the needs of in vivo and in vitro biological imaging at the same time.

[0016] The synthesis method is controllable, and the emission wavelength can be adjusted by adjusting the reaction conditions (time, temperature). In particular, the emission intensity of the carbon dots can be adjusted by adjusting the feed mass ratio of the raw materials. The present invention uses metformin as a carbon source and doped amino acids to synthesize carbon dots with near-infrared fluorescence using a simple one-pot hydrothermal method. The synthesized carbon dots have good biocompatibility, retain the specific structure of metformin, have good in vivo imaging capabilities, and can realize disease diagnosis of organisms. In order to more clearly illustrate the embodiments of the present invention or the solutions in the prior art, the drawings required for use in the embodiments or the prior art descriptions are briefly introduced below. Obviously, the drawings described below are only some embodiments recorded in the present invention. For those skilled in the art, other drawings obtained based on these drawings still belong to the scope of the present invention without creative work. Figure 1 It is a schematic diagram of the preparation of the present invention; Figure 2 is the visible fluorescence emission spectrum of the carbon dots prepared in Example 1; Figure 3 is the near-infrared fluorescence emission spectrum of the carbon dots prepared in Example 1; Figure 4 is the XPS spectrum of the carbon dots prepared in Example 1. The full spectrum analysis of the carbon dots contains three peaks in total, namely C1s, O1s and N1s peaks at 284.8 eV, 400.1 eV and 531.4 eV respectively; Figure 5 This is the XPS peak spectrum of the carbon dots prepared in Example 1, corresponding to the peaks of C1s, O1s and N1s respectively. As shown in the figure, MACDs retains the characteristic groups of metformin and amino acids. Figure 6 is a transmission electron microscopy image of carbon dots prepared in Example 1; Figure 7 This is a fluorescence picture of the carbon dots prepared in Example 1 under a small animal in vivo imaging device. As shown in the figure, the carbon dots have obvious fluorescence compared with water under the in vivo imaging device.

Claims

1. Metformin and amino acid compounds are dissolved in an alkaline solution according to a certain feed ratio. After ultrasonic dissolution, the solution is transferred to a polytetrafluoroethylene liner, and then the liner is placed in a stainless steel autoclave and heated in a muffle furnace for reaction. After the reaction is completed, the reaction system is cooled to room temperature, and the solution is taken out and centrifuged to obtain a supernatant. The supernatant is then placed in a dialysis bag for dialysis purification. After the dialysis is completed, the above solution is freeze-dried to obtain the MACDs of the present invention.

2. The method for preparing MACDs according to claim 1, characterized in that The amino acid compound is one or more of tryptophan, threonine, aspartic acid, leucine and valine.

3. The method for preparing MACDs according to claim 1, characterized in that, The mass ratio of materials in the reaction is 1:0.25-100.

4. The method for preparing MACDs according to claim 1, wherein: The alkaline solution is a sodium hydroxide solution with a solution concentration of 0.5-5 mol / L (molar volume ratio), a reaction temperature of 80-1000° C., and a reaction time of 0-48 hours.

5. The method for preparing MACDs according to claim 1, wherein: The centrifugal speed is 800-10000 rpm, the centrifugal time is 5-30 min, the dialysis bag molecular weight cutoff is 500-3000 Da, and the dialysis time is 24-48 hours.

6. The use of MACDs in disease diagnosis and treatment according to any one of claims 1 to 6, characterized in that: In vivo imaging can be achieved in the near-infrared emission wave range of 600nm-1000nm.

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