A hydrophilic Co 3 O 4 Preparation method and application of nanospheres

Abstract

The invention discloses a hydrophilic Co 3 O 4 Preparation method and application of nanospheres, the preparation method comprising: dispersing cobalt salt in a mixture of isopropanol and glycerol, stirring, transferring the mixture to a reaction kettle, performing solvent thermal reaction at 160-240°C for 6-24h, centrifuging, washing, drying, obtaining a cobalt-based precursor, and then performing high temperature heat treatment at 150-600°C for 0.5-24h to obtain black Co 3 O 4 The nanospheres are mixed with amino polyethylene glycol and stirred to obtain the hydrophilic Co 3 O 4 The nanospheres are 200 to 600 nm in size and have a T 2 ‑weighted MRI performance with T under glutathione and / or acidic conditions 1 ‑Weighted sum T 2 ‑weighted enhanced magnetic resonance imaging performance, can be used as or to prepare T 1 ‑Weighted sum T 2 -Weighted dual-mode weighted MR contrast agents are used in the field of cancer diagnosis and have broad application prospects.

Description

Technical Field

[0001] The invention belongs to the field of multifunctional materials, and particularly relates to a preparation method and application of hydrophilic Co3O4 nanospheres. Background Art

[0002] Magnetic resonance imaging (MRI) is an imaging technology that uses an external high-frequency magnetic field to generate signals from substances in the body radiating energy to the surrounding environment. It is currently the main technology for cancer diagnosis because it can reliably distinguish tumors from surrounding normal tissues without exposing patients to radiation such as X-rays.

[0003] With the rapid development of interdisciplinary studies in medicine and engineering, various nanomaterial-based contrast agents have been developed for cancer diagnosis, such as iron (Fe), manganese (Mn), and gadolinium (Gd)-based materials. This type of material can not only be used as an MR contrast agent to improve the MR imaging effect; at the same time, due to the multi-variable valence states of transition metals, it has the effect of further enhancing MR under microenvironment conditions such as high expression of glutathione (GSH) and weak acid in tumor tissue. However, iron (Fe)-based contrast agents are mainly T2-MR weighted imaging effects, and manganese (Mn) and gadolinium (Gd) are mostly used as T1-MR weighted contrast agents. This single MR imaging mode is often susceptible to false positives caused by tissue blood. Therefore, the development of an MR contrast agent with enhanced tumor microenvironment response and T1- / T2-dual-mode weighting is of great significance for improving the accuracy of tumor diagnosis. Summary of the invention

[0004] In order to solve the above technical problems, the main purpose of the present invention is to provide a method for preparing hydrophilic Co3O4 nanospheres, the raw materials required by the method are easily available and low in price, and the synthesis method is mild.

[0005] Another object of the present invention is to provide the use of the above-mentioned hydrophilic Co3O4 nanospheres in the preparation of MR contrast agents with T1-weighted and T2-weighted dual-mode weighted enhancement.

[0006] To achieve the above object, the present invention adopts the following technical solutions:

[0007] The present invention provides a method for preparing hydrophilic Co3O4 nanospheres, comprising the following steps:

[0008] Step 1: a certain amount of cobalt salt is dispersed in a mixture of isopropanol and glycerol, stirred, and transferred to a reaction kettle after being mixed evenly, and subjected to solvent thermal reaction at 160-240° C. for 6-24 hours, centrifuged, washed, and dried to obtain a cobalt-based precursor;

[0009] Step 2: The cobalt-based precursor obtained in step 1 is subjected to a high temperature heat treatment at 150 to 600° C. for 0.5 to 24 hours to obtain black Co3O4 nanospheres;

[0010] Step 3: The black Co3O4 nanospheres obtained in step 2 are mixed with amino polyethylene glycol to obtain hydrophilic Co3O4 nanospheres.

[0011] Preferably, in step 1, the cobalt salt is selected from one or a combination of two or more of cobalt nitrate, cobalt acetate or cobalt chloride.

[0012] Preferably, in step 1, the molar ratio of isopropanol to glycerol is 2 to 6:1.

[0013] Preferably, in step 3, the mass ratio of the black Co3O4 nanospheres to aminopolyethylene glycol is 1:1-10.

[0014] Preferably, in step 3, the hydrophilic Co3O4 nanospheres have T2-weighted magnetic resonance imaging performance in a magnetic field.

[0015] Preferably, in step 3, the hydrophilic Co3O4 nanospheres have T1-weighted conversion and T2-weighted enhanced magnetic resonance imaging performance under stimulation of glutathione and / or acidic conditions.

[0016] Preferably, in step 3, the size of the hydrophilic Co3O4 nanospheres is 200 to 600 nm.

[0017] The present invention also provides the use of the hydrophilic Co3O4 nanospheres in preparing a MR contrast agent with dual-mode weighting of T1-weighting and T2-weighting.

[0018] Preferably, the MR contrast agent has T2-weighted magnetic resonance imaging performance; or has T1-weighted conversion and T2-weighted enhanced magnetic resonance imaging performance under glutathione and / or acidic condition stimulation.

[0019] Compared with the prior art, the present invention has the following beneficial effects:

[0020] The hydrophilic Co3O4 nanospheres prepared by the present invention have T2-weighted magnetic resonance imaging performance in a magnetic field, and have T1-weighted and T2-weighted enhanced magnetic resonance imaging performance under the stimulation of glutathione and acidic conditions. They can be used as or prepared as MR contrast agents with T1-weighted and T2-weighted dual-mode weightings for the field of cancer diagnosis. The preparation method thereof has the advantages of being environmentally friendly, the required raw materials being easily available, the price being low, the operation process being simple, and the like. BRIEF DESCRIPTION OF THE DRAWINGS

[0021] Figure 1 This is a scanning electron microscope image of the hydrophilic Co3O4 nanospheres prepared in Example 1.

[0022] Figure 2This is a transmission electron microscopy image of the hydrophilic Co3O4 nanospheres prepared in Example 1.

[0023] Figure 3 This is an elemental surface scanning image of the hydrophilic Co3O4 nanospheres prepared in Example 1.

[0024] Figure 4 This is the XRD image of the hydrophilic Co3O4 nanospheres prepared in Example 1.

[0025] Figure 5 These are magnetic resonance imaging images of hydrophilic Co3O4 nanospheres of different concentrations prepared in the examples.

[0026] Figure 6 These are magnetic resonance imaging images of hydrophilic Co3O4 nanospheres of different concentrations prepared in the examples under GSH stimulation.

[0027] Figure 7 The NMR relaxation rate changes of hydrophilic Co3O4 nanospheres with different concentrations prepared in the examples under weakly acidic conditions and GSH stimulation. DETAILED DESCRIPTION

[0028] The present invention will be further described below in conjunction with specific examples. It should be understood that these examples are only used to illustrate the present invention and are not intended to limit the scope of the present invention.

[0029] Example 1

[0030] In this embodiment, hydrophilic Co3O4 nanospheres are prepared in the following steps:

[0031] (1) Dispersing 100 mg of cobalt nitrate in a mixture of 30 mL of isopropanol and 6 mL of glycerol, stirring, transferring the mixture to a reaction vessel, performing a solvent thermal reaction at 180° C. for 8 h, centrifuging, washing, and drying to obtain a cobalt-based precursor;

[0032] (2) heat treating a certain amount of the obtained cobalt-based precursor at 200°C for 8.0 h to obtain black Co3O4 nanospheres;

[0033] (3) The obtained black Co3O4 nanospheres were mixed with amino polyethylene glycol (mass ratio 1:5) to obtain hydrophilic Co3O4 nanospheres, the performance of which is characterized as follows: Figures 1 to 4 As shown, it can be seen that the size of the hydrophilic Co3O4 nanospheres is in the range of 200 to 600 nm, and the particle size is uniform.

[0034] Example 2

[0035] In this embodiment, hydrophilic Co3O4 nanospheres are prepared in the following steps:

[0036] (1) Dispersing 500 mg of cobalt nitrate in a mixture of 30 mL of isopropanol and 6 mL of glycerol, stirring, transferring the mixture to a reaction vessel, performing a solvent thermal reaction at 180° C. for 8 h, centrifuging, washing, and drying to obtain a cobalt-based precursor;

[0037] (2) heat treating a certain amount of the obtained cobalt-based precursor at 200°C for 8.0 h to obtain black Co3O4 nanospheres;

[0038] (3) A certain amount of the obtained black Co3O4 nanospheres was mixed with amino polyethylene glycol (mass ratio 1:5) to obtain hydrophilic Co3O4 nanospheres.

[0039] Example 3

[0040] In this embodiment, hydrophilic Co3O4 nanospheres are prepared in the following steps:

[0041] (1) Dispersing 100 mg of cobalt nitrate in a mixture of 30 mL of isopropanol and 6 mL of glycerol, stirring, transferring the mixture to a reaction vessel, performing a solvent thermal reaction at 180° C. for 24 h, centrifuging, washing, and drying to obtain a cobalt-based precursor;

[0042] (2) heat treating a certain amount of the obtained cobalt-based precursor at 200°C for 8.0 h to obtain black Co3O4 nanospheres;

[0043] (3) A certain amount of the obtained black Co3O4 nanospheres was mixed with amino polyethylene glycol (mass ratio 1:5) to obtain hydrophilic Co3O4 nanospheres.

[0044] Example 4

[0045] In this embodiment, hydrophilic Co3O4 nanospheres are prepared in the following steps:

[0046] (1) Dispersing 100 mg of cobalt nitrate in a mixture of 30 mL of isopropanol and 6 mL of glycerol, stirring, transferring the mixture to a reaction vessel, performing a solvent thermal reaction at 180° C. for 24 h, centrifuging, washing, and drying to obtain a cobalt-based precursor;

[0047] (2) a certain amount of the obtained cobalt-based precursor was heat treated at 450°C for 2.0 h to obtain black Co3O4 nanospheres;

[0048] (3) A certain amount of the obtained black Co3O4 nanospheres were mixed with amino polyethylene glycol (mass ratio 1:5) to obtain hydrophilic Co3O4 nanospheres.

[0049] Example 5

[0050] The nuclear magnetic resonance imaging performance of the hydrophilic Co3O4 nanospheres obtained in Example 1 was measured.

[0051] The hydrophilic Co3O4 nanosphere dispersions of different concentrations were prepared using PBS (pH 7.36) buffer and scanned using a 0.5TMesoMR23-060H-I magnetic resonance imaging system. Figure 5 It can be seen that as the concentration of the hydrophilic Co3O4 nanosphere dispersion increases, the T2-weighted imaging image becomes darker (the contrast becomes larger), and the contrast of the T1-weighted imaging image does not differ much, indicating that the hydrophilic Co3O4 nanospheres prepared in Example 1 have a T2-weighted nuclear magnetic resonance imaging effect.

[0052] Example 6

[0053] The nuclear magnetic resonance imaging performance of the hydrophilic Co3O4 nanospheres obtained in Example 1 was measured.

[0054] The hydrophilic Co3O4 nanosphere dispersions of different concentrations were prepared using PBS (pH 7.36) buffer and treated with GSH, and then scanned using a 0.5T MesoMR23-060H-I magnetic resonance imaging system. Figure 6 It can be seen that with the increase of the concentration of the hydrophilic Co3O4 nanosphere dispersion, the T2-weighted imaging picture becomes darker and darker, and the MR contrast is greater than that without GSH treatment at the same concentration; at the same time, the T1-weighted imaging also shows a concentration-dependent effect, and the picture becomes brighter and brighter, indicating that the hydrophilic Co3O4 nanospheres prepared in Example 1 have glutathione-responsive T1-weighted conversion and T2-weighted enhanced magnetic resonance imaging performance.

[0055] Example 7

[0056] The nuclear magnetic resonance imaging performance of the hydrophilic Co3O4 nanospheres obtained in Example 1 was measured.

[0057] The hydrophilic Co3O4 nanosphere dispersions of different concentrations were prepared using PBS (pH 5.27) buffer and treated with GSH. They were then scanned using a 0.5T MesoMR23-060H-I magnetic resonance imaging system. Figure 7 It can be seen that with the increase in the concentration of the hydrophilic Co3O4 nanosphere dispersion, both T2-weighted and T1-weighted showed a concentration-dependent increase in MR relaxation rate, indicating that the hydrophilic Co3O4 nanospheres prepared in Example 1 have T1-weighted conversion and T2-weighted enhanced magnetic resonance imaging performance responsive to glutathione and acidic conditions.

[0058] The above description of the embodiments is to facilitate the understanding and use of the present invention by those skilled in the art. It is obvious that those skilled in the art can easily make various modifications to these embodiments and apply the general principles described herein to other embodiments without having to go through creative work. Therefore, the present invention is not limited to the above embodiments, and improvements and modifications made by those skilled in the art based on the principles of the present invention without departing from the scope of the present invention should be within the scope of protection of the present invention.

Claims

1. A method for preparing hydrophilic Co3O4 nanospheres, characterized in that: The following steps are involved: Step 1, a certain amount of cobalt salt is dispersed in a mixture of isopropanol and glycerol, stirred, and transferred to a reaction kettle after being evenly mixed, and subjected to solvent thermal reaction at 160-240° C. for 6-24 hours, centrifuged, washed, and dried to obtain a cobalt-based precursor; Step 2: The cobalt-based precursor obtained in step 1 is subjected to a high temperature heat treatment at 150 to 600° C. for 0.5 to 24 hours to obtain black Co3O4 nanospheres; Step 3: The black Co3O4 nanospheres obtained in step 2 are mixed and stirred with amino polyethylene glycol to obtain hydrophilic Co3O4 nanospheres with a size of 200 to 600 nm; In step 1, the molar ratio of isopropanol to glycerol is 2 to 6:1; In step 3, the mass ratio of the black Co3O4 nanospheres to the amino polyethylene glycol is 1:1-10; the hydrophilic Co3O4 nanospheres have T2-weighted magnetic resonance imaging performance in a magnetic field; Or the hydrophilic Co3O4 nanospheres have T1-weighted conversion and T2-weighted enhanced magnetic resonance imaging performance under the stimulation of glutathione and / or acidic conditions.

2. The method for preparing hydrophilic Co3O4 nanospheres according to claim 1, characterized in that: In step 1, the cobalt salt is selected from one or a combination of two or more of cobalt nitrate, cobalt acetate or cobalt chloride.

3. Use of a hydrophilic Co3O4 nanosphere in the preparation of a MR contrast agent with dual-mode weighting of T1-weighting and T2-weighting, wherein the hydrophilic Co3O4 nanosphere is prepared by the preparation method of the hydrophilic Co3O4 nanosphere according to claim 1 or 2; The MR contrast agent has T2-weighted magnetic resonance imaging performance; or has T1-weighted conversion and T2-weighted enhanced magnetic resonance imaging performance under glutathione and / or acidic condition stimulation.

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