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Preparation method of sericin-gadolinium pH responsive targeting tumor nuclear magnetic resonance contrast agent

A nuclear magnetic resonance and responsive technology, applied in the field of preparation of sericin-gadolinium pH-responsive targeted tumor nuclear magnetic resonance contrast agent, can solve the problems of inability to achieve accurate tumor imaging, non-specificity of Gd contrast agent, poor imaging effect, etc. , to enhance the effect of MRI imaging, improve biological safety, and achieve the effect of precise imaging

Active Publication Date: 2020-09-08
SOUTHWEST UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0008] To sum up, the problems existing in the prior art are: the existing Gd contrast agent is non-specific to the tissue, and cannot achieve accurate imaging of the tumor; Short action time, fast metabolism, low relaxation rate, and poor imaging effect; in order to improve imaging effect, the dosage has to be increased, which may bring potential toxicity

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  • Preparation method of sericin-gadolinium pH responsive targeting tumor nuclear magnetic resonance contrast agent
  • Preparation method of sericin-gadolinium pH responsive targeting tumor nuclear magnetic resonance contrast agent
  • Preparation method of sericin-gadolinium pH responsive targeting tumor nuclear magnetic resonance contrast agent

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preparation example Construction

[0063] The preparation method of the pH-switchable responsive nuclear magnetic resonance imaging contrast agent provided by the present invention comprises:

[0064] The amino group of sericin protein and the aldehyde group of gadolinium acetate hexahydrate are reacted in one step to form a Schiffer base by a two-step method, and then gadolinium ions are supplemented by electrostatic adsorption of gadolinium chloride hexahydrate.

[0065] Such as figure 1 As shown, the preparation method of the sericin-gadolinium pH-responsive targeting tumor MRI contrast agent provided by the embodiment of the present invention specifically includes the following steps:

[0066] S101: Sericin protein was extracted by 0.02M sodium bicarbonate alkali boiling method, and then vacuum freeze-dried.

[0067] S102: Use 0.07M KOH and 20% ethanol to dissolve the sericin, put it in a water bath at 60° C., and filter it to obtain a clear and transparent solution after it is completely dissolved.

[0068...

Embodiment 1

[0073] 1. Results and discussion

[0074] 1.1 Synthesis and characterization

[0075] The invention adopts the method of titrating to saturation to carry out direct Schiffer base reaction between the amino group of sericin and the aldehyde group of gadolinium acetate hexahydrate, and then supplements gadolinium ions by electrostatic adsorption of gadolinium chloride hexahydrate. Whole reaction adopts two-step method to carry out: ( image 3 a) 0.02M sodium bicarbonate alkali boiling method to extract sericin and freeze-dry; use 0.07M KOH and 20% ethanol to dissolve sericin, put it in a water bath at 60°C, and take a clear and transparent solution by suction filtration after it is completely dissolved; Under the protection of Mβ-mercaptoethanol, add 0.03M gadolinium acetate hexahydrate dropwise to react with the above solution; after the reaction is saturated, add 2M gadolinium chloride hexahydrate solution and titrate to supersaturation; dialyze for 72 hours to remove free su...

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Abstract

The invention belongs to the technical field of magnetic resonance imaging (MRI) contrast agents, and discloses a preparation method of a sericin-gadolinium pH responsive targeting tumor nuclear magnetic resonance contrast agent. The contrast agent is used for enhancing MRI research of tumor tissues, sericin, gadolinium acetate hexahydrate and gadolinium chloride hexahydrate are adopted as raw materials, and the nano contrast agent SS@GAH-GdCl3 is synthesized through a Schiff base reaction. Amino groups of the sericin and aldehyde groups of the gadolinium acetate hexahydrate are subjected to aone-step reaction by a two-step method to form Schiff base, and gadolinium ions are supplemented through electrostatic adsorption of the gadolinium chloride hexahydrate. The contrast agent prepared by the method can smoothly pass through normal tissues and blood vessels, and the surface potential of the contrast agent can be automatically reversed at a tumor part to enter tumor tissues, so that the uptake of tumor cells is increased, and the precise MRI contrast of solid tumors is realized; and the metabolism time of the nano contrast agent is remarkably prolonged by 30-60 min, and is far longer than the pharmacokinetic time of a commercial gadodiamide injection.

Description

technical field [0001] The invention belongs to the technical field of nuclear magnetic resonance imaging contrast agents, and in particular relates to a preparation method of a sericin-gadolinium pH-responsive targeting tumor nuclear magnetic resonance contrast agent. Background technique [0002] MRI is currently one of the most effective diagnostic imaging methods in clinical practice. It has the advantages of non-invasiveness, no radiation damage, high resolution of soft tissue, multi-nuclear multi-parameter imaging, and arbitrary slice scanning. It is the preferred method for central nervous system and neurovascular imaging, especially These are small neoplastic lesions that are not recognized by other detection methods. MRI has become an important tool for molecular and cellular imaging because of its ability to provide high-resolution images of soft tissue anatomy. For example, it may facilitate early detection of lesions and precisely deliver targeted drugs to tumor...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K49/14
CPCA61K49/14
Inventor 王叶菁黄子轩何华伟赵萍夏庆友
Owner SOUTHWEST UNIV
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