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pH-responsive T1-T2 double-activated nanoprobe as well as preparation method and application thereof

A technology of T1-T2 and nano-probes, which is applied in the field of nano-materials and molecular imaging, can solve the problems of insufficient sensitivity and specificity of dual-modal contrast agents, complex preparation processes, etc., and achieve improved biocompatibility and simple process , Activation Effect Enhanced Effect

Active Publication Date: 2022-02-15
SHANGHAI FIRST PEOPLES HOSPITAL
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0006] In order to solve the problem of insufficient sensitivity and specificity of dual-modal contrast agents in the prior art and complicated preparation process, the present invention discloses a pH-responsive T1 -T2 dual-activation nanoprobe and its preparation method and application, the nanoprobe has pH responsiveness, activates T1 and T2 signals simultaneously under the acidic condition of the tumor microenvironment, and finally improves the performance and accuracy of imaging; at the same time , the nanoprobe has good biocompatibility and biodegradability, and the preparation method is simple, which is conducive to clinical transformation and application

Method used

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  • pH-responsive T1-T2 double-activated nanoprobe as well as preparation method and application thereof
  • pH-responsive T1-T2 double-activated nanoprobe as well as preparation method and application thereof
  • pH-responsive T1-T2 double-activated nanoprobe as well as preparation method and application thereof

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preparation example Construction

[0054] The preparation method of the pH-responsive T1-T2 double-activated nanoprobe of the present invention comprises the following steps:

[0055] S1, using gadolinium nitrate and transferrin as raw materials, adding NaOH solution, and reacting at 37°C, the reaction solution was refrigerated and centrifuged to take the supernatant, after ultrafiltration and redissolution, transferrin chelated gadolinium was obtained, and stored at 4°C for later use;

[0056] S2, using transferrin chelated gadolinium and aminated SPIO as raw materials, adding a dialdehyde-based polyethylene glycol solution, and reacting at room temperature to obtain the pH-responsive T1-T2 dual-activated nanoprobe;

[0057] Wherein, in step S1, the concentration of the NaOH solution is 1mol / L, and the dosage ratio of the gadolinium nitrate, transferrin and NaOH solution is 5-6mg: 15-25mg: 0.1-0.2mL;

[0058] The specific steps of ultrafiltration are: put the supernatant into an ultrafiltration tube with a mol...

Embodiment 1

[0067] Embodiment 1, the preparation of TGPS nanoprobe

[0068] (1) Preparation of transferrin-chelated gadolinium (Tf@Gd)

[0069] Weigh gadolinium nitrate Gd(NO 3 ) 3 5.4mg and 20mg of transferrin Tf were dissolved in 1.2mL of pure water (the ambient temperature was maintained at 37°C), stirred for 5 minutes, and after the dissolution was complete, 0.12mL of 1M NaOH solution was added, and the reaction was continued at 37°C for 12h (constant speed Stir slowly, not violently). After the reaction, the reactant was centrifuged at 10,000rpm for 30min with a refrigerated centrifuge, and the supernatant was extracted, put into an ultrafiltration tube (30KDa), and ultrafiltered at 5,000rpm for 30min to remove excess Gd 3+ ions, and then redissolve the product in the upper layer of the ultrafiltration tube in 1mL pure water to obtain transferrin-chelated gadolinium (Tf@Gd). mL of probe solution and stored in a refrigerator at 4°C.

[0070] Take out part of Tf@Gd and test it wi...

Embodiment 2

[0078] Embodiment 2, the preparation of TGPS nanoprobe

[0079] (1) Preparation of transferrin-chelated gadolinium (Tf@Gd)

[0080] Weigh gadolinium nitrate Gd(NO 3 ) 3 5mg and 15mg of transferrin Tf were dissolved in 1.2mL pure water (the ambient temperature was maintained at 37°C), stirred for 5 minutes, and after the dissolution was complete, 0.1 2mL of 1M NaOH solution was added, and the reaction was continued at 37°C for 12h (constant speed Stir slowly, not violently). After the reaction, the reactant was centrifuged at 10,000rpm for 30min with a refrigerated centrifuge, and the supernatant was extracted, put into an ultrafiltration tube (30KDa), and ultrafiltered at 5,000rpm for 30min to remove excess Gd 3+ ions, and then redissolve the product in the upper layer of the ultrafiltration tube in 1mL pure water to obtain transferrin-chelated gadolinium (Tf@Gd). mL of probe solution and stored in a refrigerator at 4°C.

[0081] (2) preparation of bisaldehyde group poly...

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Abstract

The invention discloses a pH responsive T1-T2 double-activated nanoprobe as well as a preparation method and application thereof. According to the method, Tf (at) Gd and aminated SPIO are simultaneously encapsulated in micelles, so the nanoprobe with distance controllability and acidic microenvironment responsiveness is prepared. The probe can simultaneously realize double activation of T1 and T2 signals under the tumor microenvironment acidic condition, and the activation effect is enhanced along with the increase of acidity and time, so that the imaging performance and accuracy can be remarkably improved, and the diagnosis of early-stage tiny metastatic tumors and the detection efficiency of inflammatory lesions are realized; meanwhile, the nanoprobe has good biocompatibility and biodegradability, the preparation method is simple, and clinical conversion application is facilitated.

Description

technical field [0001] The invention belongs to the technical field of nanomaterials and molecular imaging, and in particular relates to a pH-responsive T1-T2 double-activated nanoprobe and its preparation method and application. Background technique [0002] Magnetic Resonance Imaging (MRI) has the advantages of high resolution, no ionizing radiation damage, multi-parameter, and multi-sequence imaging, and has become one of the most powerful detection methods in contemporary clinical diagnosis. [0003] In order to highlight the differences between tissues, especially the difference between normal tissues and diseased parts, contrast agents are often used to improve the imaging contrast. According to the principle of action, MRI contrast agents can be divided into longitudinal relaxation contrast agents (T1 contrast agents) and transverse relaxation contrast agents (T2 contrast agents). T1 contrast agents mainly accelerate T1 relaxation and produce "brightness" in T1-weight...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K49/14B82Y40/00
CPCA61K49/14B82Y40/00
Inventor 王中领曹蓉朱仪陈安
Owner SHANGHAI FIRST PEOPLES HOSPITAL
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