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Targeting nanoparticle with GSH and esterase tumor microenvironment dual response as well as preparation method and application thereof

A technology for targeting nanoparticles and tumor microenvironment, applied in the field of targeting nanoparticles and their preparation, can solve the problems of low release efficiency, toxic side effects, poor stability, etc., and achieve the effect of efficient tumor cell proliferation and inhibition of tumor cell proliferation.

Active Publication Date: 2021-07-13
THE SEVENTH AFFILIATED HOSPITAL SUN YAT SEN UNIV SHENZHEN
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] The present invention provides a targeting nanoparticle with dual response to GSH and esterase tumor microenvironment and its preparation method and application to solve the problem of poor stability, low release efficiency and toxic side effects of existing stimulus-responsive nanocarriers. question

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  • Targeting nanoparticle with GSH and esterase tumor microenvironment dual response as well as preparation method and application thereof
  • Targeting nanoparticle with GSH and esterase tumor microenvironment dual response as well as preparation method and application thereof
  • Targeting nanoparticle with GSH and esterase tumor microenvironment dual response as well as preparation method and application thereof

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preparation example Construction

[0053] In a third aspect, the present invention also provides a method for preparing the targeted nanoparticles, comprising the following steps:

[0054] dissolving the drug-loaded substrate in an organic solvent to obtain a first material;

[0055] The first material and the stabilizer are placed in deionized water for mixing by using a nano-precipitation method, so as to obtain targeted nanoparticles.

[0056] In some embodiments, it also includes dissolving the drug (especially hydrophobic drug) in the organic solvent, so that the first material contains the drug-loaded substrate and the drug, thereby facilitating the embedding of the drug in the drug-loaded substrate Here, when the drug-loaded substrate and the stabilizer form a core-shell structure through nano-precipitation, the drug is embedded in the core, which can achieve a sustained release effect.

[0057] In some embodiments, the drug includes at least one of docetaxel (DTX), paclitaxel, camptothecin, methotrexat...

Embodiment 1

[0063] This embodiment provides a drug-loaded substrate and a method for preparing the drug-loaded substrate, wherein the drug-loaded substrate is poly[bis(thioglycolic acid)-1,4-butylene diester].

[0064] The preparation method of described poly[two (mercaptoacetic acid)-1,4-butylene diester] may further comprise the steps:

[0065] S11. In a well-ventilated environment, first add 3 mL (46.77 mmol) of bis(mercaptoacetic acid)-1,4-butylene diester solution into a clean and dry 38 mL thick-walled pressure-resistant bottle, then add DMSO, DMSO and di The molar ratio of (mercaptoacetic acid)-1,4-butylene diester is 5:1, stir for 1 min with a constant temperature magnetic stirrer at room temperature, and set the speed at 660 rpm;

[0066] S12. After the reaction solution of the above-mentioned bis(mercaptoacetic acid)-1,4-butylene diester and DMSO is fully contacted and mixed, use liquid nitrogen to rapidly cool the reaction solution to form a solid state, and then use the freezi...

Embodiment 2

[0075] This embodiment provides a drug-loaded substrate and a method for preparing the drug-loaded substrate, wherein the drug-loaded substrate is poly[bis(thioglycolic acid)-1,3-propylene diester].

[0076] The preparation method of described poly[two (mercaptoacetic acid)-1,3-propylene diester] comprises the following steps:

[0077] S21. In a well-ventilated environment, first add 8.0mL (49.2mmol) of bis(mercaptoacetic acid)-1,3-propanediester solution into a clean and dry 38mL thick-walled pressure-resistant bottle, and then add dimethyl methylene Sulfone (DMSO) solution, the molar ratio of DMSO to di(mercaptoacetic acid)-1,3-propylene diester is 5:1, stir at room temperature with a constant temperature magnetic stirrer for 1min, and set the speed at 660rpm;

[0078] S22. After the above-mentioned reaction solution of di(mercaptoacetic acid)-1,3-propanediester and DMSO is fully contacted and mixed, use liquid nitrogen to rapidly cool the reaction solution to form a solid s...

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Abstract

The invention relates to the technical field of medical materials, and particularly provides targeting nanoparticles with GSH and esterase tumor microenvironment dual response as well as a preparation method and an application thereof. The targeting nanoparticle contains a drug-loading base material and a stabilizer, the targeting nanoparticle has a core-shell structure, the drug-loading base material is a core, the stabilizer is a shell, and the drug-loading base material has a structural formula as shown in a formula (I). The targeting nanoparticle can be used as a nano targeting drug delivery system for treating cancers to controllably release cancer treatment drugs, so that the proliferation of tumor cells is efficiently inhibited to achieve the purpose of tumor treatment.

Description

technical field [0001] The invention belongs to the technical field of medical materials, and in particular relates to a targeting nanoparticle with dual responses of GSH and esterase tumor microenvironment, its preparation method and application. Background technique [0002] There are differences between tumor tissue and normal human tissue in terms of physical structure and chemical properties, which are mainly due to the biological specificity of tumor tissue, which will form a microenvironment in the human body that is different from normal tissue. For example, tumor cells have a higher The concentration of glutathione (GSH) in tumor cells is about 2mM to 20mM, which is 500 to 1000 times that of normal cells. In addition, in normal human tissues, the pH value is about 7.4; while the microenvironment of tumor cells is slightly acidic, and the pH value can be as low as about 6.5. And in different stages of tumor cells, the pH value of endosomes / lysosomes is also differen...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/52A61K47/24A61K47/32A61K47/22A61K47/34A61K31/198A61K31/337A61K31/4745A61K31/519A61K31/704A61P35/00
CPCA61K9/5146A61K9/5138A61K9/5192A61K31/337A61K31/4745A61K31/519A61K31/704A61K31/198A61P35/00Y02P20/55
Inventor 康洋何丹妮张铷和郑晓明徐作峰
Owner THE SEVENTH AFFILIATED HOSPITAL SUN YAT SEN UNIV SHENZHEN
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