A tumor microenvironment-responsive self-assembly integrated diagnosis and treatment reagent and its preparation method

A tumor microenvironment and responsive technology, which can be applied in preparations for in vivo experiments, antineoplastic drugs, photodynamic therapy, etc., can solve the problems of low delivery efficiency of photosensitizers, poor tumor retention ability, poor diagnostic sensitivity, etc., to achieve Good stability and biocompatibility, improved diagnostic accuracy, reproducible effect

Active Publication Date: 2021-06-04
JILIN JUNTONGXING BIOTECH
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0006] The purpose of the present invention is to provide a tumor microenvironment-responsive self-assembled diagnosis and treatment integrated reagent and its preparation method in order to overcome the above-mentioned defects in the prior art. , poor tumor retention ability, poor diagnostic sensitivity and low treatment efficiency, and realize the function of simultaneous diagnosis and treatment

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  • A tumor microenvironment-responsive self-assembly integrated diagnosis and treatment reagent and its preparation method
  • A tumor microenvironment-responsive self-assembly integrated diagnosis and treatment reagent and its preparation method
  • A tumor microenvironment-responsive self-assembly integrated diagnosis and treatment reagent and its preparation method

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Embodiment 1

[0041] (1) 400mg poly(isobutylene-alt-maleic anhydride) (average molecular weight 6000), 500mg polyethylene glycol monomethyl ether (average molecular weight 2000) with amine groups at one end and 500mg 1-(3-aminopropyl ) imidazoles were placed in a 100mL three-neck flask with a magnetic rotor, and poured into 30mL of anhydrous dimethyl sulfoxide to dissolve it completely, and the mixed solution was reacted for 12 in an oil bath at 60 degrees Celsius under nitrogen protection. Hour. Subsequently, the above solution was added dropwise into 10 mL of anhydrous dimethyl sulfoxide containing 600 mg cystamine, and the reaction was continued for 12 hours under nitrogen protection. The reacted solution was loaded into a dialysis membrane with a molecular weight cut-off of 7000, purified by dialysis with excess deionized water for 60 h, and then dried by freezing (-48°C) to obtain a multifunctional polymer ligand intermediate (PIMA-PEG-API- Cystamine), stored in freezer (-20°C).

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Embodiment 2

[0049] (1) 1g of sodium hyaluronate (sodium hyaluronate) (average molecular weight 2.344*10 5 ), 570mg 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC·HCl) and 294mg N-hydroxysuccinimide (NHS) were placed together in 250mL with magnetic Rotor three-necked flask, and pour 100 mL of aqueous solution to make it completely dissolved, and the mixed solution was reacted in an oil bath at room temperature under nitrogen protection for 12 hours. Subsequently, 620 mg of polyethylene glycol monomethyl ether (average molecular weight 2000) with a single end being an amine group and 60 mg of 1-(3-aminopropyl) imidazole were added to the above solution, and the reaction was continued for 12 hours under nitrogen protection. The reacted solution was added dropwise into 10 mL of an aqueous solution containing 200 mg of cystamine, and the reaction was continued for 12 hours under nitrogen protection. Finally, the solution was placed in a dialysis membrane with a molecular wei...

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Abstract

A tumor microenvironment-responsive self-assembly diagnosis and treatment integration reagent and a preparation method thereof belong to the field of self-assembly nano-biomedical technology. The integrated diagnosis and treatment reagent obtained in the present invention is composed of free carboxyl groups generated in multifunctional polymer ligands and trivalent metal gadolinium ions. It has the ability to induce surface charge conversion in the acidic environment outside tumor cells and promote cell uptake. It also has the function of glutathione in tumor cells to activate fluorescent signals and photodynamic therapy, and at the same time successfully combines direct visualization, high sensitivity, and radiation-free nuclear magnetic imaging diagnosis with high selectivity and high curative effect. Infrared photodynamic therapy is fused together, and only a simple coordination self-assembly can achieve two functions of diagnosis and treatment at the same time, effectively combining diagnosis and treatment, reducing the complexity of preparation, and improving diagnosis and treatment. efficiency.

Description

technical field [0001] The invention belongs to the technical field of self-assembly nano-biomedicine, and specifically relates to a tumor microenvironment-responsive self-assembly diagnosis and treatment integration reagent and a preparation method thereof. Background technique [0002] Cancer is one of the chief culprits of killing human life. Many people talk about cancer, and the fight against cancer has never stopped. According to the latest data released by the American Cancer Center in 2017, there are currently 12 million newly diagnosed cancer cases and more than 7 million deaths each year, and the morbidity and mortality are still rising year by year. What is more serious is that cancer patients are gradually tend to be younger. Therefore, the development of non-toxic, efficient and personalized diagnosis and treatment integration reagents is an effective way to improve the efficiency of tumor diagnosis and treatment, and will also play a positive role in human dev...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K49/18A61K41/00A61K47/69A61K49/08A61K49/12A61K49/14A61P35/00
CPCA61K41/0057A61K41/0071A61K49/085A61K49/126A61K49/146A61K49/1833A61K47/6935A61P35/00
Inventor 杨洪雨付雁刘长玲佀庆波宋岩
Owner JILIN JUNTONGXING BIOTECH
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