Preparation method and application of a dual-target acid-sensitive Prussian blue drug-loading system

A Prussian blue and acid-sensitive technology, which is applied in the field of preparation of targeted drug delivery systems, can solve problems such as drug resistance, and achieve the effects of simple and mild preparation methods, enhanced chemotherapy effects, and easy release

Active Publication Date: 2022-06-03
SOUTHEAST UNIV
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  • Abstract
  • Description
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Problems solved by technology

Second, this interaction makes it acquire adhesion, migration and anti-apoptotic signals, leading to the occurrence of drug resistance

Method used

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  • Preparation method and application of a dual-target acid-sensitive Prussian blue drug-loading system
  • Preparation method and application of a dual-target acid-sensitive Prussian blue drug-loading system
  • Preparation method and application of a dual-target acid-sensitive Prussian blue drug-loading system

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[0031] The invention is a preparation method of an acid-sensitive Prussian blue drug-loading system modified by double targeting of CXCR4 antagonistic polypeptide and hyaluronic acid, comprising the following steps:

[0032] The technical solution is that, firstly, acid-sensitive polyethylene glycol-polyethyleneimine molecules are adsorbed on the surface of Prussian blue nanoparticles through electrostatic and hydrogen bonding interactions; secondly, CXCR4 antagonistic polypeptide E5 and hyaluronic acid bind to Prussian blue nanoparticles through chemical bonds. The polyethylenimine molecules on the surface of blue nanoparticles are connected; again, daunorubicin is loaded on the surface of Prussian blue nanoparticles through hydrogen bonding ( figure 1 ).

[0033] The preparation method comprises the following steps:

[0034](1) Preparation of Prussian blue nanoparticles (PBNPs): using potassium ferricyanide as raw material, using polyvinylpyrrolidone as reducing agent and s...

Embodiment 1

[0049] Preparation of Prussian Blue Nanoparticles

[0050] 131.7 mg of potassium ferricyanide and 3 g of polyvinylpyrrolidone K30 were weighed and dissolved in 40 mL of hydrochloric acid with a concentration of 0.01 M, and dissolved by magnetic stirring. After the reaction, the obtained blue solution was centrifuged at 10,000 rpm for 1 hour, and the precipitate was washed once with water, twice with ethanol, and once with water, and vacuum-dried at 55°C for 24 hours. The dried Prussian blue nanoparticles ( PBNPs) were collected and placed in a 4°C refrigerator for later use.

Embodiment 2

[0052] Preparation of acid-sensitive polyethyleneimine-polyethylene glycol modified Prussian blue nanoparticles

[0053] Precisely weigh a certain amount of PBNPs and polyethyleneimine-polyethylene glycol, all of which are prepared into an aqueous solution with a concentration of 0.5 mg / mL, and the nanoparticles are uniformly dispersed by ultrasound with the probe. Under magnetic stirring, 30 mL of PBNPs was added dropwise to 15 mL of polyethyleneimine-polyethylene glycol solution, and stirring was continued for 0.5 h. After stirring, excess HA was removed by ultrafiltration, and washed three times with pure water. The purified polyethyleneimine-polyethylene glycol-modified Prussian blue nanoparticles (PP-PBNPs) were prepared into an aqueous solution of 0.5 mg / mL, and stored in a refrigerator at 4°C for later use.

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Abstract

The invention discloses a preparation method and application of a dual-target acid-sensitive Prussian blue drug-carrying system, which can effectively solve the problems of leukemia drug resistance and liver and spleen infiltration. The technical solution is, firstly, the acid-sensitive polyethylene glycol-polyethyleneimine polymer is adsorbed on the surface of Prussian blue nanoparticles through electrostatic and hydrogen bonding; secondly, CXCR4 antagonistic polypeptide (E5) and hyaluronic acid are chemically bonded to Polyethyleneimine molecules on the surface of Prussian blue nanoparticles are connected; again, daunorubicin is adsorbed on the surface of Prussian blue nanoparticles through hydrogen bonding. The preparation method of the present invention is simple and mild, the material is safe and easy to obtain, and has good biocompatibility. The prepared carrier has long-term blood circulation ability, tumor cell double-targeting ability, lysosome escape ability, and acid-sensitive drug release ability, and can effectively Enhance the therapeutic effect of leukemia in mice and inhibit the homing of bone marrow and the infiltration of liver and spleen.

Description

technical field [0001] The invention belongs to the field of nano-medicine, in particular to the preparation of a targeted drug delivery system for leukemia treatment. Background technique [0002] Acute myeloid leukemia is a malignant clonal disease, mainly manifested in the abnormal proliferation and differentiation of hematopoietic stem cells, leading to hematopoietic failure. Although traditional chemotherapy methods are widely used, drugs cannot improve the clinical prognosis of patients very well. Minimal residual disease and cell resistance are important factors for relapse, metastasis and low survival rate of leukemia patients. In addition, since hematological tumors do not have significant EPR (enhanced penetration and retention) effects, improving targeting is very important to reduce systemic toxicity in patients. Therefore, finding new targets, removing minimal residual lesions, and overcoming cell drug resistance have become major issues to be solved in the tre...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K41/00A61K33/26A61K31/704A61K47/02A61K47/60A61K47/61A61K47/62A61K47/69A61P35/02A61P35/04B82Y5/00
CPCA61K47/6929A61K47/62A61K47/61A61K47/60A61K47/02A61K41/0052A61K31/704A61K33/26A61P35/02A61P35/04B82Y5/00A61K2300/00
Inventor 张宇白慧媛马明顾宁
Owner SOUTHEAST UNIV
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