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Targeted nanomedicine for overcoming drug resistance caused by tumor hypoxia based on MRI guidance and its preparation method and application

An imaging-guided, nano-drug technology, applied in the field of biomedicine, can solve the problems of short metabolic lifespan of small molecule drugs, poor targeting of SeD-1b, and lack of recognition ability, so as to overcome the problem of drug resistance and achieve good targeting. , the effect of cheap treatment of cancer

Active Publication Date: 2022-07-12
JINAN UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, although SeD-1b is obviously superior to traditional anti-BCa drugs, it also has the following disadvantages: 1. SeD-1b is a chemical small molecule drug, which is usually dispersed and adsorbed to the bladder cancer site in a free diffusion manner. Short metabolic lifespan leads to poor targeting of SeD-1b; 2. Due to the special structure of the bladder, drugs that reach the tumor site are easily diluted and cleared by urine; 3. Although SeD-1b has a certain stability in the urine environment However, the solubility still needs to be improved; 4. Although SeD-1b itself has fluorescence, its luminescence ability is weak, and it cannot be used as a positioning agent for diagnosis, nor does it have the ability to identify it in enhanced imaging examinations, so it cannot Serving the curative effect monitoring of BCa, reducing the pain of patients undergoing cystoscopy
[0006] However, there is no targeted nano-drug that can not only overcome the drug resistance caused by tumor hypoxia, but also monitor the tumor treatment process in real time.

Method used

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  • Targeted nanomedicine for overcoming drug resistance caused by tumor hypoxia based on MRI guidance and its preparation method and application
  • Targeted nanomedicine for overcoming drug resistance caused by tumor hypoxia based on MRI guidance and its preparation method and application
  • Targeted nanomedicine for overcoming drug resistance caused by tumor hypoxia based on MRI guidance and its preparation method and application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0076] Example 1: Preparation of targeted nanomedicine

[0077] (1) Preparation of raw materials:

[0078] 1) Preparation of 3.5 mM Tween-80: Weigh 5 g of Tween-80, and use 1 L of secondary water to prepare an aqueous solution of Tween-80 with a concentration of 3.5 mM.

[0079] 2) Prepare 1.05mM Fe 3 O 4 Nanoparticle-acetone dispersion: Weigh 0.2436g Fe 3 O 4 The nanoparticles were dispersed in 1L of acetone.

[0080] 3) Preparation of 20 mM PLGA-acetone dispersion: Weigh 20 g of PLGA (lactic acid LA: glycolic acid GA=50:50, Mn=13000) and disperse it in 1 L of acetone.

[0081] 4) Preparation of 0.65 mM SeD-1b solution: Weigh 24.375 mg of SeD-1b (SeD-1b is prepared according to Example 1 in the patent "201610127128.3") and dissolve it in 10 mL of dimethyl sulfoxide.

[0082] 5) Preparation of 20 mg / mL PLZ4 solution: Weigh 20 g of polypeptide PLZ4 powder and dissolve it in 1 L of phosphate buffered saline (PBS) with a pH of 7.4 and a concentration of 0.01 M.

[0083] (2...

Embodiment 2

[0110] Example 2: In vitro stability study of targeted nanomedicines

[0111] The preparation method of the targeted nanomedicine PLZ4@SeD nanoparticles used in this example is the same as the preparation method described in Example 1 of this application.

[0112] The mixed solutions for detecting the particle size of nanomedicine PLZ4@SeD nanoparticles were prepared according to the following methods:

[0113] Group A1: 1 mL of dialyzed PLZ4@SeD nanoparticle aqueous solution was mixed with pH=5.6, 0.01M phosphate buffer at a volume ratio of 1:2;

[0114] Group A2: 1 mL of dialyzed PLZ4@SeD nanoparticle aqueous solution was mixed with DMEM medium with pH=5.6 adjusted with hydrochloric acid in a volume ratio of 2:1;

[0115] Group B1: 1 mL of dialyzed PLZ4@SeD nanoparticle aqueous solution was mixed with pH=7.4, 0.01M phosphate buffer at a volume ratio of 2:1;

[0116] Group B2: 1 mL of dialyzed PLZ4@SeD nanoparticle aqueous solution was mixed with pH=7.4 DMEM medium at a vol...

Embodiment 3

[0119] Example 3: Comparison of in vitro antitumor activity of targeted nanomedicines

[0120] The preparation method of the targeted nanomedicine PLZ4@SeD nanoparticles used in this example is the same as the preparation method described in Example 1 of this application.

[0121] Take the density of growth in logarithmic phase as 2×10 4 cells / mL of bladder cancer EJ cells, bladder cancer J82 cells, bladder cancer T921 cells, breast cancer MCF-7 cells, and liver cancer cells HepG2 cells were seeded in 96-well plates, 100 μL per well; Then, 100 μL of Fe diluted in DMEM medium was added to the first group of wells containing bladder cancer EJ cells, bladder cancer J82 cells, bladder cancer T921 cells, breast cancer MCF-7 cells, and liver cancer cells HepG2 respectively. 3 O 4 nanoparticles so that the final concentration is 0.08mmol / L. without Fe 3 O 4 Nanoparticles of bladder cancer EJ cells, bladder cancer J82 cells, bladder cancer T921 cells, breast cancer MCF-7 cells an...

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Abstract

The invention discloses a targeted nanomedicine for overcoming drug resistance caused by tumor hypoxia based on nuclear magnetic imaging guidance, a preparation method and application thereof, and belongs to the technical field of biomedicine. The preparation method of the targeted nanomedicine includes the following steps: S1. Disperse PLGA, a nuclear magnetic imaging contrast agent and an antitumor drug in an organic solvent, respectively, then add a surfactant, and obtain solution A after stirring and dialysis; S2. Use NHS and EDC to activate the carboxyl group of solution A to obtain an activated solution A; S3. Add targeting molecules to the above activated solution A, and after stirring and dialysis, MRI-guided anti-tumor hypoxia can be obtained Targeted nanomedicines causing drug resistance. The targeted nanomedicine PLZ4@SeD nanoparticle of the present invention has better therapeutic effect than clinical medicines such as doxorubicin, mitomycin and pirarubicin under the condition of hypoxia.

Description

technical field [0001] The invention belongs to the technical field of biomedicine, and in particular relates to a targeted nanomedicine for overcoming drug resistance caused by tumor hypoxia based on nuclear magnetic imaging guidance, and a preparation method and application thereof. Background technique [0002] Bladder cancer (BCa) is the urinary system tumor with the highest incidence in my country. According to statistics, there were nearly 550,000 new cases worldwide in 2018. In the conventional treatment regimen for bladder cancer, in addition to transurethral resection of bladder tumor (TURBT) for non-muscle-invasive BCa (NMIBC) and radical total cystectomy for muscle-invasive BCa (MIBC), Drug therapy is an important part of intravesical infusion therapy, systemic chemotherapy, and local interventional chemotherapy after TUR. However, in the process of using anti-BCa drugs, infusion drugs have poor sensitivity, unstable function, high cost, and large toxic and side e...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K49/18A61K49/12A61K9/51A61K47/34A61K47/42A61K45/00A61K31/704A61P35/00
CPCA61K49/1857A61K49/12A61K9/5153A61K9/5169A61K45/00A61K31/704A61P35/00
Inventor 陈填烽林伟强曾钦松刘宏星
Owner JINAN UNIVERSITY
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