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Self-assembly method based on amino acid and near-infrared dye and anti-tumor application

A near-infrared dye and self-assembly technology, which is applied in the direction of antineoplastic drugs, medical preparations containing active ingredients, drug combinations, etc., can solve the problems of non-reactive release, complex synthesis, limited application, etc., to achieve commercialization, Enhance the effect of accumulation

Pending Publication Date: 2022-05-17
CHONGQING MEDICAL UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the application of these NO release strategies remains limited, which often involve complex synthesis, unresponsive release, and lack of specific targets, leading to excess harmful NO in normal tissue blood vessels.

Method used

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  • Self-assembly method based on amino acid and near-infrared dye and anti-tumor application
  • Self-assembly method based on amino acid and near-infrared dye and anti-tumor application
  • Self-assembly method based on amino acid and near-infrared dye and anti-tumor application

Examples

Experimental program
Comparison scheme
Effect test

example 1

[0056] Synthesis of FL@IR783 under acidic conditions in Example 1:

[0057] Take 200μL IR783 (10mM, DMSO) and add it dropwise to 2mL Fmoc-L-arginine (FL) (5mg / mL, 0.05MHCl) solution, stir and react for 1h, centrifuge at 5000rpm for 10min, wash with ultrapure water 3 times Finally, the product was collected and dispersed in 1 / 10000 triethylamine aqueous solution or NaOH solution or PBS. The final nanocomposites were detected by TEM. FL@IR783 exhibits a fusiform shape (~70 nm) in triethylamine solution and PBS solution. Furthermore, FL@IR783 in NaOH solution is uniformly distributed spherical (~250 nm).

example 2

[0058] Synthesis of FL@IR783 under neutral conditions in Example 2:

[0059] Take 200 μL IR783 (10mM, DMSO) solution and add dropwise to 1.7mL H 2 In O, take 100 μL FL (60mM, DMSO) and slowly add it dropwise to the above solution. After rapid stirring for 2h, centrifuge at 5000rpm for 10min, wash with ultrapure water for 3 times, collect the product and disperse it in H 2 O (pH ~ 6) or H 2 O (pH ~ 7) or PBS (pH ~ 7.4). FL@IR783 dispersed in three different solutions contained characteristic absorption peaks of FL and IR783, respectively, detected by UV-spectrophotometer.

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Abstract

Compared with the traditional tumor treatment method, the gas therapy as an emerging and promising cancer treatment method is widely concerned. Although a few NO donors have obtained certain effects in the aspect of tumor treatment at present, the NO release strategies are still limited in application and even bring a lot of side effects. According to the present invention, the endoplasmic reticulum-targeted self-assembly multifunctional nano-composite FL (at) IR783 using Fmoc-L-arginine (Fmoc-L-Arg,) as the NO precursor is designed, such that the endoplasmic reticulum-targeted self-assembly multifunctional nano-composite FL (at) IR783 is provided; firstly, IR783 is endocytosed by tumor cells to reach ER in a targeted mode, then IR783 generates a large amount of ROS mainly containing < 1 > O2 under excitation of near infrared rays, and guanidyl of L-arginine is induced to be oxidized to generate NO. NO released in cells can inhibit activation of tumor-related platelets, enhance vascular permeability, increase accumulation of nanoparticles in tumors and improve the anti-tumor effect on one hand; on the other hand, unnecessary systematic bleeding can be prevented. In-vitro experiments show that FL at IR783 is mainly gathered on endoplasmic reticulum in cells, after near-infrared laser irradiation, not only is endoplasmic reticulum stress caused, but also generated < 1 > O2 is utilized to induce generation of NO, and then growth of tumor cells is inhibited. In a word, the research result shows that the multifunctional nano-composite has good application potential in tumor treatment.

Description

technical field [0001] The invention relates to a preparation method for self-assembly of amino acids and near-infrared dyes to form a multifunctional nanometer treatment system. Specifically, it relates to a nanocomposite that utilizes amino acids and near-infrared dyes to self-assemble and disperse in different solvents to form different states. Moreover, the nanocomposite can be used for drug delivery and tumor treatment, and belongs to the fields of nanomaterials and regenerative medicine. Background technique [0002] Gas therapy has received a lot of attention as an emerging and promising approach to cancer treatment. Nitric oxide (NO), synthesized by the nitric oxide synthase (NOS) enzyme, acts as a key signaling molecule in various physiological and pathological processes. NO has been found to play an important role in the cardiovascular system, respiratory system, nervous system, immune system, antibacterial therapy, wound healing and other biomedical fields, espe...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/198A61K33/00A61P35/00A61P17/02A61P9/10A61K49/00
CPCA61K31/198A61K33/00A61P35/00A61P17/02A61P9/10A61K49/0032A61K49/0093Y02P20/55
Inventor 阳章友冷凤陈璐
Owner CHONGQING MEDICAL UNIVERSITY