Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Boron-doped tumor targeting drug and preparation method and application thereof

A tumor-targeting and drug-based technology, applied in the field of biomedicine, can solve problems such as low drug loading, strong systemic toxicity, and difficulty in meeting the treatment requirements of BNCT

Active Publication Date: 2021-08-31
THE NAT CENT FOR NANOSCI & TECH NCNST OF CHINA
View PDF4 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] As an important member of BNCT therapy, boron-containing drugs have not performed satisfactorily in clinical applications, because BNCT requires drugs to target tumors and accumulate sufficient boron-containing drugs in tumor cells. The ratio of the concentration in normal tissue or blood should be greater than 3.0, entering the concentration of each gram of tumor 10 The average amount of B is required to be 20-35 μg, and corresponds to a tumor cell containing at least 10 9 indivual 10 B atoms, but existing technologies such as the two BNCT drugs currently approved by the FDA, BSH (mercapto polyhedral boron clathrate) and BPA (4-boron-L-phenylalanine), cannot reach this level, and various boron loadings Targeted drugs such as low molecular weight borides, boron-doped peptides, antibody fragments and various proteins, intact antibodies and antibody-based conjugates, and liposomes, etc., are also due to low drug loading, poor penetration, and systemic Problems such as strong toxicity are difficult to meet the treatment requirements of BNCT
[0004] CN106279231A discloses a boron-containing compound used in BNCT and its preparation method and application. The new boron-containing compound provided by the invention is obtained through condensation, ammonolysis and ring-forming reactions, and is easy to prepare, low in cost, and has good biological properties. Its performance is superior to BPA in the uptake, accumulation and retention of tumor cells, and it has good application prospects in BNCT. It is also expected to become a clinical potential positron emission tomography tumor imaging agent. The identification of diseases and the detection of metastatic lesions in the whole body have created favorable conditions, but the boron-containing compounds are still not ideal in terms of tumor cell targeting and accumulation
However, this preparation needs the help of an external magnetic field to target it to the tumor site, and there may be problems such as low drug loading and poor penetration.

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Boron-doped tumor targeting drug and preparation method and application thereof
  • Boron-doped tumor targeting drug and preparation method and application thereof
  • Boron-doped tumor targeting drug and preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0074] This embodiment provides a boron-doped tumor targeting drug, which includes a polypeptide, a hydrophobic molecule 2-naphthaleneacetic acid at the nitrogen terminus of the polypeptide, and BSH linked to the lysine of the polypeptide; the polypeptide includes phosphorylated L-tyrosine , L-lysine and L-phenylalanine, the molecular structures of which are as follows:

[0075]

[0076] Its preparation method comprises the following steps:

[0077] (1) in the solid phase synthesis tube, 1.0g of 2-chloro-trityl chloride resin was swollen in 10mL of dichloromethane for 30min;

[0078] (2) using the phosphorylated L-tyrosine protected by Fmoc, L-phenylalanine, terminal amino and side chain amino groups by Fmoc and Boc protected L-lysine as raw materials, according to the above-mentioned polypeptide 1.0g of Fmoc and Boc-protected L-lysine and 992μL of N,N-diisopropylethylamine were dissolved in 5mL of N,N-dimethylformamide, and then added to the carrier resin. Nitrogen, reac...

Embodiment 2

[0090] The cumulative performance test of the boron-doped tumor targeting drug and BSH prepared in Example 1 was carried out in HeLa cells, and the specific method was as follows:

[0091] HeLa cells were selected as model cells, seeded with 2 × 10 5 Add 2 mL of DMEM medium containing 10-1000 μM product of Example 1 or 2 mL of DMEM medium containing 10-1000 μM BSH to a 6-well plate with 1000 μM of cells, respectively, and add 2 mL of DMEM medium containing 10-1000 μM BSH, respectively, and heat them at 37°C and 5% CO. 2 Incubate for 24h under the conditions. The cells were digested with trypsin, counted, and heated to digest by adding nitric acid. Finally, the amount of accumulated boron was measured by ICP-MS. The statistical results are as follows: Figure 4 shown.

[0092] Depend on Figure 4 It can be seen that the accumulative boron amount of the boron-doped tumor targeting drug of the present invention in HeLa cells is significantly greater than that of the BSH group ...

Embodiment 3

[0094] The cytotoxicity test of the boron-doped tumor targeting drug and BSH prepared in Example 1 is as follows:

[0095] HeLa cells were selected as model cells, and 0.1 mL of the product of Example 1 containing 10-1000 μM or 0.1 mL of DMEM medium containing 10-1000 μM BSH were added to a 96-well plate seeded with 5000 cells, and incubated at 37°C and 5 %CO 2 Under the same conditions, incubate for 24h, and then detect the cytotoxicity by MTT method. The statistical results are as follows Figure 5 shown.

[0096] Depend on Figure 5 It can be seen that the boron-doped tumor targeting drug involved in the present invention has almost no cytotoxicity to HeLa cells in the range of 10 μM-500 μM, indicating that the boron-containing drug has good biocompatibility and no systemic toxicity.

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

The invention relates to a boron-doped tumor targeting drug and a preparation method and application thereof. The boron-doped tumor targeting drug comprises polypeptide, hydrophobic molecules located at the nitrogen terminal of the polypeptide and a mercaptododecaborane disodium salt located on polypeptide lysine, wherein amino acids forming the polypeptide comprise phosphorylated L-tyrosine, L-lysine and L-phenylalanine. The drug can achieve specific enrichment in tumor cells, the enrichment amount of each tumor cell can reach 37.3 * 10<9> B atoms, and the boron neutron capture treatment demand is met. In addition, the boron-doped drug is good in biocompatibility and low in immunogenicity and toxicity.

Description

technical field [0001] The invention belongs to the technical field of biomedicine, in particular to a boron-doped drug and a preparation method and application thereof, in particular to a boron-doped tumor targeting drug and a preparation method and application thereof. Background technique [0002] Boron neutron capture therapy (BNCT) is a treatment that destroys cancer cells through nuclear fission reactions within tumor cells. By injecting boron-containing compounds, it accumulates in tumor cells, and is rarely distributed in other tissues. When irradiated with an epithermal neutron ray, boron-10 in cancer cells can capture neutrons to form unstable isotopes, and then nuclear fission occurs, releasing a very lethal ray that kills cancer cell. [0003] As an important member of BNCT therapy, boron-containing drugs are not satisfactory in clinical application, because BNCT requires drugs to target tumors and accumulate sufficient boron-containing drugs in tumor cells. T...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
IPC IPC(8): A61K41/00A61K47/64A61P35/00
CPCA61K41/0095A61K47/64A61P35/00Y02P20/55
Inventor 姚庆鑫高远
Owner THE NAT CENT FOR NANOSCI & TECH NCNST OF CHINA
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com