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Triple-negative breast cancer targeted drug carrier and preparation and application thereof

A triple-negative breast cancer and drug technology, applied in the field of medicine, can solve the problems of side effects and no TNBC targeted therapy drugs, etc., and achieve excellent targeting ability, molecular weight and reaction process controllable, good hydrophobic drug carrying capacity Effect

Active Publication Date: 2020-08-11
JIANGSU PROVINCE HOSPITAL THE FIRST AFFILIATED HOSPITAL WITH NANJING MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0002] Triple negative breast cancer (TNBC) is a highly malignant tumor. Currently, there is no targeted therapy for TNBC in clinical practice.
These chemotherapeutics are characterized by off-target distribution in TNBC treatment and can cause severe side effects

Method used

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  • Triple-negative breast cancer targeted drug carrier and preparation and application thereof
  • Triple-negative breast cancer targeted drug carrier and preparation and application thereof
  • Triple-negative breast cancer targeted drug carrier and preparation and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0041] SCL1A5 Gene Expression in Example 1 Breast Cancer and Different Types

[0042] Through the Cancer Genome Atlas (TCGA) data portal, query and obtain the data of SLC1A5 gene and breast cancer. The survival period of breast cancer patients and the expression of SLC1A5 gene in different types of breast cancer were found by analyzing the data. First, the clinical data of breast cancer patients and the corresponding expression level of SLC1A5 transcriptome were analyzed, including 113 normal human breast tissue samples and 5 breast cancer subtypes. Among them, 449 cases were luminal A type, 181 cases were luminal B type, 69 cases were HER2 positive, 166 TNBC Basal-like samples and 33 TNBC Normal-like samples were based on PAM50 intrinsic breast cancer subtypes. In order to analyze the differences in gene expression of SLC1A5 in patients with various subtypes of breast cancer, the expression data of SLC1A5 corresponding to the patients, that is, fragments per kilobase million...

Embodiment 2

[0049] The synthesis of embodiment 2 Gln-PEG-b-PAE copolymer

[0050] Design and synthesis of PEG-b-PAE by Michael addition reaction, then coupling glutamine to NH2-PEG-b-PAE copolymer by DCC / DMAP to obtain pH-responsive drug delivery carrier gln-PEG-b-PAE The copolymer realizes its function of targeting TNBC, and the specific synthesis process is as follows.

[0051] (1) Synthesis of Fmoc-PEG-b-PAE

[0052] Take Fmoc-protected PEG 1000 (0.1mmol) was dissolved in 10mL of anhydrous dichloromethane, and 2 times the equivalent of triethylamine was added, and then the reaction bottle was placed in cold hydrazine at 0°C, and acryloyl chloride (0.5mmol, aladdin, Shanghai, China) and stirred in cold hydrazine for 2 h. Subsequently, the reaction bottle was taken out to return the solution to room temperature and stirred for 24 h. After the reaction was completed, it was washed with dilute hydrochloric acid and concentrated in vacuo to obtain Fmoc-protected polyethylene glycol meth...

Embodiment 3

[0060] The synthesis of embodiment 3 Gln-PEG-b-PAE copolymer

[0061] Design and synthesis of PEG-b-PAE by Michael addition reaction, then coupling glutamine to NH2-PEG-b-PAE copolymer by DCC / DMAP to obtain pH-responsive drug delivery carrier gln-PEG-b-PAE The copolymer realizes its function of targeting TNBC, and the specific synthesis process is as follows.

[0062] (1) Synthesis of Fmoc-PEG-b-PAE

[0063] Take Fmoc-protected PEG 5000 (0.2mmol) was dissolved in 20mL of anhydrous dichloromethane, and 2 times the equivalent of triethylamine was added, and then the reaction bottle was placed in cold hydrazine at 0°C, and acryloyl chloride (0.4mmol, aladdin, Shanghai, China) and stirred in cold hydrazine for 2 h. Subsequently, the reaction bottle was taken out to return the solution to room temperature and stirred for 24 h. After the reaction was completed, it was washed with dilute hydrochloric acid and concentrated in vacuo to obtain Fmoc-protected polyethylene glycol meth...

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Abstract

The invention discloses a triple-negative breast cancer targeted drug carrier and preparation and application thereof. The carrier has the structure as shown in a formula (1), and is a block copolymerGln-PEG-b-PAE obtained by coupling glutamine with polyethylene glycol-poly(beta-amino ester), wherein the carrier is subjected to synthesis through a Michael addition reaction to obtain a polyethylene glycol-poly(beta-amino ester) block copolymer PEG-b-PAE, then an amidation reaction is performed to enable the carboxyl terminus of glutamine Gln to be coupled to the PEG-b-PAE, the targeted drug carrier and hydrophobic TNBC resisting medicines of adriamycin and the like can be self-assembled to prepare a micelle agent, a pH resonance tumor targeted drug delivery system is formed, and a new targeted therapy method is provided for TNBC treatment.

Description

technical field [0001] The invention belongs to the field of medicine, and in particular relates to a triple-negative breast cancer (TNBC) targeting drug carrier and a preparation method and application thereof. Background technique [0002] Triple negative breast cancer (TNBC) is a highly malignant tumor, and currently there is no targeted therapy for TNBC in clinical practice. The clinical treatment of TNBC is mainly based on chemotherapy, and drugs such as doxorubicin (DOX) and paclitaxel are commonly used. These chemotherapeutic drugs have the characteristics of non-targeted distribution in the treatment of TNBC, which can cause severe side effects. Therefore, the development of new targeted therapeutic strategies against TNBC is imminent. [0003] Amino acids play an important role in the growth, invasion and metastasis of TNBC. Among them, glutamine is particularly related to the growth and metabolism of TNBC. SLC1A5 is an important glutamine transporter. Studies h...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/34A61K9/107A61P35/00C08G73/06
CPCA61K47/34A61K9/1075A61P35/00C08G73/0627
Inventor 张薇吴旸邓飞唐文娟徐迪刘镇王丹丹朱益智丁永斌唐金海
Owner JIANGSU PROVINCE HOSPITAL THE FIRST AFFILIATED HOSPITAL WITH NANJING MEDICAL UNIV