ATP responding type drug-releasing nano gel and preparation method thereof

A nanogel and drug technology, applied in the field of medicine, can solve the problems of normal tissue side effects and poor targeting of drug delivery systems, and achieve the effects of improving safety and targeting, reducing toxic and side effects, and improving therapeutic effects

Inactive Publication Date: 2017-11-17
CHINA PHARM UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] The purpose of the present invention is to overcome the property that nucleic acid aptamers are easily degraded by nucleases in vivo, and use carboxymethyl chitosan and polymer chains chemically synthesized by single-stranded DNA as carriers to protect aptamers from being degraded before re...

Method used

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  • ATP responding type drug-releasing nano gel and preparation method thereof
  • ATP responding type drug-releasing nano gel and preparation method thereof
  • ATP responding type drug-releasing nano gel and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

specific Embodiment 1

[0025] step 1:

[0026] Send the following 3 DNA oligonucleotide strands to the company for synthesis:

[0027] ATP aptamer: 5'-ACC TGG GGG AGT ATT GCG GAG GAA GGT-3'

[0028] DNA1: 5'-CTC TCT CTC TTT ACC TTC CTC CGC-3'

[0029] DNA2: 5'-ACT CCC CCA GGT AAA GAG AGA GAG-3'

[0030]Dissolve the single strands of DNA1 (100.76nmol) and DNA2 (71.86nmol) in 1mL of MES buffer (0.1M, pH4.9), and then add 1-ethyl-(3-dimethylaminopropyl)carbodiene Amine hydrochloride (1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride, EDC.HCL) and N-hydroxysuccinimide (N-hydroxysuccinimide, NHS), activated at room temperature for 2h, adding a certain amount of carboxymethyl Based on chitosan, shake at 1200rpm at room temperature for 24h, rinse with MES buffer (0.1M, pH 4.9), add 1mL of ammonia water (28%), and react for 24h at 40°C; take the supernatant and use a dialysis bag (MWCO: 1000 ) dialyzed for 16 hours; freeze-dried to obtain white flocculent powder CMCS-DNA1 and CMCS-DNA2. The s...

specific Embodiment 2

[0032] The ATP-responsive drug-releasing nanogel obtained in Example 1 of the present invention is investigated for ATP-responsive drug release, see attached image 3 .

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Abstract

The invention relates to an ATP responding type drug-releasing nano gel and a preparation method thereof, and belongs to the technical field of medicine. The nano gel is composed of carboxymethyl chitosan, DNA 1 with carboxyl modified terminals, DNA 2 with carboxyl modified terminals, and an ATP aptamer. Amino groups of carboxymethyl chitosan react with carboxyl groups of terminals of single chain DNA 1 and DNA2 to form stable amide bonds; because the ATP aptamer can carry out complementary base pairing with single chain DNA 1 and DNA2, the ATP aptamer can be used as a gel crosslinking agent, which can realize the crosslinking of nano gel; through physical embedding, doxorubicin hydrochloride is embedded in the GC segment of nucleic acid, the drug encapsulation is realized; and a novel ATP responding type drug-releasing nano gel drug delivering system is prepared. The system can respond to the high concentration ATP in tumor cell and competitively combines with the gel crosslinking agent (ATP aptamer); thus the complementarily paired nucleic acid chains are broken, the gel skeleton is broken, and drugs are released. The provided nano gel can improve the safety and targeting property of a tumor drug delivery system to a certain degree.

Description

technical field [0001] The invention relates to an ATP-responsive drug-releasing nanogel and a preparation method thereof, belonging to the technical field of medicine. Background technique [0002] Tumor is a global public health problem and has become one of the major threats to modern human health. The main methods of tumor treatment are surgery, chemotherapy, radiotherapy and cell therapy. Among them, chemotherapy is a common method for treating tumors. In recent years, chemotherapy has made great progress and prolongs the survival time of patients. However, chemotherapy is helpless for solid tumors that pose a greater threat to human health, and chemotherapy is inhibiting and eliminating hyperplasia. Due to the lack of selectivity of most anti-tumor drugs, they also inhibit other normal cells in the human body, causing side effects such as vomiting, nausea, hair loss, bone marrow suppression, chemotherapy-related cognitive impairment, and cardiotoxicity. Therefore, th...

Claims

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Application Information

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IPC IPC(8): A61K9/06A61K47/36A61K47/26A61K31/704A61P35/00
CPCA61K9/06A61K31/704A61K47/26A61K47/36
Inventor 吴正红赵美慧张钰
Owner CHINA PHARM UNIV
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