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Antibody, polypeptide and nucleic acid combined treatment targeting carrier as well as preparation method and application thereof

A therapeutic target and carrier technology, applied in the direction of antibody medical components, antibodies, drug combinations, etc., can solve the problems of high toxicity, difficult to safely and effectively inhibit tumor growth and metastasis, and achieve the effect of preventing leakage

Active Publication Date: 2018-12-28
SHANGHAI JIAO TONG UNIV +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] HER2-positive breast cancer, as a type with poor prognosis, needs to receive combination therapy based on HER2-targeted therapy. Combination therapy with anti-HER2 monoclonal antibody Herceptin combined with chemotherapy drugs such as paclitaxel is highly toxic and difficult to be safe and effective The growth and metastasis of tumors can be effectively inhibited. Current studies have shown that the anti-apoptosis gene survivin gene in HER2-positive breast cancer cells is overexpressed. increase

Method used

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  • Antibody, polypeptide and nucleic acid combined treatment targeting carrier as well as preparation method and application thereof
  • Antibody, polypeptide and nucleic acid combined treatment targeting carrier as well as preparation method and application thereof
  • Antibody, polypeptide and nucleic acid combined treatment targeting carrier as well as preparation method and application thereof

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preparation example Construction

[0049] The present invention relates to a method for preparing the above-mentioned antibody, polypeptide and nucleic acid combination therapy targeting carrier, comprising the following steps:

[0050] a. Connection reaction between Herceptin and hyaluronic acid (HA)

[0051] Herceptin is a commercially available human injection, and the excipients in it are removed by ultrafiltration in a 100k ultrafiltration centrifuge tube: L-histidine hydrochloride and L-histidine, because histidine is also a basic amino acid. The response is disturbed. The concentration after ultrafiltration is 17.6mg / ml (9.51×10 -5 mol / L). Each molecule of Herceptin contains 44 histidines. The specific experimental steps are as follows: activation of carboxyl groups, pH 6.0 MES buffer solution, HA, N-hydroxysuccinimide (NHS), + 1-(3-dimethylaminopropyl)-3-ethylcarbodi The molar concentrations of imine hydrochloride (EDC) were 0.2mM, 5mM, and 2mM respectively, and the reaction was activated at room te...

Embodiment 1

[0055] Example 1, Preparation method of antibody, polypeptide and nucleic acid combination therapy targeting carrier

[0056] Such as figure 1As shown, the system for measuring the physicochemical properties of antibody, polypeptide and nucleic acid combination therapy targeting carrier is carried out in aqueous solution. After mixing the cationic liposomes and polypeptides in different mass ratios, they are added into the nucleic acid aqueous solution and continue to mix evenly. In the specific experiment, the mass ratios of cationic liposomes, polypeptides and nucleic acids were 1:8:1, 1:4:1 and 1:2:1, respectively, and incubated at room temperature for 30 minutes, and then different proportions of HA- HER was added to the mixture and mixed well, and the mass ratio of HA to DNA or siRNA in HA-HER was 10:1:8:1, 14:1:4:1 and 30:1:2:1 respectively. Set aside for 10-25 minutes. For the carrier system used in cell experiments, serum-free medium can be used instead of ultrapure...

Embodiment 2

[0057] Example 2, Zeta Potential of Antibody, Polypeptide and Nucleic Acid Combination Therapy Targeting Carrier

[0058] Zetasizer 2000 was used to measure the surface charge of the complex, the sample measurement time was set to automatic, each sample was measured 3 times, and the average value was plotted. The results of the zeta potential measurement of the complex are shown in Table 1. It can be seen from Table 1 that when hyaluronic acid is used as the shell shielding charge, the potential potential of nanoparticle HLPR is negative charge -38 mV, and when HA-HER is used as shell shielding charge, the zeta potential of nanoparticle AHLPR is close to neutral charge (-12 mV). On this basis, we selected HA-HER with a mass ratio of hyaluronic acid to siRNA of 14:1 as the shell to assemble nanocarriers for research.

[0059] Table 1

[0060]

[0061] Table 1 shows the particle size and zeta potential of the targeted carrier AHLPR and the corresponding control group HLPR a...

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Abstract

The invention discloses an antibody, polypeptide and nucleic acid combined treatment targeting carrier as well as a preparation method and an application thereof and mainly solves the technical problems of defects in existing in-vivo conveying technologies of macromolecular drugs. The targeting carrier is biological macromolecular drug conveying nanoparticles having negative charge or electric neutrality on the surface and containing targeting groups; an inner core of the targeting carrier is formed by polypeptide and nucleic acid; the antibody, polypeptide and nucleic acid combined treatmenttargeting carrier has a shell formed by sequential dense covering and wrapping of irregular cation lipid membranes and polyanions, and the polyanions wrap the surfaces of the nanoparticles under the action of static electricity and hydrogen bonds.

Description

technical field [0001] The present invention relates to a biomacromolecule drug delivery technology in the field of pharmaceutical technology, in particular to the construction and construction of a non-viral vector system that can be used for system delivery of antibodies, polypeptides and nucleic acids (DNA, siRNA, microRNA and shRNA, etc.) The preparation technology specifically relates to a nanoparticle for targeted delivery of antibody, polypeptide and nucleic acid drug combination therapy. Background technique [0002] The proto-oncogene human epidermal growth factor receptor-2 (human epidermal growth factor receptor-2, HER2) gene, c-erbB-2 gene, is located on chromosome 17q12-21.32 and encodes a transmembrane receptor-like protein with a relative molecular mass of 185,000 Protein with tyrosine kinase activity. HER2 is an important prognostic factor for breast cancer. HER2-positive (overexpressed or amplified) breast cancer accounts for 20-25% of all breast cancer pat...

Claims

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Application Information

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IPC IPC(8): A61K9/51A61K47/36A61K47/24A61K47/61A61K39/395A61K38/17A61K31/7088A61P35/00
CPCA61K9/5123A61K9/5161A61K31/7088A61K38/1767A61K39/39558A61K47/61A61P35/00A61K2300/00
Inventor 杜子秀陈娟徐宇虹韩士永徐红岩竺剑峰
Owner SHANGHAI JIAO TONG UNIV
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