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Sorafenib-gene co-loaded nano-drug for cancer treatment as well as preparation method and application thereof

A nano-drug, cancer treatment technology, applied in gene therapy, drug combination, pharmaceutical formulation, etc., can solve the problem of lack of technical solutions, and achieve the improvement of reactive oxygen species level, good in vivo anti-tumor effect and biological safety, and efficient gene transfer. dyeing effect

Active Publication Date: 2021-01-26
ZHEJIANG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the level of reactive oxygen species in tumor cells is still not enough to cause the rapid and efficient release of reactive oxygen species-responsive nanogene drugs in cells, and there is no literature that discloses a feasible technical solution.

Method used

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  • Sorafenib-gene co-loaded nano-drug for cancer treatment as well as preparation method and application thereof
  • Sorafenib-gene co-loaded nano-drug for cancer treatment as well as preparation method and application thereof
  • Sorafenib-gene co-loaded nano-drug for cancer treatment as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0060] Example 1: Preparation and characterization of nanoaggregates with different N / P

[0061] Plasmid DNA (USP22 shRNA) was diluted with HEPES buffer solution (10 mM, pH=7.4) to a solution having a DNA concentration of 40 μg / mL. According to the preset N / P ratio (N / P=5, 9, 13, 17, 21, 25), B-PDEAEA was dissolved in HEPES buffer solution (10mM, pH=7.4) at the corresponding concentration to obtain different concentrations of B-PDEAEA solution. Then, equal volumes of plasmid DNA solutions were added to B-PDEAEA solutions of different concentrations, and the mixture was vortexed for 10 seconds immediately, and then left to stand for 30 minutes to obtain nano-aggregate solutions with different N / P ratios.

[0062] The particle size, zeta potential and morphology of the nano-aggregates were detected by dynamic light scattering and transmission electron microscopy. The particle size and zeta potential of the nanoaggregates ( figure 1 ) results show that the particle size of na...

Embodiment 2

[0063] Example 2: Detection of Gene Loading Efficiency and Active Oxygen Response Ability of Nanoaggregates with Different N / P Ratio

[0064] 1. Gel retardation experiments of nanoaggregates with different N / P ratios

[0065] Take 20 μL of nanoaggregate solutions with different N / P ratios prepared in Example 1, and take 0.4 μg of shUSP22 diluted to 20 μL with HEPES buffer solution (10 mM, pH=7.4) as a control. The above 7 samples were loaded on the agarose gel containing Gel Red with a mass volume fraction of 0.8%, and electrophoresed in TBE buffer at 120V for 45 minutes. After electrophoresis, the gel was placed in a UV imager for imaging.

[0066] Electrophoresis results ( image 3 ) shows that the active oxygen responsive polymer B-PDEAEA selected in Example 1 can efficiently compress plasmid DNA between N / P ratios of 5-25, and block the migration of DNA.

[0067] 2. Gel retardation experiment of nanoaggregates with different N / P ratios incubated in 200 μM hydrogen perox...

Embodiment 3

[0070] Example 3: Inhibition efficiency of different N / P ratio nanoaggregates on USP22 protein expression in Huh-7 liver cancer cell line

[0071]150,000 Huh-7 cells were seeded in 6-well plates. After culturing overnight, the nanoaggregates with different N / P ratios prepared in Example 1 were added to the cell culture medium, wherein the concentration of shUSP22 was 8 μg / well. Lipofectamine 2000 (Lipo2000) loaded with shUSP22 plasmid and branched polyethyleneimine (PEI, 25kDa) were set as positive controls, and the mixing ratio of Lipo2000 and plasmid was 2 μL:1 μg; the N / P of PEI and plasmid DNA was 7. After incubation for 48 hours, discard the medium, collect the cells with trypsin after washing with PBS solution, and add 100 μL of RIPA lysate containing protease inhibitors to the cell pellet. The protein concentration was quantified by BCA method and the corresponding volume of Loading buffer was added, followed by protein gel electrophoresis and membrane transfer. Accor...

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Abstract

The invention provides a sorafenib gene co-loaded nano-drug for cancer treatment as well as a preparation method and application thereof. The sorafenib gene co-loaded nano-drug comprises a nano-aggregate wrapped by a targeting lipid layer; the targeting lipid layer comprises sorafenib, phospholipid, a targeting substance and cholesterol; and the nano-aggregate is shUSP22 wrapped by an active oxygen response material. The preparation method comprises the following steps: coating shUSP22 with the active oxygen response material to prepare the nano-aggregate; and loading the targeting lipid layeron a surface of the nano-aggregate to obtain the sorafenib gene co-loaded nano-drug. The application is an application of the sorafenib gene co-loaded nano-drug in preparation of drugs for treating cancers. The sorafenib gene co-loaded nano-drug can effectively improve active oxygen level in cancer cells, inhibit expression of USP22 in liver cancer cells, efficiently kill the liver cancer cells,prolong blood circulation time of sorafenib and inhibit tumor growth.

Description

technical field [0001] The invention belongs to the technical field of antineoplastic drugs, and in particular relates to a sorafenib-gene co-loaded nano-medicine for cancer treatment and its preparation method and application. Background technique [0002] Hepatocellular carcinoma (HCC, hereinafter referred to as liver cancer) is the fourth most common malignant tumor in my country. Limited by the difficulty of early screening and early diagnosis of liver cancer and its complex biological mechanism, the current five-year survival rate of liver cancer patients is only 14%-18%. In recent years, with the development of molecular biology and pharmaceutical science of liver cancer, molecular targeted therapy targeting the proliferation, apoptosis, and angiogenesis of liver cancer has gradually received attention in the diagnosis and treatment of liver cancer. The advent of multikinase inhibitor-Sorafenib has prolonged the survival of liver cancer patients to a certain extent. ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/51A61K47/24A61K47/28A61K47/26A61K47/32A61K31/7105A61K31/44A61K48/00A61P35/00
CPCA61K9/5123A61K9/5138A61K9/5146A61K31/44A61K31/7105A61P35/00A61K2300/00
Inventor 徐骁申有青相佳佳许圣均凌孙彬单巧南
Owner ZHEJIANG UNIV
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