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Preparation method, activity and application of GO-PLL-RGDS/VEGF-siRNA targeted gene drug

A targeting and drug technology, applied in gene therapy, drug combination, organic active ingredients, etc., can solve the problems of low liposome loading efficiency, high cytotoxicity, low gene delivery efficiency, etc.

Inactive Publication Date: 2017-10-10
CAPITAL UNIVERSITY OF MEDICAL SCIENCES
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

For example, the cytotoxicity of PEI is relatively high; the loading efficiency of liposomes is low; most inorganic nanomaterials are hydrophobic, with poor stability and biocompatibility
In addition, the poor tumor targeting of non-viral vectors is also a key factor causing low gene delivery efficiency and large toxic side effects in vivo

Method used

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  • Preparation method, activity and application of GO-PLL-RGDS/VEGF-siRNA targeted gene drug
  • Preparation method, activity and application of GO-PLL-RGDS/VEGF-siRNA targeted gene drug
  • Preparation method, activity and application of GO-PLL-RGDS/VEGF-siRNA targeted gene drug

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0080] Example 1 Preparation of GO-PLL-RGDS / VEGF-siRNA

[0081] Preparation of GO-PLL

[0082] Weigh 2.0mg of GO and ultrasonically disperse it in 4mL of ultrapure water, and use a probe sonicator, ie, a sonicator, to sonicate for 4h (2-second intermittent mode). Aqueous KOH (pH 9) was added to make up to 8 mL. Add 10.0 mg of PLL, at this time a precipitate is formed, continue to use KOH aqueous solution (pH11) to adjust the pH value to 9. The reaction bottle was placed in a 70°C oil bath and stirred for 24h. Stop heating after 24h, centrifuge (12000g, 20min), discard the supernatant, wash with water three times, and wash away unreacted PLL. Freeze-dried for later use. Measure the infrared spectrum. Fourier transform infrared spectroscopy (FTIR, Thermo Scientific TM Nicolet TM iS TM 5, cm -1 ): 3242.74, 2935.15, 1635.09, 1520.51, 1340.47, 1037.13, 601.35.

[0083] Preparation of Boc-Arg(Tos)-Gly-Asp(OMe)-Ser-OH

[0084] Boc-Arg(Tos)-Gly-Asp(OMe)-Ser-OBzl was prepa...

Embodiment 2

[0096] Example 2 Determination of the nanostructure of GO-PLL-RGDS and GO-PLL-RGDS / VEGF-siRNA

[0097] Experimental method Take 100 μL of GO, GO-PLL-RGDS aqueous dispersion with a concentration of 1000 μg / mL and dilute to 2 mL with pure water. The GO-PLL-RGDS / VEGF-siRNA aqueous dispersion was prepared according to the mass ratio of 10:1, that is, the concentration of GO-PLL-RGDS was 50 μg / mL, and the concentration of VEGF-siRNA was 5 μg / mL. 20 μL each was dropped onto a carbon support film (copper grid), and dried in an oven at 37°C for 24 hours. Each sample was observed under a transmission electron microscope (TEM, JEM-1230, JEOL, Japan) and photographs were taken. Then 20 μL of each was dropped onto the mica sheet, and left to air dry at room temperature. Each sample was observed under an atomic force microscope (AFM, VeecoInstruments, Inc, Plainview, USA) and photographs were taken. With water as blank background.

[0098] Experimental results from image 3 From the T...

Embodiment 3

[0099] Example 3 Determination of Zeta potential and hydrated particle size of GO-PLL-RGDS and GO-PLL-RGDS / VEGF-siRNA

[0100] Experimental method Prepare 100 μg / mL aqueous dispersion of GO and GO-PLL-RGDS for use. Prepare a GO-PLL-RGDS / VEGF-siRNA aqueous dispersion of 100 μg / mL (ie, the concentration of GO-PLL-RGDS is 100 μg / mL, and the concentration of VEGF-siRNA is 10 μg / mL). The particle size distribution and Zeta potential of the samples were measured with a laser particle size analyzer.

[0101] Experimental results The Zeta potential values ​​of GO, GO-PLL-RGDS and GO-PLL-RGDS / VEGF-siRNA were -40.59±2.23mV, 25.87±0.47mV, 15.36±2.62mV, respectively. The hydrated particle sizes of GO, GO-PLL-RGDS and GO-PLL-RGDS / VEGF-siRNA were 275.8±2.7nm, 162.9±4.5nm, 196.6±2.7nm, respectively. The zeta potential value changed from negative to positive, which further illustrates the successful modification of GO-PLL-RGDS. After loading VEGF-siRNA, the complex GO-PLL-RGDS / VEGF-siRNA s...

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Abstract

The invention discloses a delivery system GO-PLL-RGDS / VEGF-siRNA for delivering VEGF-siRNA, discloses a delivery carrier and a preparation method of the delivery system, discloses its nanostructure, discloses the cell uptake of the delivery system, discloses The effect of the delivery system on silencing VEGF gene is disclosed, its efficiency of down-regulating VEGF expression is disclosed, its effect on inhibiting tumor cell proliferation is disclosed, and its effect on inhibiting tumor growth in mice bearing S180 sarcoma and tumor targeting of the delivery system are disclosed effect. Therefore, the application of this gene delivery system in anti-tumor gene therapy drugs is clarified.

Description

technical field [0001] The present invention relates to the delivery system GO-PLL-RGDS / VEGF-siRNA A for delivering VEGF-siRNA, to its preparation method, to its nanostructure, to its cellular uptake, to its effect on silencing VEGF gene, Involves its efficiency of down-regulating VEGF expression, its ability to inhibit tumor cell proliferation, and its ability to inhibit tumor growth in mice bearing S180 sarcoma and the tumor-targeting effect of the delivery system, thus involving it as a non-viral carrier in the anti-tumor gene application in therapeutic drugs. It belongs to the field of biomedicine. Background technique [0002] In recent years, studies have found that in gene therapy of tumors, non-viral vectors are safer than viral vectors, avoiding the possibility of immunogenic reactions caused by viral vectors such as adenovirus, thus becoming a hot spot in gene delivery research. The reported non-viral vectors are mainly divided into cationic polymers (such as pol...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/51A61K47/04A61K47/18A61K47/34A61K31/7105A61K48/00A61P35/00
CPCA61K9/5115A61K9/5123A61K9/5146A61K31/7105
Inventor 崔纯莹任路路
Owner CAPITAL UNIVERSITY OF MEDICAL SCIENCES
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