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Temperature targeting-based nanogel gene delivery compound, and preparation method and application thereof

A nanogel, gene delivery technology, applied in the field of medicine, can solve the problems of high immunogenicity, target cell damage, high technical and equipment requirements, etc., to improve the transfection efficiency and improve the effect of gene therapy.

Inactive Publication Date: 2016-05-11
SECOND MILITARY MEDICAL UNIV OF THE PEOPLES LIBERATION ARMY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Traditional physical introduction techniques include microinjection, electroporation, etc. Although the transfection efficiency is relatively high, it requires high technology and equipment, and can only be applied in limited tissues such as skin and muscle, and it is also effective for target cells. ~ Certain damage cannot be done inside the body
Although viral vectors (retroviral vectors, adenoviral vectors, and adenovirus-related viral vectors, etc.) have high transfection efficiency, they have obvious defects such as non-targeting and high immunogenicity, and the safety of viral vectors is problematic. has been controversial
However, this technical solution is to modify the temperature-sensitive polymer on the surface of the carrier, which will lead to the release of the drug that seals the carrier after the phase transition. In addition, the critical temperature should only be one temperature instead of a temperature range

Method used

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  • Temperature targeting-based nanogel gene delivery compound, and preparation method and application thereof
  • Temperature targeting-based nanogel gene delivery compound, and preparation method and application thereof
  • Temperature targeting-based nanogel gene delivery compound, and preparation method and application thereof

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Experimental program
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Effect test

Embodiment 1

[0044] Embodiment 1: the preparation of polycation PNIPAM / PEI nanogel

[0045] Add 0.80g 25KPEI (purchased from Sigma-Aldrich, USA) to 50mL PBS solution, adjust the pH to 7 with hydrochloric acid; accurately weigh 0.60g NIPAM crystals (purchased from (Shanghai) Chemical Industry Development Co., Ltd.), 14.00mg BIS crystals (purchased from (Shanghai) Chemical Industry Development Co., Ltd.) into the above solution:

[0046] Transfer the above mixed solution to a 250mL ground-necked flask (with a stirring bar inside), add

[0047] 50mL PBS solution;

[0048] Immerse the bottom of the flask into a constant temperature magnetic stirrer containing silicone oil, and heat the silicone oil to 50°C while stirring;

[0049] Introduce high-purity nitrogen (N 2 ) and stirred for 30min;

[0050] And add 250 μl 0.01M tert-butyl hydroperoxide (TBHP) to the system;

[0051] After 30 minutes, heat the silicone oil to 80°C, and continue to stir and react for 4 hours in a closed environment...

Embodiment 2

[0055] Embodiment 2: Polycation PNIPAM / PEI nanogel nuclear magnetic resonance characterization

[0056] Freeze-dry the gel after dialysis, take an appropriate amount of gel powder, dissolve in D 2 In O, we use NMR to analyze the components of the nanogel, such as figure 2 Shown, is the NMR of PEI, NIPAM, PNIPAM / PEI nanogel ( 1 H-NMR) spectrum. The absorption peaks are shown in the figure: (a) shows the characteristic proton resonance peak of the amino group (2.4ppm) of PEI, and (b) shows the characteristic proton resonance peak of NIPAM isopropyl group (0.85ppm) , PNIPAM / PEI nanogel has both the characteristic peaks of PEI and the characteristic peaks of PNIPAM. It can be seen that we have successfully grafted PEI and PNIPAM to form a nanogel copolymer.

Embodiment 3

[0057] Embodiment 3: the particle diameter of the complex solution of different N / P and zeta potential measurement

[0058] Preparation of samples to be tested: Dilute the dialyzed gel 10 times with Milli-Qwater;

[0059] Take 0.5mL of the sample to be tested, add it to the sample cell, and confirm that there are no bubbles in the measurement container. Each sample was measured 3 times. The measurement conditions are: 170 o Scattering angle, 25°C. Experimental results such as image 3 Shown: (A) is the particle size distribution diagram of polycation nanogel, from the figure it can be seen that its average particle diameter is 300nm ± 25nm; (B) is the zeta potential distribution diagram of polycation nanogel, its potential distribution 20mV±5mV.

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Abstract

The invention relates to the technical field of medicines, and discloses a temperature targeting-based nanogel plasmid compound used for delivering expression gene medicines, and a preparation method thereof. A temperature-sensitive core-shell structured nanogel is synthesized through a free radical coprecipitation technology, and the above carrier adopts temperature-sensitive polyisopropyl acrylamide (PNIPAM) as a core and positively charged polyethyleneimine (PEI) as a shell; and a targeting intelligent nanogel carrier material with high clinic application prospect is prepared through electrostatic adsorption and gene compounding by using high-temperature passive targeting in tumor microenvironment to realize good treatment of tumors by gene medicines. The compound makes a gene carrying administration system be well enriched in a tumor position to improve the gene transfection efficiency, and provides a new treatment mode for gene treatment of tumors.

Description

Technical field: [0001] The invention relates to the field of medical technology, in particular to a nanogel gene delivery compound based on temperature targeting and its preparation method and application. Background technique: [0002] Malignant tumors are one of the three major diseases that seriously threaten human health today. However, the three traditional treatment methods of surgical resection, chemotherapy, and radiotherapy have serious toxic side effects on normal organs and tissues of the body while treating tumors due to the lack of targeting. , and the late metastasis rate is high, the prognosis is poor, and its curative effect is difficult to further improve. In the field of targeted therapy for tumors, gene therapy research is receiving increasing attention and attention from scientists. tumor gene therapy y ) is a breakthrough in the research of tumor treatment. It is a treatment method developed with the maturity of gene manipulation and DNA recombination...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K48/00A61K9/51A61K47/48A61P35/00A61K47/58
Inventor 李威张莉孙赟陈迪柯长洪张付雷赵赫李华飞蒋成
Owner SECOND MILITARY MEDICAL UNIV OF THE PEOPLES LIBERATION ARMY
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