Cell-nucleus-targeted antitumor nanomedicine carrier and preparation method and application thereof

A nano-drug carrier and cell nucleus technology, applied in the fields of polymer chemistry and biomedical engineering, to prolong the circulation time of body fluids, promote enrichment, and realize the effects of release

Active Publication Date: 2017-12-22
SUN YAT SEN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, due to a large number of obstacles, it is difficult for free anticancer drugs and DNA to remain active when they reach the nucleus

Method used

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  • Cell-nucleus-targeted antitumor nanomedicine carrier and preparation method and application thereof
  • Cell-nucleus-targeted antitumor nanomedicine carrier and preparation method and application thereof
  • Cell-nucleus-targeted antitumor nanomedicine carrier and preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0041] Example 1 Synthesis of polymer micelles NLS-PEG-PAsp (BzA) and mPEG-PAsp (DBA-DMMA)

[0042] (1) Synthesis of benzyloxycarbonyl aspartic anhydride (BLA-NCA)

[0043]

[0044] Synthesize β-aspartic acid benzyl ester first, and the steps are as follows: add 100 ml of anhydrous diethyl ether into a 500 ml single-mouthed eggplant-type bottle, slowly add 10 ml of concentrated sulfuric acid under stirring, and add 100 ml after the liquid in the bottle returns to room temperature Benzyl alcohol was concentrated by rotary evaporation to remove ether, and 13.3 g of aspartic acid was added to a one-necked bottle, and the reaction was stirred at room temperature for 24 h. After the reaction is complete, add 300 ml of 95% ethanol to the single-necked bottle and shake to mix evenly, and slowly add concentrated NH 3 •H 2 O, gradually produce white precipitate, stop adding concentrated NH when the pH value is adjusted to about 7 3 •H 2 O, the cloudy solution was placed in a refri...

Embodiment 2

[0066] Example 2 Preparation of drug-loaded micelles (NLS-PEG-PAsp(BzA)@DOX)

[0067] Take 20 mg NLS-PEG-PAsp (BzA) dissolved in 3 ml DMSO, another 2.5 mg DOX·HCl dissolved in 1 ml DMSO, and add 60 μl TEA and stir for 2 h. The two were mixed together and slowly dropped into 30 ml of ultrapure water while ultrasonicating, and dialyzed against water for 12 h after completion.

Embodiment 3

[0068] Example 3 Drug Release of NLS-PEG-PAsp(BzA)@DOX

[0069]The conventional dialysis method was used to test the in vitro release experiment to simulate the release of the drug loaded in the micelles. The DOX-loaded polymer micelle solution was divided into three parts on average, and the conditions of the three samples were set at pH 7.4, pH 6.5, and pH 5.0, respectively. The release experiment was carried out in a constant temperature water bath culture shaker at 37 °C. In addition, three parallel groups were set up for each sample. In each group, 2 ml of micellar solution was added to a 14 kDa dialysis bag, and 10 ml of PBS buffer under the same conditions were added to the outside of the dialysis bag for simulated release in a shaker. Then at different set time points (1 h, 2 h, 4 h, 6 h, 8 h, 10 h, 12 h, 24 h), the solutions outside the dialysis bags of each group were collected, and the same volume of PBS was added respectively buffer. The absorbance at 480.25 nm o...

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Abstract

The present invention relates to a cell-nucleus-targeted antitumor nanomedicine carrier and a preparation method and application thereof. The cell-nucleus-targeted antitumor nanomedicine carrier comprises polymer micelle NLS-PEG-PAsp (BzA) and a pH-sensitive negatively-charged polymer constructed on the surface of the polymer micelle by electrostatic interaction, the pH-sensitive negatively-charged polymer can changed into positively-charged from negatively-charged when pH is 6.5 to 6.8, the size of the polymer micelle is 20nm-40nm, and the particle size of the nanomedicine carrier is 100nm-110nm. The cell-nucleus-targeted antitumor nanomedicine carrier can stably circulate in body and is effectively enriched in a tumor site through EPR effect. When a nano medicine reaches tumor microenvironment, under the condition of the pH of 6.5-6.8, a negative polymer protective layer compounded on the surface of the polymer micelle is changed into positively-charged from negatively-charged, and further is removed from the surface of nanoparticles of the polymer micelle, the positively-charged polymer micelle facilitates endocytosis, and finally the positively-charged polymer micelle targets tumor nuclei under the action of nuclear localization signal peptide to release the antitumor medicine in the nucleus.

Description

technical field [0001] The invention belongs to the field of polymer chemistry and biomedical engineering, and more specifically relates to a nucleus-targeted anti-tumor nano drug carrier and a preparation method thereof. Background technique [0002] Targeted nano-drug delivery system can not only reduce toxic side effects, but also enhance therapeutic effect, which has received great attention in recent years. Currently, nanoparticles such as metals, oxides, semiconductors, polymers, and magnetic nanoparticles are widely used to target tumor cells. However, most studies only focus on the distribution of nanoparticles in the cell, mainly in the cytoplasm, but little attention is paid to the nucleus. In fact, the nucleus is the ultimate target. It is the heart of the cell, where genetic information is replicated and transcribed, and where most therapeutic drugs act. Nucleus-targeted drug delivery systems can kill cancer cells more effectively and directly. [0003] The nu...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/69A61K31/704A61K47/60A61P35/00A61K9/107A61K47/42
CPCA61K9/1075A61K31/704A61K47/42
Inventor 帅心涛万文清韩世松黄金生
Owner SUN YAT SEN UNIV
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