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Dual-targeting ursolic acid (UA)/siRNA loaded fluorescent mesoporous silica dioxide-hyaluronic acid and application

A technology of mesoporous silica and hyaluronic acid, which is applied in the field of biological nanomaterials, can solve the problems of limiting the scope of application, failing to take advantage of the characteristics of mesoporous materials, and not co-loading drugs and siRNA in combination with drugs, etc., to achieve improved Anticancer effect, enhanced antitumor effect, enhanced bioavailability

Active Publication Date: 2016-02-24
FUZHOU UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] Patent CN104027821A discloses a nanoparticle loaded with siRNA and its application, by inducing siRNA to be loaded into the inner channel of mesoporous silica, but this method only realizes the loading of siRNA, and does not combine drugs with siRNA Co-loading into the inner channels of mesoporous silica for drug combination
In 2009, Small magazine reported that A.M.Chen et al. physically entrapped the drug doxorubicin into the inner pores on the surface of mesoporous silica, then modified G2PAMAM on the outer surface of MSN, and then used electrostatic adsorption to adsorb siRNA to PAMAM, thereby achieving co-delivery of drugs and siRNA (ChenAM, ZhangM, WeiD, et al. Co‐deliveryofDoxorubicinandBcl‐2siRNAbyMesoporousSilicaNanoparticlesEnhancestheEfficacyofChemotherapyinMultidrug‐ResistantCancerCells[J].Small,2009,5(23):2673-2677.), but this method is only modified The adsorption of siRNA on the outer surface of mesoporous silica fails to take advantage of the characteristics of the pore structure and large pore volume of mesoporous materials, and the siRNA adsorbed on the surface of nanomaterials is easily degraded by nucleases in vivo, thus limiting its performance. scope of application

Method used

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  • Dual-targeting ursolic acid (UA)/siRNA loaded fluorescent mesoporous silica dioxide-hyaluronic acid and application
  • Dual-targeting ursolic acid (UA)/siRNA loaded fluorescent mesoporous silica dioxide-hyaluronic acid and application
  • Dual-targeting ursolic acid (UA)/siRNA loaded fluorescent mesoporous silica dioxide-hyaluronic acid and application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0030] Example 1 Surface Amination Modified Fluorescently Labeled Mesoporous Silica (FMSN-NH 2 ) preparation

[0031] (1) Weigh 5 mg FITC and dissolve in 3 mL ethanol, then add 20 μL 3-aminopropyltriethoxysilane, and stir for 24 hours in the dark.

[0032] (2) Mix 0.05gCTAB, 0.16mLNH 3 .H 2 O and 24 mL of ultrapure water were mixed and dissolved, and stirred at room temperature for 1 hour. 0.15 mL LTEOS was added and stirring was continued for 1 hour at room temperature. Add the ethanol solution of APTES-FITC prepared in the above step (1), and at the same time add 0.075mLTEOS, and continue stirring at room temperature for 4 hours. Centrifuge at 12000rpm for 20min, wash with water and ethanol for several times, then disperse it into the acid solution of ethanol (ethanol: hydrochloric acid = 10:1, V:V) and reflux for 24 hours to remove the unreacted raw material CTAB, centrifuge again, Wash with water and ethanol, and freeze-dry to obtain fluorescently labeled mesoporous s...

Embodiment 2

[0034] Example 2 Surface Amination Modified Fluorescently Labeled Mesoporous Silica (FMSN-NH 2 ) preparation

[0035] As in Example 1, only the amount of ammonia water in step (2) was changed to 0.23mL (256mM), and other conditions were not changed, and the fluorescently labeled mesoporous silica (FMSN-NH 2 ), and its particle size is 160nm.

Embodiment 3

[0036] Example 3 Preparation of fluorescent mesoporous silica nanoparticles loaded with ursolic acid (UAFMSN)

[0037] Weigh 30 mg of the fluorescently labeled mesoporous silica prepared in step (2) of Example 1 and disperse into 30 mL of methanol, ultrasonically disperse and dissolve for 1 hour, add 20 mg of UA, stir at room temperature for 24 hours, centrifuge (keep the supernatant), water Wash with ethanol and centrifuge separately, freeze-dry to obtain ursolic acid-loaded fluorescent mesoporous silica nanoparticles (UAFMSN).

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Abstract

The invention relates to dual-targeting ursolic acid (UA) / siRNA loaded fluorescent mesoporous silica dioxide-hyaluronic acid and application. The technical scheme of the invention lies in that 1, fluorescently-labeled mesoporous silica dioxide nano particles are synthesized through the template method; 2, the surface of FMSN is subjected to amino modification through 3-aminopropyltriethoxysilane; 3, ursolic acid (UA) and siRNA are jointly loaded into porous channels of the nano particles; 4, hyaluronic acid is loaded into the outer surfaces of the nano material in a wrapping manner through electrostatic absorption, so as to obtain the dual-targeting ursolic acid (UA) / siRNA loaded fluorescent mesoporous silica dioxide-hyaluronic acid nano particles. According to the dual-targeting ursolic acid (UA) / siRNA loaded fluorescent mesoporous silica dioxide-hyaluronic acid and application, the prepared nano material is uniform in particle size distribution, and good in dispersibility, the stability of siRNA can be improved, and besides, siRNA can further specifically target tumor cell surface adhesion molecules like ICAM and CD44, therefore the anti-tumor effect of drugs can be greatly improved, and the toxic and side effect of the drugs can be further reduced.

Description

technical field [0001] The invention relates to the field of biological nanomaterials, in particular to a dual-targeted fluorescent mesoporous silica-hyaluronic acid nanoparticle loaded with ursolic acid / siRNA and its application. Background technique [0002] Combining genes and anti-tumor drugs for targeted delivery can simulate the combination drug mode in clinical tumor treatment, and synergize in different ways to improve their respective anti-tumor effects and reduce the toxic and side effects of drugs on normal tissues and cells. [0003] RNA interference (RNA interference, RNAi) refers to the processing of double-stranded RNA (double-stranded RNA, dsRNA) into a 21-25 nucleotide small molecule RNA (siRNA) through the specific endonuclease Dicer. The mRNA coding region or UTR region is completely paired, degrades the target mRNA, and causes post-transcriptional silencing of the gene. Although siRNA has great application value in gene therapy, it is unstable in organis...

Claims

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Application Information

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IPC IPC(8): A61K48/00A61K47/04A61K31/7105A61K31/56A61P35/00
Inventor 邵敬伟迟婷
Owner FUZHOU UNIV
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