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Mesoporous ruthenium nanoparticles for targeted therapy of colorectal cancer as well as preparation method and application of mesoporous ruthenium nanoparticles

A nanoparticle and targeted therapy technology, applied in the field of mesoporous ruthenium nanoparticles and its preparation, can solve problems such as the discovery of hollow mesoporous metal ruthenium nanoparticles

Active Publication Date: 2019-04-09
JINAN UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] So far, there is no report on the synthesis of uniform hollow mesoporous metal ruthenium nanoparticles, which can be functionalized for combined photothermal and immune therapy of colorectal cancer

Method used

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  • Mesoporous ruthenium nanoparticles for targeted therapy of colorectal cancer as well as preparation method and application of mesoporous ruthenium nanoparticles
  • Mesoporous ruthenium nanoparticles for targeted therapy of colorectal cancer as well as preparation method and application of mesoporous ruthenium nanoparticles
  • Mesoporous ruthenium nanoparticles for targeted therapy of colorectal cancer as well as preparation method and application of mesoporous ruthenium nanoparticles

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0079] Embodiment 1: Preparation of hollow mesoporous ruthenium nanoparticles

[0080] (1) Measure 173 μL of perchloric acid (HClO 4 ), dilute to 10mL with distilled water to prepare a 0.2mol / L perchloric acid storage solution; meanwhile weigh 37.83mg of sodium borohydride (NaBH 4 ), and distilled water to 10 mL to prepare a 0.1 mol / L sodium borohydride stock solution.

[0081] (2) Preparation of amino-modified colloidal silica particles: 19.65 mL of absolute ethanol, 0.61 mL of water, and 1.7 mL of ammonia water (aqueous solution containing 25% to 28% of ammonia) were magnetically stirred for about 20 minutes to form a uniform solution, and then slowly Add dropwise a mixed solution of 1.34mL tetraethyl orthosilicate and 6.7mL absolute ethanol, after the dropwise addition, seal the bottle mouth with polyvinyl chloride film, react for 10h, wash with absolute ethanol for 3 times and centrifuge to obtain Monodisperse silica particles with a particle size of 100nm. Add 0.5006g ...

Embodiment 2

[0085] Example 2: Preparation of functionalized nanocomposites

[0086] (1) Weigh 11 mg of ruthenium complex (RBT, [Ru(bpy) 2 (tip)] 2+ ), with PBS buffer solution to 10mL to prepare the ruthenium complex storage solution; wherein, the ruthenium complexes with fluorescent properties refer to the following documents (Wang C, Yu Q, Yang L, et al.Ruthenium(II) polypyridyl complexes stabilize the bcl-2promoter quadruplex and induce apoptosis of Hela tumor cells[J].Biometals,2013,26(3):387-402.) obtained. Weigh 25 mg of hollow mesoporous ruthenium nanoparticles (prepared in Example 1), and dilute to 10 mL with PBS buffer to prepare a ruthenium nanoparticle storage solution.

[0087] (2) Loading of ruthenium complexes and modification of PEG: Take 2mL of 2.5mg / mL ruthenium nanoparticle storage solution, add it to 1mL of 1.1mg / mL ruthenium complex storage solution, and then sonicate the mixture at 50Hz for 1h After uniform dispersion, stir magnetically at a constant speed of 400rp...

Embodiment 3

[0089] Embodiment 3: Photothermal effect evaluation of nanometer ruthenium, nanocomposite

[0090] Get the hollow mesoporous ruthenium nanoparticles prepared in Example 1 (configured into a 5 μg / mL solution) and the functionalized nanocomposite prepared in Example 2 (configure 1, 5, 10, 20 μg / mL solution), in 300mW cm -2 808nm near-infrared light (NIR) was irradiated for 5 minutes to detect its photothermal effect, and PBS buffer was used as a negative control. During the near-infrared light irradiation process, the temperature of the solution was measured by a thermometer every 1 minute to monitor its temperature change, and an intuitive thermal image was taken by a FLIR E8 infrared thermal imager. like image 3 As shown, it can be observed that both the hollow mesoporous ruthenium nanoparticles and the functionalized nanocomposite exhibit excellent photothermal effects, and the temperature can be rapidly increased to 50 °C. In addition, the hollow mesoporous ruthenium nan...

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Abstract

The invention discloses mesoporous ruthenium nanoparticles for targeted therapy of the colorectal cancer as well as a preparation method and application of the mesoporous ruthenium nanoparticles. Thepreparation method comprises the following steps: (1), dissolving ruthenium trichloride in a perchloric acid solution, then adding a nonionic surfactant, and mixing uniformly to obtain a mixed solution I; (2), adding amino-modified colloidal silicon dioxide nanoparticles into the mixed solution I, and ultrasonically mixing to obtain a uniform mixed solution II; (3), adding a sodium borohydride solution into the mixed solution II, performing an ultrasonic reaction, and after completion of the reaction, washing by using water and centrifuging to obtain an intermediate product; (4), dispersing the intermediate product in a hydrofluoric acid solution, then washing by using water and drying to obtain the mesoporous ruthenium nanoparticles for the targeted therapy of the colorectal cancer. The ruthenium nanoparticles prepared according to the preparation method provided by the invention have large specific surface area, can be loaded with a ruthenium complex and a coupled bispecific antibodyand are applied to targeted resistance to the colorectal cancer in combination with photothermal and immunotherapy.

Description

technical field [0001] The invention belongs to the technical field of nano-medicines, and in particular relates to a mesoporous ruthenium nanoparticle for targeted therapy of colorectal cancer, a preparation method and application thereof. Background technique [0002] Colorectal cancer (CRC) is the third most common malignancy and the fourth leading cause of cancer death in the world, with approximately 1.4 million new cases and nearly 700,000 deaths in 2012. The incidence distribution of CRC varies widely, with more than two-thirds of cases and about 60% of deaths occurring in countries with a high or very high Human Development Index (HDI). Now, many countries with medium and high HDI, especially Eastern Europe, Asia, and South America, have found a rapid increase in CRC incidence and mortality, and the incidence rate in countries with very high HDI is as high as 6 times that in countries with low HDI. Given temporal characteristics and demographic projections, the glob...

Claims

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Application Information

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IPC IPC(8): A61K41/00A61K47/68A61K47/60A61K47/69A61K49/00A61P35/00
CPCA61K41/0052A61K49/0019A61K49/0054A61K49/0058A61K49/0093A61K47/60A61K47/6801A61K47/6863A61K47/6949A61P35/00
Inventor 徐萌刘亚楠陈旭朱旭峰刘杰
Owner JINAN UNIVERSITY
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