Mesoporous silica-lactobionic acid targeted nanoparticles loaded with Sorafenib/siRNA

A mesoporous silica, lacturonic acid target technology, applied in the direction of active ingredients of heterocyclic compounds, medical preparations of non-active ingredients, medical preparations containing active ingredients, etc., can solve the problem that the surface of tumor cells cannot be highly enriched problems such as low concentration, low biocompatibility, and lack of targeting molecules, to achieve the effect of improving anti-tumor effect, simple preparation method, and enhanced stability

Active Publication Date: 2017-11-17
FUZHOU UNIVERSITY
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0007] In 2012, Hartonno, S.B. et al. (ACS Nano, Volume 6, Page 2104, 2012) synthesized silicon oxide nanoparticles with large pore size (pore size greater than 10nm), and successfully modified positively charged polymers on the outer surface of the particles and in the pores The material is poly-L-lysine PLL (Poly-L-Lysine), and siRNA is adsorbed by electrostatic interaction to achieve siRNA interf

Method used

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  • Mesoporous silica-lactobionic acid targeted nanoparticles loaded with Sorafenib/siRNA
  • Mesoporous silica-lactobionic acid targeted nanoparticles loaded with Sorafenib/siRNA
  • Mesoporous silica-lactobionic acid targeted nanoparticles loaded with Sorafenib/siRNA

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Example Embodiment

[0033] Example 1 Synthesis of Mesoporous Silica Nanoparticles

[0034] Add 2 g of cetyltriethylammonium bromide, 0.1 g of triethanolamine and 20 mL of deionized water into the reaction flask, and react at 95°C for 1 h; Add 1.5 mL of ethyl ester, and continue to react at 95°C for 1 h after the addition; after the reaction, centrifuge at 12,000 rpm for 15 min at room temperature to obtain crude mesoporous silica nanomaterials, which are washed twice with deionized water and absolute ethanol , suspended the resulting solid in acidic ethanol (concentrated hydrochloric acid: absolute ethanol = 5:1, V:V), refluxed for 24 h to remove unreacted cetyltriethylammonium bromide, centrifuged, and deionized Washed with water and freeze-dried at -50 °C to obtain pure mesoporous silica nanoparticles.

[0035] figure 1 TEM image of the as-prepared mesoporous silica nanoparticles. It can be seen from the figure that the particle size is about 100 nm.

Example Embodiment

[0036] Example 2 Mesoporous silica nanoparticles (MSN-NH 2 ) preparation

[0037] Dissolve 100 mg of the mesoporous silica nanoparticles prepared in Example 1 in 20 mL of absolute ethanol, add 400 μg of 3-aminopropyltriethoxysilane, stir at room temperature for 12 h, centrifuge, and wash with ethanol several times to Remove unreacted 3-aminopropyltriethoxysilane, and freeze-dry to obtain surface amino-modified mesoporous silica nanoparticles (MSN-NH 2 ).

Example Embodiment

[0038] Example 3 Preparation of Sorafenib-loaded Mesoporous Silica Nanoparticles (SO@MSN)

[0039] Get 30 mg of MSN-NH prepared in Example 2 2 Dissolve in 30 mL of acetone, stir at room temperature for 1 h, add 20 mg of Sorafenib, stir for 30 min, then centrifuge at 13,000 rpm for 30 min, discard the supernatant, wash the precipitate with deionized water, freeze-dry, Sorafenib-loaded mesoporous silica nanoparticles (SO@MSN) were obtained.

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Abstract

The invention discloses mesoporous silica-lactobionic acid targeted nanoparticles loaded with Sorafenib/siRNA and an application of the mesoporous silica-lactobionic acid targeted nanoparticles loaded with the Sorafenib/siRNA in preparing of anticancer therapy drugs. The targeted nanoparticles are prepared through the steps that surface amination modifying is conducted on mesoporous silica nanoparticles; then inner pore channels of the mesoporous silica nanoparticles are internally loaded with the Sorafenib; and lactobionic acid is covalently coupled to the outer surfaces of the mesoporous silica nanoparticles, and the siRNA is adsorbed on the outer surfaces of the mesoporous silica nanoparticles through the electrostatic adsorption effect. According to the drug loading system, the stability of the siRNA can be improved, and targeted drug delivery of the Sorafenib can be further achieved, so that the toxic and side effects of the mesoporous silica-lactobionic acid targeted nanoparticles on normal cells are effectively relieved.

Description

technical field [0001] The invention belongs to the field of preparation of antitumor drugs, in particular to a mesoporous silicon dioxide-lacturonic acid targeting nanoparticle loaded with sorafenib / siRNA and an application thereof. Background technique [0002] In recent decades, the deterioration of the global environment has led to an increasing incidence of cancer, and the number of people dying from cancer is as high as 8.8 million every year. Currently, chemotherapy is still the main method of treating cancer. However, most of the chemotherapeutic drugs used in the treatment of cancer have the defects of lack of targeting, multi-drug resistance and low bioavailability, which largely limit their clinical use; research hotspots. [0003] Sorafenib is a multiple kinase inhibitor that can target multiple growth factor receptors, including VEGFR-1, VEGFR-2, VEGFR-3, PDGFR-b, c-KIT, FLT-3 and RET, etc. Its structural formula is: . Sorafenib was approved by the FDA in ...

Claims

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Application Information

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IPC IPC(8): A61K48/00A61K31/713A61K31/44A61K47/52A61K47/26A61K47/04A61K9/51A61P35/00
CPCA61K9/5115A61K9/5123A61K31/44A61K31/713A61K47/26A61K2300/00
Inventor 邵敬伟张颖郑桂容
Owner FUZHOU UNIVERSITY
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