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Compound containing cell targeting antibodies and Poly(I:C), preparation method and applications thereof

A cell-targeting and compound technology, applied in the field of medicine, can solve the problems of not being able to use human beings, importing, etc., and achieve the effect of enhancing the production of interferon and pro-inflammatory factors

Active Publication Date: 2018-02-16
XIEHE HOSPITAL ATTACHED TO TONGJI MEDICAL COLLEGE HUAZHONG SCI & TECH UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In the mouse model, TLR3 in the liver can be activated by high-pressure water injection, but this method cannot be used in humans, and it is currently unable to effectively import poly(I:C) into the liver of patients

Method used

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  • Compound containing cell targeting antibodies and Poly(I:C), preparation method and applications thereof
  • Compound containing cell targeting antibodies and Poly(I:C), preparation method and applications thereof
  • Compound containing cell targeting antibodies and Poly(I:C), preparation method and applications thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0051] This embodiment provides a compound CaP / PEI / poly(I:C) / SiO comprising a cell targeting antibody and Poly(I:C) 2 -S-Ab, wherein, Ab is the targeting antibody CD146 or IgG1, the compound includes calcium phosphate nanoparticles as the core, the surface of the core is grafted with PEI, the surface of the core is adsorbed and loaded with Poly(I:C), and the outside of the core is A silica shell linked to antibody CD146 or IgG1 via cyclohexane-1-carboxylate-3-sulfosuccinimidyl ester.

[0052] The above compound CaP / PEI / poly(I:C) / SiO containing intrahepatic cell targeting antibody and Poly(I:C) 2 -S-Ab, ie CaP / PEI / poly(I:C) / SiO 2 -S-CD146 and CaP / PEI / poly(I:C) / SiO 2 -The preparation method of S-IgG1 comprises the following steps:

[0053] The nanoparticles were prepared using the following chemicals: branched polyethylene (PEI), calcium lactate, diammonium phosphate, tetraethoxysilane (TEOS), trimethoxysilane (MPS), triethoxysilane (APTES), cyclohexane-1-carboxylic acid-3-s...

Embodiment 2

[0065] This embodiment provides a compound CaP / PEI / poly(I:C) / SiO comprising a cell targeting antibody and Poly(I:C) 2 -S-Ab, wherein, Ab is the targeting antibody F4 / 80 or IgG2, the compound includes calcium phosphate nanoparticles as the core, the surface of the core is grafted with PEI, the surface of the core is adsorbed and loaded with Poly(I:C), and the core is The exterior is a silica shell to which antibody F4 / 80 or IgG2 is attached via cyclohexane-1-carboxylate-3-sulfosuccinimide ester.

[0066] The above compound CaP / PEI / poly(I:C) / SiO containing cell-targeting antibody and Poly(I:C) 2 -S-Ab, ie CaP / PEI / poly(I:C) / SiO 2 -S-F4 / 80 and CaP / PEI / poly(I:C) / SiO 2 -The preparation method of S-IgG2 is basically the same as that of Example 1, the difference is:

[0067] Step 5: Nanoparticles are covalently bound to different antibodies (CaP / PEI / poly(I:C) / SiO 2 -S-Ab)

[0068] 150 μL of antibody (anti-mouse F4 / 80 or anti-mouse IgG2) was mixed with 40 μL of cyclohexane-1-carbo...

Embodiment 3

[0070] This embodiment provides a compound CaP / PEI / poly(I:C) / SiO comprising a cell targeting antibody and Poly(I:C) 2 -S-Ab, wherein, Ab is targeting antibody CD146, F4 / 80, IgG1 or IgG2, and described compound comprises calcium phosphate nano-particle as inner core, and inner core surface is grafted with PEI, and inner core surface is adsorbed and loaded with Poly(I: C), the outside of the inner core is a silica shell, and the silica shell is linked to antibody CD146, F4 / 80, IgG1 or IgG2 through cyclohexane-1-carboxylate-3-sulfosuccinimide ester.

[0071] The above compound CaP / PEI / poly(I:C) / SiO containing cell-targeting antibody and Poly(I:C) 2 -S-Ab, ie CaP / PEI / poly(I:C) / SiO 2 -S-CD146, CaP / PEI / poly(I:C) / SiO 2 -S-F4 / 80, CaP / PEI / poly(I:C) / SiO 2 -S-IgG1 and CaP / PEI / poly(I:C) / SiO 2 -The preparation method of S-IgG2 is basically the same as that of Example 1, the difference is:

[0072] Step 2: Synthesis of poly(I:C)-loaded CaP / PEI (CaP / PEI / poly(I:C))

[0073] 1 mL of CaP / ...

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Abstract

The present invention provides a compound CaP / PEI / poly(I:C) / SiO2-S-Ab containing cell targeting antibodies and Poly(I:C), wherein the compound uses calcium phosphate nanoparticles as the core, the surface of the core is grafted with PEI, the Poly(I:C) is adsorbed and loaded on the surface of the core, the outer portion of the core is a silica shell, and the silica shell is linked to four differentcell targeting antibodies (such as CD146 antibody targeting liver sinusoidal endothelial cells, F4 / 80 antibody targeting kupffer cells, IgG1 isotype control antibody targeting IgG1 antibody expression Fc receptor cells, and IgG2 isotype control antibody targeting IgG2 antibody expression Fc receptor cells). The invention further provides a preparation method and medical uses of the compound. According to the present invention, with the compound, the poly(I:C) can reach the intrahepatic cells in the targeted manner so as to bind the poly(I:C) to TLR3, such that the generation of interferons and proinflammatory cytokines can be enhanced by activating different immune cell TLR3-mediated signaling pathways so as to provide the anti-HBV virus effect.

Description

technical field [0001] The present invention relates to the field of medical technology, in particular to a compound CaP / PEI / poly(I:C) / SiO containing cell targeting antibody and Poly(I:C) 2 -S-Ab and its preparation method and application. Background technique [0002] Among various nanoparticles, calcium phosphate nanoparticles have the characteristics of high biocompatibility, high biodegradability, small size and high affinity, and can be covalently functionalized with some nucleic acids, because of their considerable application prospects. The nanoparticles have been used in various fields, such as transfection, gene silencing, drug delivery, photodynamic therapy, etc. Some macromolecules are often unable to penetrate the cell membrane, therefore, an effective carrier such as nanoparticles is required. [0003] Calcium phosphate nanoparticles, about 100 nm in size, are easily taken up by cells and subsequently dissolved in lysosomes. Multiple studies have demonstrated...

Claims

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Application Information

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IPC IPC(8): A61K39/395A61K47/58A61K47/69A61K9/51A61K31/713A61P31/12A61P29/00A61P35/00
CPCA61K9/0019A61K9/5138A61K31/713A61K39/395A61K2300/00
Inventor 吴珺邹诗黄顺梅杜艳芹马赛厄斯·埃普尔维多利亚·索科洛娃
Owner XIEHE HOSPITAL ATTACHED TO TONGJI MEDICAL COLLEGE HUAZHONG SCI & TECH UNIV
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