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A kind of integrated nanoparticle for diagnosis and treatment of breast cancer and its preparation method

A nanoparticle, breast cancer technology, applied in preparations for in vivo experiments, wave energy or particle radiation treatment materials, pharmaceutical formulations, etc. Lack of targeting and other problems, to achieve the effect of large molar absorption coefficient

Active Publication Date: 2018-12-21
NANJING UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the hysteresis of one of the cores of this technology—the integrated reagents for diagnosis and treatment—severely limits its development.
Mainly attributed to: (1) The reagents for the integration of diagnosis and treatment lack specific targeting; (2) The reagents for the integration of diagnosis and treatment are mostly simply assembled from existing diagnostic reagents and therapeutic drugs, and lack synergy in function; (3) ) The integration of diagnosis and treatment reagents is difficult to accurately and non-destructively monitor the therapeutic effect of cancer in real time

Method used

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  • A kind of integrated nanoparticle for diagnosis and treatment of breast cancer and its preparation method
  • A kind of integrated nanoparticle for diagnosis and treatment of breast cancer and its preparation method
  • A kind of integrated nanoparticle for diagnosis and treatment of breast cancer and its preparation method

Examples

Experimental program
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Effect test

Embodiment 1

[0025] Example 1: In vitro screening of MDA-MB-231 breast cancer cell-specific nucleic acid aptamers:

[0026] Using CELL-SELEX technology, the breast cancer cell MDA-MB-231 was used as the target cell, and the normal breast epithelial cell MCF-10A was used as the anti-screening cell. After 15 rounds of screening, the nucleic acid aptamer of the breast cancer cell was obtained, and the nucleic acid was sequenced. Synthesis of aptamers.

Embodiment 2

[0027] Example 2: Combining figure 2 , synthesis of acidic pH-triggered fluorescent probe BDP-688

[0028] 1) Synthesis of compound I: 100 mg of 2-(thiophene-2-yl)-4H-thiophene[3,2-b]pyrrole (compound a) was dissolved in 50 mL of dichloromethane under the protection of argon, and stirred to dissolve in the dark. Add 41 mg m-nitro-p-hydroxybenzaldehyde and 1 drop of trifluoroacetic acid (TFA) to solution a, and stir at room temperature for 12 hours. Add 55 mg of 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ), continue stirring for 1 hour, then add 3 mL of triethylamine (TEA) and 3 mL of boron trifluoride diethyl ether (BF 3 ·Et 2 O), stirred for 3 hours. Add an appropriate amount of distilled water to quench the reaction, filter, collect the filtrate, extract with chloroform, wash with distilled water, and wash the organic layer with anhydrous Na 2 SO 4 After drying, the organic solvent was distilled off under reduced pressure and separated by column chromatography to ob...

Embodiment 3

[0030] Example 3: Binding image 3 , synthesis of near-infrared light-activated photosensitizer R16FP

[0031] 217 mg of phenanthrene[9,10-c]pyrrole was dissolved in 350 mL of dry dichloromethane under the protection of argon, and stirred to dissolve. The reaction system was protected from light and cooled to -50°C, 346 mg of 4-hexadecyloxybenzaldehyde was added, and stirred overnight. Add 40mL boron trifluoride diethyl ether (BF 3 ·Et 2 (0), stirred and reacted for 2 hours, then the reaction system returned to room temperature, and continued to stir for 48 hours. Add 227 mg DDQ and 3 drops of triethylamine (TEA) to the solution, stir the reaction for 1 hour, remove the organic solvent under reduced pressure, and separate by column chromatography to obtain a dark red solid. Recrystallization from chloroform / methanol solution gave the dark red product R16FP with a yield of 13%. 1 H-NMR (500MHz, CD 2 C1 2 ) Analysis results: δ8.43(d, J=8.1Hz, 4H), 7.74-7.59(m, 8H), 7.35-7...

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Abstract

The invention relates to a nanoparticle (Apt-TNP) for integration of breast cancer diagnosis and treatment and a preparation method thereof. The Apt-TNP utilizes polylactic acid-polyethylene glycol as a carrier, the interior of the Apt-TNP is embedded with a pH-responsive fluorescent probe BDP-688 and a near-infrared photosensitizer R16FP, and the surface of the Apt-TNP is covalently coupled with a breast cancer-specific aptamer. The Apt-TNP can specifically bond with breast cancer cells and reach to lysosome, the lysosome triggers the BDP-688 in an acidic pH environment so that fluorescence is produced and accurate imaging of cancer cells is realized. The R16FP is activated by laser having wavelength of 808nm and produces active oxygen, and release of cathepsin in lysosome is initiated so that cancer cell apoptosis is realized and photodynamic therapy is realized. Cell apoptosis develops along with pH change so that BDP-688 fluorescence is reduced and real-time monitoring of curative effects is realized. The Apt-TNP has functions of breast cancer targeting imaging, high-efficiency treatment and curative effect monitoring and has a good clinical application potential.

Description

1. Technical field [0001] The invention relates to an integrated nanoparticle for diagnosis and treatment of breast cancer and a preparation method thereof. 2. Background technology [0002] Traditional cancer diagnosis and treatment are two independent processes with a long time interval, which easily delays the best time for treatment, leads to poor curative effect or over-treatment, and increases the pain and risk of patients. In order to solve this problem, the integrated diagnosis and treatment technology developed by combining the two processes of diagnosis and treatment has attracted widespread attention. This technology can provide real-time feedback on the curative effect, improve the efficiency of diagnosis and treatment, and reduce the toxic and side effects of drugs. However, the hysteresis of one of the cores of this technology—the integrated reagents for diagnosis and treatment—severely limits its development. Mainly attributed to: (1) The reagents for the in...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K49/00A61K41/00A61K47/34A61K47/26A61K9/16A61P35/00
Inventor 鞠熀先田蒋为丁霖于俊生沈珍
Owner NANJING UNIV
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