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Trastuzumab bond-linking gold nanorod compound, preparation method and application thereof in diagnosis and treatment of HER2 positive breast cancer

A technology of trastuzumab and gold nanorods, applied in the field of biomedicine, can solve problems such as inability to reach the exact lesion site, insufficient penetration, and single radial adjustment range

Active Publication Date: 2016-05-25
HARBIN MEDICAL UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, tumor hyperthermia is a complex process. Because different wavelengths of light have different penetration capabilities on tissues, the thermal efficiency of light with enhanced tissue penetration will decrease, and if the penetration is insufficient, it will not be able to reach the exact lesion.
Since the commonly used gold nanoshells have a single radial adjustment range (only the radius of the ball is adjustable), they cannot meet the needs of treating tumors of different sizes and depths in the body. We bonded gold nanorods to trastuzumab, and simultaneously Combined with trastuzumab, gold nanorods are linked by cysteine-porphyrin bonds, and porphyrin near-infrared fluorescence imaging is used to identify tumor lesions, achieving the effect of image localization and targeted hyperthermia

Method used

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  • Trastuzumab bond-linking gold nanorod compound, preparation method and application thereof in diagnosis and treatment of HER2 positive breast cancer
  • Trastuzumab bond-linking gold nanorod compound, preparation method and application thereof in diagnosis and treatment of HER2 positive breast cancer
  • Trastuzumab bond-linking gold nanorod compound, preparation method and application thereof in diagnosis and treatment of HER2 positive breast cancer

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Experimental program
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Effect test

Embodiment 1

[0032]Example 1 Preparation of trastuzumab-linked gold nanorod complex

[0033] Embodiments and steps of the present invention:

[0034] 1) Preparation of gold nanorods

[0035] a. Preparation of gold seed solution: Add 7.5ml of 0.1M CTAB solution to a 50ml beaker, add 250μl of 0.01M chloroauric acid solution under slight stirring, and then add freshly prepared 0.01M boron at 0°C 60 μl of sodium hydride solution, stirred gently at a temperature of about 25°C for 2 minutes, and set aside.

[0036] b. Preparation of growth solution: Take several 50ml beakers, and add the following solutions in turn to the beakers: 10ml of 0.1M CTAB solution, 425μl of 0.01M chloroauric acid solution, 60μl, 80μl or 100μl of 0.01M silver nitrate solution ( Different amounts of silver nitrate can generate gold nanorods with different aspect ratios), and 67 μl of 0.1M ascorbic acid solution to obtain a growth solution;

[0037] c. Preparation of gold nanorods: Add 105 μl of gold seed solution into...

Embodiment 2

[0044] Example 2 Application of trastuzumab-linked gold nanorod complex in diagnosis and treatment of HER2-positive breast cancer

[0045] 1. The HER2 highly expressed BT474 breast cancer cell line was cultured in a six-well plate, and 100ug / ml of the trastuzumab-linked gold nanorod complexes linked to different amounts of cysteine ​​prepared in Example 1 were added to each well (The addition of silver nitrate solution is 80 μl), 37 ℃ 5% CO 2 After incubation for 24 hours, the binding of gold nanorod complexes to receptors on the surface of breast cancer cells and fluorescence imaging were observed through a fluorescence microscope. The results were as follows: figure 2 As shown, it can be seen that as the proportion of cysteine ​​increases (0.75g, 1g and 1.25g from left to right), the porphyrin red fluorescence is stronger (arrow), and the cells bind more trastuzumab , better drug targeting.

[0046] 2. Apply 96-well plates to culture BT474 breast cancer cells, add PBS sol...

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Abstract

The invention discloses a trastuzumab bond-linking gold nanorod compound, a preparation method and application thereof in the diagnosis and treatment of HER2 positive breast cancer, which overcome the defects of poor regulation of photo-thermal conversion efficiency and incapability of location of targeting gold nanoparticles. The preparation method comprises the following steps: firstly, preparing a gold nanorod with a certain length-diameter ratio, wherein the longitudinal absorption peak is 650 to 850nm, and the nanorod is capable of meeting the optimal optical wavelength penetrating through tissue of a human body; then connecting cysteine with porphyrinfluorescent molecules, next, through the action of an Au-S bond, bond-linking the gold nanorod with a cysteine-porphyrin compound, finally through a glutaraldehyde chemical crosslinking method, bond-linking a gold nanorod-cysteine-porphyrin compound with a drug trastuzumab. The obtained trastuzumab bond-linking gold nanorod compound is capable of showing in-situ or micro metastatic focus, and performing a targeting photo-thermal therapy on a detected tumor focus, so that the difficult problem of drug resistance of tumor can be effectively solved.

Description

technical field [0001] The invention relates to a trastuzumab-linked gold nanorod complex, and also relates to a preparation method of the nanorod complex and its application in the diagnosis and treatment of HER-2 positive breast cancer. The invention belongs to the technical field of biomedicine. Background technique [0002] With the clinical development and application of new drugs and new methods, the treatment effect of early breast cancer has been greatly improved, but the 5-year survival rate of stage III and stage IV breast cancer is still only 57% and 20%, among which epidermal growth factor 2 receptor (HER2)-positive breast cancer patients have a high risk of recurrence and metastasis, and the prognosis is particularly poor. In 2006, the Swiss company Roche developed the first molecularly targeted drug against the HER2 target of breast cancer cells—trastuzumab, which can bind to HER2, block HER2-related tumor growth signaling pathways, and inhibit HER2 excess. Pr...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K41/00A61K47/48A61K49/00A61K33/24A61P35/00
CPCA61K33/24A61K41/0052A61K49/0036
Inventor 张清媛康欣梅
Owner HARBIN MEDICAL UNIVERSITY
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