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A permeation-enhanced gold nanocluster drug-loaded targeting agent and its preparation method and application

A gold nanocluster, penetration enhancement technology, applied in nanotechnology, nanotechnology, nanotechnology for materials and surface science, etc., can solve problems such as limited prospects, difficult metabolism, and high toxicity of gold nanorods, and achieve improved safety. improve tissue permeability, enhance the effect of penetration

Active Publication Date: 2021-12-28
CHINA PHARM UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the high toxicity and difficult metabolism of gold nanorods limit its clinical application prospects.

Method used

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  • A permeation-enhanced gold nanocluster drug-loaded targeting agent and its preparation method and application
  • A permeation-enhanced gold nanocluster drug-loaded targeting agent and its preparation method and application
  • A permeation-enhanced gold nanocluster drug-loaded targeting agent and its preparation method and application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0050] Example 1: Preparation and characterization of gold nanospheres (GNPs) and gold nanoclusters (GNCs) assembled by polypeptides

[0051] Take 100-200 μL of 20-30 mM chloroauric acid solution and 100-200 μL of sodium citrate solution in a 50 mL round-bottomed flask, add ultrapure water to dilute to a total volume of 20 mL, stir quickly, and take fresh ice water to prepare a concentration of 50-100 mM Quickly add 0.5-1mL sodium borohydride solution into a round-bottomed flask, stir rapidly at room temperature for 1-2 hours to obtain a gold nano-solution, use an ultrafiltration tube with a molecular weight cut-off of 10-25kDa to centrifuge to remove unreacted small molecules and concentrate , to obtain a gold nanosphere GNPs solution, which was stored in a 4°C refrigerator for later use.

[0052] Take 1~2×10 -9 mol gold nanosphere solution, weigh 2.5~3.5mg polypeptide (CRDPLGLAGDRC) and dissolve it in proper amount of ultrapure water, add it dropwise into the gold nanospher...

Embodiment 2

[0056] Example 2: Preparation of peptide-assembled gold nanocluster targeting agent (HER-GNCs) and preparation and characterization of peptide-assembled gold nanocluster drug-loaded targeting agent (HER-GNCs-DM1)

[0057] Take the prepared gold nanocluster GNCs solution and adjust the pH to 6-7, add the HER2 antibody solution dissolved in PBS, shake gently overnight at room temperature, and centrifuge with an ultrafiltration tube with a molecular weight cut-off of 300-500kDa to obtain the HER-GNCs solution , and stored in a 4°C refrigerator for later use.

[0058] Weigh an appropriate amount of free maytansine derivative DM1, dissolve and dilute it into 0.5-1 mg / mL mother solution with acetonitrile, take the prepared gold nanocluster GNCs, mix GNCs and DM1 according to the mass ratio of DM1 to gold as 1:1, and mix GNCs and DM1 at room temperature Stir for 12 h, and centrifuge using an ultrafiltration tube with a molecular weight cut-off of 10 kDa. Take the prepared GNCs-DM1, ...

Embodiment 3

[0062] Example 3: Photothermal conversion temperature rise curve of peptide-assembled gold nanocluster targeting preparation

[0063] Take 1 mL of GNPs, GNCs and HER-GNCs solution to make the Au concentration 100 μg / mL, use PBS as blank control, and use 3W / cm 2 The 808nm near-infrared laser was continuously irradiated for 20 minutes, and the temperature of the solution was measured with an infrared thermal imager at regular intervals, and a temperature change curve was drawn. The result is as Figure 5 shown.

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Abstract

The invention discloses a permeation-enhanced gold nanocluster drug-loaded targeting preparation and its preparation method and application. The targeting preparation includes gold nanoclusters, a cross-linking agent and a tumor treatment drug; wherein, the gold nanoclusters are composed of a cross-linking agent It is obtained by assembling gold nanospheres, and the surface of the gold nanoclusters is modified with a drug targeting tumor treatment of human epidermal growth factor receptor-2. The preparation can be used as an anti-tumor drug carrier, specifically targeted to the tumor, and the drug can be efficiently released at the tumor site through the reduction of the tumor microenvironment and NIR irradiation, and combined with hyperthermia and action to improve the therapeutic effect. The preparation of the present invention can also combine the advantages of gold in imaging such as CT imaging and photoacoustic imaging (PA) to perform medical diagnosis and achieve the purpose of precise diagnosis and treatment of multi-mode tumors.

Description

technical field [0001] The invention relates to the field of pharmaceutical preparations, in particular to a permeation-enhanced gold nano-cluster drug-loaded targeting preparation and its preparation method and application. Background technique [0002] Gold nanospheres refer to association colloids with a diameter between 1-150nm, which are usually prepared by reducing chloroauric acid. Gold nanoparticles have good biocompatibility, and their surface is easy to combine with various drugs or macromolecules through electrostatic adsorption, covalent or non-covalent bonding, etc., and can be used as a carrier for drug delivery systems. In addition, gold nanometers have high electron density, dielectric properties and optical properties, and can convert absorbed light energy into heat energy through surface plasmon resonance (SPR), which can be applied to cancer diagnosis, biological probes, photothermal Research areas such as therapy and radiosensitization. [0003] Phototh...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K41/00A61K49/22A61K47/52A61K47/62A61K31/5365A61K33/243A61K31/282A61K39/395A61K49/04A61K49/08A61K49/14A61K49/18A61P35/00B22F9/24B82Y40/00B82Y30/00
CPCA61K41/0052A61K49/221A61K49/222A61K47/52A61K47/62A61K31/5365A61K33/243A61K31/282C07K16/32A61K49/04A61K49/08A61K49/14A61K49/1824A61P35/00B22F9/24B82Y40/00B82Y30/00A61K2039/505
Inventor 沈雁涂家生叶子璇杨文倩刘彦滟
Owner CHINA PHARM UNIV
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