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Protein-dye complex and application thereof

A complex and dye technology, applied in protein-dye complex and its application field, can solve the problems of poor non-specific adsorption and targeting ability, low fluorescence quantum yield, limiting development and application, etc., achieving remarkable and strong effect Fluorescent performance, good biocompatibility effect

Active Publication Date: 2014-05-14
SUZHOU UNIV
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0004] Indocyanine green (ICG) has potential application in biomedicine due to its good optical absorption properties in the near-infrared region. In recent years, people have also used its absorption properties in photothermal therapy; however, some physical characteristics, Such as early aggregation at high concentration, poor stability, non-specific adsorption and poor targeting ability, etc. limit its development and application in biomedicine
[0005] The heptamethine indocyanine dye structure is similar to ICG and has strong optical absorption properties in the near-infrared region, and the fluorescence quantum yield is very low (<1%). It has been reported in the literature that the heptamethine indocyanine dye molecule is used for Photothermal therapy; however, it has not been reported to combine it with albumin to prepare a metabolizable non-toxic small particle and use the particle to prepare cancer imaging diagnosis and treatment preparations

Method used

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  • Protein-dye complex and application thereof
  • Protein-dye complex and application thereof
  • Protein-dye complex and application thereof

Examples

Experimental program
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Effect test

Embodiment 1

[0035] Example 1: Preparation of protein HSA-IR825 protein-dye complex loaded with organic fractions

[0036] Using albumin HSA as the substrate, small organic molecules are adsorbed into HSA through hydrophobic interaction to form HSA-IR825. Specifically include the following steps:

[0037] 1. Synthesize a certain amount of organic small molecule IR825, and its preparation method is as follows:

[0038] (1) Mix 2,3,3-trimethyl-4-2,5-benzo-3H-indole (TMBI, 10.0g, 48mmol) and α-bromo-p-toluic acid (BTA, 12.3g, 57mmol ) was dissolved in 40ml of dichlorobenzene and stirred at 110°C for 4h, after filtration, the crude product was purified and recrystallized with methanol to obtain intermediate 1;

[0039](2) Phosphorus oxychloride (37ml) and anhydrous dichloromethane (35ml) were added to the flask, and the solution was added dropwise to 80ml of DMF / dichloromethane mixture (1 / 1, V / V), followed by dropwise addition of cyclohexanone. The ice / water was removed, and the solution ...

Embodiment 2

[0043] Example 2: Research on the quantum yield of HSA-IR825 under different lasers

[0044] In order to further study the fluorescence intensity of HSA-IR825 under different laser irradiation, we measured the quantum yield under 600nm and 808nm laser excitation respectively. We selected rhodamine B (RHB) with a known quantum yield of 89% and indocyanine green ICG with a quantum yield of 4% under the two kinds of laser irradiation respectively as standards. HI =Y RhB *(F HI / F RhB )*(A RhB / A HI ), Y HI =Y ICG *(F HI / F ICG )*(A ICG / A HI ) to calculate the quantum yield of HSA-IR825 respectively under two kinds of laser excitation; Y HI , F HI 、A HI are the quantum yield, fluorescence intensity and absorbance of HSA-IR825, Y RhB , F RhB 、A RhB Respectively, the quantum yield, fluorescence intensity, and absorbance of rhodamine, Y ICG , F ICG 、A ICG are the quantum yield, fluorescence intensity, and absorbance of indocyanine green, respectively.

[0045] T...

Embodiment 3

[0046] Example 3: Testing of the heating curve of HSA-IR825 under laser irradiation

[0047] Put 2ml of HSA-IR825 aqueous solution with different concentrations in the cuvette, and 808nm laser (power 0.8 W / cm 2 ) directly irradiates the sample, and uses an infrared thermal imager to test its temperature change curve. The results are attached Image 6 As shown, within 5 minutes, as the concentration of HSA-IR825 increases, the temperature of the solution increases more significantly, indicating that the photothermal properties of HSA-IR825 have a strong concentration dependence; There was basically no change under irradiation. This shows that the HSA-IR825 complex has relatively strong optical absorption properties and can be used as a material for photothermal therapy.

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Abstract

The invention discloses a protein-dye complex and an application thereof. The protein-dye complex comprises human serum albumin and a heptamethine Indocyanine derivative, wherein human serum albumin is used as a carrier, the heptamethine cyanine derivative is adsorbed on the carrier via hydrophobic interaction; the molar ratio of human serum albumin to the heptamethine cyanine derivative is 1:1; the human serum albumin has a molecular weight of 69 KDa; the heptamethine cyanine derivative has a molecular weight of 983.5 Da; and the protein-dye complex has a particle size of 8-10 nanometers. The nanoparticle has high optical absorption property in near-infrared region and strong fluorescence in visible light region, has good dispersibility, and can be used for preparing cancer imaging diagnosis and treatment preparations.

Description

technical field [0001] The invention relates to a protein-dye complex and application thereof, belonging to the field of biomedicine. Background technique [0002] Cancer is one of the major malignant diseases that threaten human health. Although a large amount of human, material and financial resources have been invested in the prevention and treatment of cancer for decades since the 1950s, the progress made by human beings in this regard is very limited. [0003] The recent development of photothermal therapy has attracted more and more attention. The main principle is that some substances with good light absorption will generate high heat under laser irradiation after being swallowed by cells, which can kill tumor cells. Because near-infrared light has a strong ability to penetrate human tissues, the main components of human tissues such as water have poor absorption ability to near-infrared light. Therefore, compared with traditional treatment methods, photothermal the...

Claims

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Application Information

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IPC IPC(8): A61K49/00A61K41/00A61K47/42A61P35/00
Inventor 刘庄陈倩
Owner SUZHOU UNIV
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