Targeting opto-acoustic contrast agent as well as preparation method and application thereof

A photoacoustic contrast, targeting technology, applied in the field of imaging diagnostic drugs, can solve the problem of non-specific targeting, and achieve the effect of good targeting specificity and broad clinical application prospects.

Active Publication Date: 2014-08-06
THE NAT CENT FOR NANOSCI & TECH NCNST OF CHINA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The contrast agents currently reported for photoacoustic contrast imaging include carbon materials (such as carbon nanotubes, etc.), gold nanomaterials (such as gold rods, etc.), and a class of near-infrared molecules (such as indocyanine green ICG, etc.), but They are not specifically targeted for in vivo diagnostic imaging of bacterial infections

Method used

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  • Targeting opto-acoustic contrast agent as well as preparation method and application thereof
  • Targeting opto-acoustic contrast agent as well as preparation method and application thereof
  • Targeting opto-acoustic contrast agent as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0061] Example 1 Preparation of targeted photoacoustic contrast agent of the present invention

[0062] Using pyropheophytin a as the photoacoustic signal molecule and the polypeptide with the sequence Pro-Lys-Gly-Val-Arg-Gly as the connecting polypeptide, the synthesis of the targeted photoacoustic contrast agent of the present invention is carried out according to the following steps:

[0063] (1) Synthesis of Linked Peptides

[0064] Synthesis of linked peptides by Fmoc solid-phase synthesis:

[0065] A Wang resin with a modification density of 0.35 mM was selected for synthesis, in which the N-terminal of the first amino acid (glycine) was protected by Fmoc, and the C-terminal was fixed on the resin. Use 20% (v / v) hexahydropyridine in DMF to remove the Fmoc protection at the N-terminal, and then use the ninhydrin test to test the deprotection result. Then the carboxyl group of the next amino acid was treated with 0.4M 4-methylmorpholine (NMM) and 0.4M benzotriazole-N,N,N...

Embodiment 2

[0074] Example 2 Specific bacterial targeting of the photoacoustic contrast agent of the present invention

[0075] Select Staphylococcus aureus and Staphylococcus epidermidis as model strains of Gram-positive bacteria, Pseudomonas aeruginosa, Serratia, Escherichia coli and Proteus as model strains of Gram-negative bacteria, and the concentration was 1×10 8 CFU bacterial culture solution and 40 μM of the photoacoustic contrast agent of the present invention prepared in Example 1 were co-incubated for 30 minutes in equal volume, and the contrast agent without targeted adsorption was washed with PBS, and the isolated bacterial cells were sampled and observed by laser confocal microscope Specific targeted enrichment of Gram-positive bacteria by photoacoustic contrast agents.

[0076] The result is as Image 6 as shown, Image 6 The results show that the photoacoustic contrast agent of the invention has a specific targeted enrichment effect on Staphylococcus aureus and Staphyloc...

Embodiment 3

[0077] Example 3 Imaging of bacterial infection in vivo by photoacoustic contrast agent of the present invention

[0078] Select 6-8 week old BALB / c mice and inject 1×10 8 CFU Staphylococcus aureus culture solution for 48 hours to form a mouse hind leg myositis model. Inject 200 μL of a photoacoustic contrast agent with a concentration of 200 μM through the tail vein, and select time points of 1, 4, 8, 12 and 24 hours to observe the imaging of myositis infection at different time points, and construct a 3D model of muscle infection in mice. The result is as Figure 7 shown.

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Abstract

The invention discloses a targeting opto-acoustic contrast agent. The targeting opto-acoustic contrast agent sequentially comprises a fat-soluble opto-acoustic signal molecule, a connecting polypeptide and a water-soluble targeting molecule. The targeting opto-acoustic contrast agent disclosed by the invention is an amphipathic molecule, can form a stable aggregate with good water solubility and has the characteristics of ultraviolet absorption red shift, fluorescence quenching and opto-acoustic signal enhancement. The targeting opto-acoustic contrast agent can be enriched at an inflammation part infected by gram-positive bacteria in vivo in a targeting peculiar manner, realizes the defection of gram-positive bacteria infection in vivo and has very good clinical application prospect.

Description

technical field [0001] The invention relates to the technical field of drugs for imaging diagnosis, in particular to a targeted photoacoustic contrast agent, its preparation method and application. Background technique [0002] Diseases caused by bacterial infections are diseases with high morbidity and mortality in the world. In clinical treatment, doctors' treatment of infection is mainly based on blood examination. The data provided by this single detection method is not enough to guide doctors to make accurate judgments, so most doctors mainly choose antibiotics for treatment based on their own experience. This situation not only leads to the abuse and overuse of antibiotics, but also may delay the treatment of diseases due to wrong antibiotics, leading to serious consequences of death. [0003] In addition, the medical implantation process with a high incidence of bacterial infection is also unable to effectively prevent the formation of bacterial biofilms on implanted...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K49/00
Inventor 王浩李莉莉马怀雷
Owner THE NAT CENT FOR NANOSCI & TECH NCNST OF CHINA
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