Protease-sensitive fluorescent light and magnetism dual-response micro-capsule and preparation method thereof

A protease and responsive technology, applied in the field of fluorescent and magnetic dual-responsive microcapsules and their preparation, to achieve the effects of enhanced T2 relaxation efficiency and high MRI contrast intensity

Active Publication Date: 2014-08-06
上交(潍坊)新材料科技有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, assemblies that combine protease-sensitive near-infrared fluorescence imaging with MRI imaging have not been reported

Method used

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  • Protease-sensitive fluorescent light and magnetism dual-response micro-capsule and preparation method thereof
  • Protease-sensitive fluorescent light and magnetism dual-response micro-capsule and preparation method thereof

Examples

Experimental program
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Effect test

Embodiment 1

[0032] Example 1: Preparation of trypsin-sensitive fluorescent and magnetic dual-responsive microcapsules

[0033] a. To 2.5mL, 1mg / mL poly-L-lysine (M w ~65000) dropwise add 2.5mL, 0.025mg / mL ICG aqueous solution to the solution, incubate for 2h, then add 5mL, 3mg / mL sodium citrate solution to the solution, shake at 1000rpm for 10s, form a package of self-quenching fluorescence Molecular macromolecular aggregates in aqueous solution.

[0034] b. Add 2.5mL, 0.5mg / mL citric acid-coated Fe dropwise to the aggregate solution 3 o 4 Magnetic particles (the average particle size of the magnetic nanoparticles is 7nm, spherical in shape, prepared by thermal decomposition method and ligand exchange method), incubated with ultrasound (working frequency 40kHz) at room temperature for 20min, forming capsule walls coated with magnetic nanoparticles Microcapsule structure.

[0035] c. Add dropwise 1.5mL, 5mg / mL polyacrylic acid (M w ~1800) solution, incubate with ultrasound (working fr...

Embodiment 2

[0040] Example 2: Preparation of matrix metalloproteinase 2 / 9 sensitive fluorescent and magnetic dual-responsive microcapsules

[0041] a. To 2mL, 2mg / mL of PLG / LR (M w ~70000) solution, drop 1mL, 0.01mg / mLCy5.5 solution, and incubate at room temperature for 4h to form fluorescent agent-modified polypeptide macromolecules. Add 5mL, 3mg / mL ethylenediaminetetraacetic acid tetrasodium salt EDTA aqueous solution, and 0.5mL, 0.05mg / mL fluorescence quencher BHQ3 to the formed polypeptide aqueous solution, oscillate at 750rpm for 20s, and form an encapsulated fluorescence Polypeptide aggregates of reagents and fluorescence quenchers.

[0042] b. Add 2mL, 0.3mg / mL citric acid-coated Fe dropwise to the aggregate solution 3 o 4 Magnetic particles, (the average particle size of the magnetic nanoparticles is 7nm, spherical in shape, prepared by thermal decomposition and ligand exchange [1，2] ), ultrasonic (operating frequency 40kHz) at room temperature for 30min, to form a microcapsul...

Embodiment 3

[0048] Example 3: Preparation of Protease-3 Sensitive Fluorescent and Magnetic Double Responsive Microcapsules

[0049] a. To 1.5mL, 2mg / mL DEVD (M w ~50000) the polypeptide solution was added dropwise with 1 mL, 0.05 mg / mL ICG solution, and incubated at room temperature for 4 h to form fluorescent agent-modified polypeptide macromolecules. Add 7mL, 4mg / mL tetraasparagine sodium salt Na in the formed polypeptide aqueous solution 5 (ASP) 4 Aqueous solution, and 0.5mL, 0.05mg / mL fluorescence quencher NIRQ820, shake at 900rpm for 10s to form polymer peptide aggregates wrapping fluorescent agent and fluorescence quencher.

[0050] b. Add 2.5mL, 0.25mg / mL silicate-coated Fe dropwise to the aggregate solution 3 o 4 Magnetic particles (SiCOOH-Fe3O4 magnetic nanoparticles have an average particle size of 10nm and a spherical shape, prepared by thermal decomposition and ligand exchange methods), ultrasonic (working frequency 40kHz) at room temperature for 30min, to form a capsule w...

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Abstract

The invention relates to a micron-sized protease-sensitive near-infrared fluorescent light and magnetism dual-response micro-capsule. The micro-capsule is divided into an outer layer, a middle layer and an inner layer which are compactly combined; the outer layer comprises polymer molecules provided with electronegative functional groups and coated on the middle layer; the middle layer is a capsule wall of the micro-capsule, which is formed by wrapping and hybridizing a protease-sensitive positive ion peptide chain and magnetic nanoparticles; near-infrared fluorescent molecules and fluorescent quenching molecules are enveloped in the capsule wall; the inner layer is a capsule cavity of the micro-capsule; and the capsule cavity comprises one or a plurality of cavities which are separated by protease-sensitive positive ion peptide chain molecules. In tissues without specific proteases, real-time development and track of the micro-capsule can be finished through MRI (Magnetic Resonance Imaging) development enhancement; when reaching to tissues with specific proteases, the micro-capsule disintegrates and sends near-infrared fluorescent light, and meanwhile, MRI development is weakened; and therefore, the function of double targeted development of the micro-capsule is realized.

Description

technical field [0001] The invention relates to a microcapsule used in MRI imaging, in particular to a protease-sensitive fluorescent and magnetic double-responsive microcapsule and a preparation method thereof. Background technique [0002] In recent years, molecular imaging techniques have become an independent tool in modern diagnostic approaches. Molecular imaging is highly specific and can provide biological characterization at the molecular level in living systems. This technology can enable early diagnosis and tracking of treatment process through visual monitoring of specific molecular activities in diseases. Different imaging modalities, such as optical fluorescence imaging, magnetic resonance imaging (MRI), contrast-enhanced ultrasound, etc., have been successfully applied in the field of medical molecular imaging. In the study of optical fluorescence imaging, near-infrared fluorescent probes have become the main research objects in the field of in vivo imaging d...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K49/18A61K49/14A61K49/00
Inventor 窦红静孙康宋晟蒋泽权
Owner 上交(潍坊)新材料科技有限公司
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