Inflammation targeting and microenvironment responsive nano system and preparation method and application thereof

A micro-environment and responsive technology, applied in the field of molecular imaging, can solve the problems of inability to find epileptic lesions, patients cannot undergo surgical treatment, and poor results, so as to improve the effect of material imaging and treatment, and has a good biological application prospect. The effect of improving the accuracy and safety of treatment

Active Publication Date: 2020-08-11
AFFILIATED HUSN HOSPITAL OF FUDAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, in 18% to 43% of patients with epilepsy who have undergone surgical treatment, no clear epileptic focus can be found on MRI.
Patients with negative MRI results are often ineligible for surgery, and the outcome is often poor

Method used

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  • Inflammation targeting and microenvironment responsive nano system and preparation method and application thereof
  • Inflammation targeting and microenvironment responsive nano system and preparation method and application thereof
  • Inflammation targeting and microenvironment responsive nano system and preparation method and application thereof

Examples

Experimental program
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Effect test

preparation example Construction

[0056] Its preparation method comprises the following steps:

[0057] A. BSA-MnO 2 Preparation of nanoparticles: configure albumin BSA aqueous solution (5-40mg / ml), (100-200rad / min) and slowly add MnCl under vigorous stirring 2 solution, (albumin and MnCl 2 The weight ratio is 1:5~1:40), and the stirring time is 5min. Use NaOH (0.1 uM) to adjust the pH of the solution to pH = (10-12), and react (1-4 hours) under vigorous stirring (25-40° C.).

[0058] BSA-MnO was obtained by dialysis in ultrapure water for 48 hours using a 10kDa molecular weight (MWCO) dialysis bag to remove excess precursors 2 Nanoparticles (BM).

[0059] B. BSA-MnO 2 - Preparation of CD163 short peptide nanoparticles: Take 28-32 parts of NHS-PEG-MAL into the aqueous solution of BM and stir for 1 hour at ambient temperature to form PEGylated BSA-MnO 2 .

[0060] Excess unattached PEG was removed using 10 kDa molecular weight (MWCO) ultrafiltration tubes.

[0061] C. Add 4-6 parts of CD163 short peptid...

Embodiment 1

[0064] An inflammation-targeting and microenvironment-responsive nanosystem, comprising the following components in parts by weight: 60 parts of nanocarriers; 8 parts of manganese dioxide; 30 parts of polyethylene glycol; and 5 parts of targeting functional molecules. The targeting functional molecule is CD163 targeting binding short peptide, the nanocarrier is albumin, and the albumin is bovine serum albumin; the active groups of albumin include carboxyl, thiol and amino groups. Manganese dioxide is the core crystal; polyethylene glycol is located on the surface of the nanocarrier, and the targeting functional molecule is connected to the polyethylene glycol on the surface of the nanocarrier through covalent linkage, and the core crystal is entrapped in a biomineralized manner. inside the nanocarrier. The molecular weight of polyethylene glycol is 3400; the particle size of the nano system is 25nm.

[0065] Such as figure 1 Shown; Its preparation method comprises the steps:...

Embodiment 2

[0076] Application of an inflammation-targeting and microenvironment-responsive nanosystem:

[0077] Using 250nM dexamethasone to stimulate J774A.1 cells for 24 hours to induce J774A.1 macrophages to construct CD163+ cell model, the results are as follows Figure 5 Shown: Figure 4 The indicated dexamethasone can induce high expression of CD163 protein in J774A.1 cells.

[0078] Coumarin-6-labeled BMC / BMP (200ug / mL) was co-incubated with J774A.1 cells in dexamethasone-induced group and non-dexamethasone-induced group for 15 minutes, respectively. Then take the J774A.1 cells induced by dexamethasone and set up another free CD163 short peptide group, that is, after adding BSA-MNO 2 -Before incubation of CD163 short peptide nanoparticles (BMC), add CD163 short peptide (200ug / mL) and incubate for 15 minutes in advance. The target binding ability of BMC to CD163 was verified in vitro by using immunofluorescence confocal imaging and flow cytometry analysis. The results are as fol...

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Abstract

The invention discloses an inflammation targeting and microenvironment responsiveness nano system as well as a preparation method and application thereof, and relates to the technical field of molecular imaging. The nano system comprises a targeting functional molecule, a nano carrier and a core crystal, the targeting functional molecule is CD163 targeting binding oligopeptide, and the oligopeptide is connected with polyethylene glycol on the surface of the nanoparticle in a covalent connection manner; and the core crystal is entrapped in the nano-carrier in a biomineralization manner. After intravenous injection of the nanosystem, the targeted CD163 positive macrophages are enriched in epilepsy focuses and react with H < + > and H2O2, so that magnetic resonance T1 signals of the epilepsyfocuses are enhanced and imaged, idiopathic / cryptogenic epilepsy focuses are accurately and visually displayed, and clinical improvement of treatment accuracy and safety is facilitated; active oxygensubstances in epileptic focuses can be catalytically removed, oxidative stress is relieved, oxygen is generated, the local hypoxic microenvironment is improved, and the neuron activity of epileptic regions is protected.

Description

technical field [0001] The invention relates to the technical field of molecular imaging, and relates to an inflammation-targeting and microenvironment-responsive nano-system and its preparation method and application, in particular to an inflammation-targeting and microenvironment-responsive nano-medicine system for brain epileptic foci and its Preparation and application. Background technique [0002] Epilepsy is one of the most common chronic neurological diseases, characterized by recurrent seizures caused by abnormal discharge of brain neurons. About 65 million people worldwide suffer from epilepsy, and the impact of epilepsy on the health and quality of life of patients and the whole society is extremely serious. There is currently no drug that can cure epilepsy, and the disease usually stays with the patient for life. [0003] Most of the existing antiepileptic drugs are symptomatic drugs with many side effects and are ineffective in 30-40% of patients. Surgical re...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K49/14A61K49/12A61K49/18A61K47/62A61K47/69A61K47/64A61K47/42A61K45/00A61P25/08B82Y5/00B82Y15/00
CPCA61K49/14A61K49/143A61K49/126A61K49/186A61K49/1866A61K49/1869A61K47/62A61K47/6935A61K47/643A61K47/42A61K45/00A61P25/08B82Y5/00B82Y15/00
Inventor 张军林霖王剑虹庞志清耿道颖
Owner AFFILIATED HUSN HOSPITAL OF FUDAN UNIV
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