Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Nano-drug carrier crossing blood cerebral barrier

A drug and mutant technology, applied in the intersection of bionics and biomedicine, in the field of nanobiology, can solve problems such as limiting the efficacy of brain diseases

Inactive Publication Date: 2018-09-07
KUNSHAN XINYUNDA BIOTECH CO LTD
View PDF2 Cites 9 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Because of its existence, 100% of macromolecular drugs and more than 98% of small molecule drugs cannot pass through and reach brain tissue, which greatly limits the efficacy of drugs on brain diseases [1-3]

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Nano-drug carrier crossing blood cerebral barrier
  • Nano-drug carrier crossing blood cerebral barrier
  • Nano-drug carrier crossing blood cerebral barrier

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0054] Example 1 Human H-ferritin specifically binds to human brain endothelial cells through the receptor TfR1

[0055] In order to study whether human H-ferritin specifically binds to human brain endothelial cells, human blood-brain barrier brain endothelial cells hCMEC / D3 (EMD Millipore Corporation: SCC066) were selected for research. In vitro, firstly, the present invention proves that the receptor TfR1 of H-ferritin is highly expressed on the human blood-brain barrier brain endothelial cells hCMEC / D3, and then human H-ferritin The protein was incubated, and the combination of human H-ferritin and tumor cells was detected by flow cytometry and laser confocal methods.

[0056] The experimental method is as follows:

[0057] a) Expression of TfR1 on human brain endothelial cells.

[0058] Culture human blood-brain barrier brain endothelial cells hCMEC / D3 to 1×10 5 About (100×20mm Petri dish, Corning, USA). The culture conditions were: EBM-2 medium (Gibco Life Technologie...

Embodiment 2

[0061] Example 2 Subcellular localization of human H-ferritin after entering human brain endothelial cells

[0062] The classic intracellular pathway of TfR1: After binding to the ligand, the receptor TfR1 mediates endocytosis, enters the endosome (endosome), and then enters the lysosome (lysosome). In order to realize the crossing of the human blood-brain barrier, the first problem to be solved is whether the ligand can enter the lysosome after binding to TfR1. The present invention proves for the first time that in human brain endothelial cells, most H-ferritin does not co-localize with lysosomes, but exists in the form of endosomes, thus providing intracellular localization support for crossing the blood-brain barrier .

[0063] The specific experimental method is as follows:

[0064] a) Human H-ferritin can be effectively endocytosed by human blood-brain barrier brain endothelial cells

[0065] Human blood-brain barrier brain endothelial cell hCMEC / D3 slides (BD Bioscie...

Embodiment 3

[0068]Example 3 Human H-ferritin can effectively cross the human blood-brain barrier model

[0069] a) Establishment of blood-brain barrier model

[0070] Human blood-brain barrier brain endothelial cells hCMEC / D3 (2×10 4 / well) inoculated on gelatin (10 μg / cm 2 ) pretreated Transwell plate (3 μm pore size, Corning, USA) (the culture conditions are the same as in Example 1). 37 degrees Celsius CO 2 Culture in an incubator until confluent (2-3 days). After observing under a microscope that hCMEC / D3 reached confluence, the medium (EBM-2 medium) was added to the chamber on the Transwell plate, so that the difference between the upper and lower chambers was greater than 0.5 cm. After 4 hours, if there is still a significant liquid level difference between the two chambers, it is considered to have been completely confluent. Transwell wells not seeded with cells were used as blank control. At this point, it is considered that the blood-brain barrier model was constructed succ...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

PropertyMeasurementUnit
diameteraaaaaaaaaa
Login to View More

Abstract

The invention discloses a nano-drug carrier crossing the blood cerebral barrier. The carrier can target brain lesions (brain tumors or other neurodegenerative diseases). The targeting drug carrier crossing the blood cerebral barrier contains all-heavy-chain human ferritin or a reconstruct or mutant of a functional fragment thereof. The carrier crosses the blood brain barrier via receptor-mediatedtranscytosis. The nano-drug carrier of the invention is expected to be an effective nano-drug carrier for the treatment of brain tumors or neurodegenerative diseases.

Description

technical field [0001] The invention belongs to the intersecting fields of nanobiology, bionics and biomedicine. In particular, the present invention relates to a nano-drug delivery system capable of crossing the blood-brain barrier and actively targeting brain lesions, the delivery system comprising full heavy chain human ferritin or its functional fragment reconstruction or mutant . Background technique [0002] The Blood-Brain Barrier (BBB) ​​is an international problem in the treatment of brain diseases. Because of its existence, 100% of macromolecular drugs and more than 98% of small molecule drugs cannot pass through and reach brain tissue, which greatly limits the efficacy of drugs on brain diseases [1-3] . Therefore, the discovery of a drug that can effectively penetrate the blood-brain barrier has been highly anticipated. [0003] The blood-brain barrier is a special structure mainly composed of brain capillary endothelial cells, sticky ends of astrocytes and ti...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Applications(China)
IPC IPC(8): C07K14/47A61K51/08A61K45/00A61K31/704A61P25/00A61P35/00A61P25/28A61P25/16A61P9/10A61P25/08A61P25/14A61P35/02A61P21/00
CPCA61K45/00A61K47/42A61K51/08A61K31/704C07K14/47A61P9/10A61P21/00A61P25/00A61P25/08A61P25/14A61P25/16A61P25/28A61P35/00A61P35/02A61K9/5169A61K38/00A61K45/06
Inventor 阎锡蕴范克龙周萌
Owner KUNSHAN XINYUNDA BIOTECH CO LTD
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com