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

Lipid nano-scale ultrasound contrast agent for targeting tumor-associated macrophages as well as preparation method and application thereof

A technology for ultrasound contrast agents and macrophages, which is applied in echo/ultrasound imaging agents, antineoplastic drugs, and liposome delivery, and can solve problems such as nanoscale ultrasound contrast agents that have not yet been seen

Inactive Publication Date: 2020-05-15
SHANDONG UNIV QILU HOSPITAL
View PDF1 Cites 4 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

So far, there has been no research on TAM-targeted nanoscale ultrasound contrast agents

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
  • Lipid nano-scale ultrasound contrast agent for targeting tumor-associated macrophages as well as preparation method and application thereof
  • Lipid nano-scale ultrasound contrast agent for targeting tumor-associated macrophages as well as preparation method and application thereof
  • Lipid nano-scale ultrasound contrast agent for targeting tumor-associated macrophages as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0059] Example 1: Preparation of Lipid Nanoscale Ultrasonic Contrast Agent

[0060] A method for preparing a lipid nanoscale ultrasound contrast agent targeting tumor-associated macrophages, comprising the following steps:

[0061] (1) Mix glycerin and phosphate buffer at a volume ratio of 1:9 to make a hydration solution, take 0.4mL propylene glycol and 0.4mL hydration solution into a 1.5mL EP tube, add lipid, and the lipid is 0.7 mg dipalmitoylphosphatidylcholine (DPPC), 0.2 mg distearoylphosphatidylethanolamine (DSPE), 0.4 mg distearoylphosphatidylethanolamine-polyethylene glycol-folate (DSPE-PEG-FOL), additionally , in order to observe the structure of nano-scale ultrasound contrast agent under a fluorescence microscope, add 0.1mg of distearoylphosphatidylethanolamine-polyethylene glycol-fluorescein isothiocyanate (DSPE-PEG-FITC) to obtain a suspension ;

[0062] (2) Pass perfluoropropane into the suspension in step (1) to replace the air, place the EP tube in a constant...

Embodiment 2

[0068] Example 2: Establishing a tumor-associated macrophage model

[0069] The tumor-associated macrophage model was established by culturing RAW264.7 macrophages in conditioned medium. In order to verify the successful activation of RAW264.7 macrophages into tumor-associated macrophages, the morphological changes were observed using a light microscope, and real-time Fluorescent quantitative polymerase chain reaction determined whether the expression of tumor-associated macrophage-associated genes mrc1, il10, nos2 and tnf was upregulated. The culture supernatant of the mouse Lewis lung cancer cells was collected and filtered with a 0.22 μm membrane filter to obtain the conditioned medium. In order to optimize the conditions for the activation of RAW264.7 macrophages into tumor-associated macrophages, different concentrations (0%, 50%, 100%) of conditioned medium were used to treat RAW264 at different time points (0, 24, 48, 72h). .7 macrophages and genetic testing.

[0070]...

Embodiment 3

[0073] Example 3: Biosafety Evaluation of Nanoscale Ultrasound Contrast Agents

[0074] The tumor-associated macrophages obtained in Example 2 were mixed with 1×10 4 Inoculate each well in a 96-well plate, add culture medium, 37°C, 5% CO 2 After incubation for 24 hours, two sets of experiments were carried out. In the first set of experiments, the medium of tumor-associated macrophages was replaced with fresh medium containing lipids. The concentrations of lipids in the fresh medium were 25, 50, and 100 , 200, 300 μg / mL, the contained lipids are divided into two situations, one is that the lipids are dipalmitoylphosphatidylcholine (DPPC), distearoylphosphatidylethanolamine (DSPE) and two Stearoylphosphatidylethanolamine-polyethylene glycol-folic acid (DSPE-PEG-FOL), its mass ratio is 7:2:4, a kind of is that described lipid is dipalmitoylphosphatidylcholine (DPPC) and Distearoylphosphatidylethanolamine (DSPE) with a mass ratio of 7:6; in the second set of experiments, the medi...

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
particle diameteraaaaaaaaaa
particle sizeaaaaaaaaaa
Login to View More

Abstract

The invention relates to a lipid nano-scale ultrasound contrast agent for targeting tumor-associated macrophages as well as a preparation method and application thereof. The lipid nano-scale ultrasound contrast agent for the targeting tumor-associated macrophages disclosed by the invention takes lipids as a shell membrane material, and wraps low-molecular-weight hyaluronic acids and gaseous fluorocarbon in the shell membrane; and the lipids consist of dipalmitoyl-phosphatidylcholine (DPPC), distearoyl-phosphatidylethanolamine (DSPE) and distearyl phosphatidylethanolamine-polyethylene glycol-folic acids (DSPE-PEG-FOL). The lipid nano-scale ultrasound contrast agent has a particle size of 255-497 nm, and is capable of passing through vascular wall space of tumor tissue so as to achieve tumortreatment effects with passive targeting and high efficiency; PEG chain is utilized so as to have coupled folic acids located outside the lipids shell membrane and the low-molecular-weight hyaluronicacids wrapped in the contrast agent, so that it is ensured that the lipid nano-scale ultrasound contrast agent for the targeting tumor-associated macrophages can actively target the tumor-associatedmacrophages by a folic acid-folic acid receptor way; and the low-molecular-weight hyaluronic acids act on the tumor-associated macrophages, so that the tumor-associated macrophages can be transformedfrom type-M2 macrophages into type-M1 macrophages.

Description

technical field [0001] The invention relates to a lipid nanoscale ultrasonic contrast agent targeting tumor-associated macrophages, a preparation method and application thereof, and belongs to the technical field of ultrasonic molecular imaging. Background technique [0002] Macrophages exhibit continuous functional activation states under pathological conditions, and M1 and M2 types are used to represent the two extremes of macrophage activation states, and these two activation types play opposite roles in immune and inflammatory responses. Tumor associated macrophages (tumor associated macrophages, TAM) are a special type of M2 macrophages, which can promote the formation of tumor angiogenesis and the remodeling of extracellular matrix, thereby promoting the occurrence and metastasis of tumors. A major immune component in the environment that plays a crucial role in primary tumor initiation, spread, seeding, and proliferation in metastatic organs. In addition, the density...

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): A61K49/22A61K31/728A61K9/127A61K47/54A61K47/60A61P35/00
CPCA61K9/127A61K9/1277A61K31/728A61K47/54A61K47/60A61K49/221A61K49/227A61P35/00
Inventor 李杰孙霄郭鲁商蒙蒙时丹丹
Owner SHANDONG UNIV QILU HOSPITAL
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