Microbubble-extracellular vesicle complexes

Patent metadata

Field	Value
Publication number	US-12133891-B2
Application number	US-202117517621-A
Country	US
Kind code	B2
Filing date	Nov 2, 2021
Priority date	Nov 2, 2021
Publication date	Nov 5, 2024
Grant date	Nov 5, 2024

Abstract

Disclosed herein are a microbubble-extracellular vesicle complex, a production method therefor, and a system for driving the same. In one aspect, preferred microbubble-extracellular vesicle complexes may comprise an ultrasound contrast agent-based microbubble, an extracellular cell derived from a natural killer cell (NK cell), a human glial cell, or a human mesenchymal stem cell, and a coupling medium and can be derive in a 3D mode using ultrasonic waves and deliver a drug loaded in the extracellular vesicle to a target site.

First claim

What is claimed is:

1. A system for driving a microbubble-extracellular vesicle complex for treating hepatocellular carcinoma, the system comprising:
a) a plurality of ultrasonic transducers wherein the plurality of ultrasonic transducers are configured to apply an ultrasound wave to the microbubble-extracellular vesicle complex to form a focal point, wherein the plurality of ultrasonic transducers are arranged hemispherically and consists of 16 immersion-type ultrasonic transducers, each having a diameter of 16 mm and a resonance frequency of 1 MHz;
b) a microbubble-extracellular vesicle complex; and
c) a therapeutic agent,
wherein the microbubble is a gas-filled microsphere and comprises phosphatidylcholine, biotin, and annexin V;
wherein the extracellular vesicle is derived from a natural killer cell (NK cell) and comprises biotin and N-hydroxysulfosuccinimide (sulfo-NHS);
wherein the biotin of the microbubble is coupled to the biotin of the extracellular vesicle by avidin;
wherein the therapeutic agent is doxorubicin;
wherein the microbubble-extracellular vesicle complex exhibits anti-tumor activity against hepatocellular carcinoma or Hep3B hepatocellular carcinoma cell lines; and
wherein the system is configured to deliver the doxorubicin to a target site by applying the ultrasound wave to rupture the microbubble and release the doxorubicin and cytotoxic proteins from the extracellular vesicle.

Assignees

• Univ Nat Chonnam Ind Found
• Korea Inst Of Medical Mcrorobotics
• Univ Johns Hopkins
• Korea Inst Of Medical Microrobotics

Inventors

• Choi Eun Pyo
• Park Jong Oh
• Kim Chang Sei
• Choi You Hee
• Kang Byung Jeon
• Kim Ho Yong
• Song Hyeong Woo
• Jung Dae Won
• Lee Han Sol
• Kim Deok Ho
• Do Min Jae

Classifications

• A61N2007/0078

  with multiple treatment transducers · CPC title

• A61K47/6911

  the form being a liposome · CPC title

• A61K47/64

  Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent (peptidic linkers A61K47/65) · CPC title

• A61B8/481

  involving the use of contrast agents, e.g. microbubbles introduced into the bloodstream · CPC title

• A61K49/223 Primary

  Microbubbles, hollow microspheres, free gas bubbles, gas microspheres · CPC title