US 12,133,891 B2
Microbubble-extracellular vesicle complexes
Eun Pyo Choi, Gwangju (KR); Jong Oh Park, Gyeonggi-do (KR); Chang Sei Kim, Gwangju (KR); You Hee Choi, Gwangju (KR); Byung Jeon Kang, Gwangju (KR); Ho Yong Kim, Gwangju (KR); Hyeong Woo Song, Jeollanam-do (KR); Dae Won Jung, Gwangju (KR); Han Sol Lee, Gyeonggi-do (KR); Deok Ho Kim, Ellicott City, MD (US); and Min Jae Do, Baltimore, MD (US)
Assigned to INDUSTRY FOUNDATION OF CHONNAM NATIONAL UNIVERSITY, Gwangju (KR); KOREA INSTITUTE OF MEDICAL MICROROBOTICS, Gwangju (KR); and Johns Hopkins University, Baltimore, MD (US)
Filed by Industry Foundation of Chonnam National University, Gwangju (KR); Korea Institute of Medical Mcrorobotics, Gwangju (KR); and Johns Hopkins University, Baltimore, MD (US)
Filed on Nov. 2, 2021, as Appl. No. 17/517,621.
Prior Publication US 2023/0136448 A1, May 4, 2023
Int. Cl. A61K 47/69 (2017.01); A61K 41/00 (2020.01); A61K 47/64 (2017.01); A61N 7/00 (2006.01)
CPC A61K 41/0028 (2013.01) [A61K 47/64 (2017.08); A61K 47/6911 (2017.08); A61N 2007/0078 (2013.01)] 1 Claim
 
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.