Echogenic exosomes as ultrasound contrast agents

Jenna Osborn; Jessica E. Pullan; James Froberg; Jacob Shreffler; Kara N. Gange; Todd Molden; Yongki Choi; Amanda Brooks; Sanku Mallik; Kausik Sarkar

doi:10.1039/d0na00339e

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Echogenic exosomes as ultrasound contrast agents

Journal article

Open access

Peer reviewed

Echogenic exosomes as ultrasound contrast agents

Jenna Osborn, Jessica E. Pullan, James Froberg, Jacob Shreffler, Kara N. Gange, Todd Molden, Yongki Choi, Amanda Brooks, Sanku Mallik and Kausik Sarkar

Nanoscale advances, Vol.2(8), pp.3411-3422

08/01/2020

DOI: 10.1039/d0na00339e

PMCID: PMC9410358

PMID: 36034734

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Abstract

Exosomes are naturally secreted extracellular bilayer vesicles (diameter 40-130 nm), which have recently been found to play a critical role in cell-to-cell communication and biomolecule delivery. Their unique characteristics-stability, permeability, biocompatibility and low immunogenicity-have made them a prime candidate for use in delivering cancer therapeutics and other natural products. Here we present the first ever report of echogenic exosomes, which combine the benefits of the acoustic responsiveness of traditional microbubbles with the non-immunogenic and small-size morphology of exosomes. Microbubbles, although effective as ultrasound contrast agents, are restricted to intravascular usage due to their large size. In the current study, we have rendered bovine milk-derived exosomes echogenic by freeze drying them in the presence of mannitol. Ultrasound imaging and direct measurement of linear and nonlinear scattered responses were used to investigate the echogenicity and stability of the prepared exosomes. A commercial scanner registered enhancement (28.9% at 40 MHz) in the brightness of ultrasound images in presence of echogenic exosomes at 5 mg mL(-1). The exosomes also showed significant linear and nonlinear scattered responses-11 dB enhancement in fundamental, 8.5 dB in subharmonic and 3.5 dB in second harmonic all at 40 mg mL(-1) concentration. Echogenic exosomes injected into the tail vein of mice and the synovial fluid of rats resulted in significantly higher brightnessas much as 300%-of the ultrasound images, showing their promise in a variety of in vivo applications. The echogenic exosomes, with their large-scale extractability from bovine milk, lack of toxicity and minimal immunogenic response, successfully served as ultrasound contrast agents in this study and offer an exciting possibility to act as an effective ultrasound responsive drug delivery system.

Chemistry

Chemistry, Multidisciplinary

Materials Science

Materials Science, Multidisciplinary

Nanoscience & Nanotechnology

Physical Sciences

Science & Technology

Science & Technology - Other Topics

Technology

Details

Title: Subtitle: Echogenic exosomes as ultrasound contrast agents
Creators: Jenna Osborn - George Washington University
Jessica E. Pullan - North Dakota State University
James Froberg - North Dakota State University
Jacob Shreffler - North Dakota State University
Kara N. Gange - North Dakota State University
Todd Molden - North Dakota State University
Yongki Choi - North Dakota State University
Amanda Brooks - North Dakota State University
Sanku Mallik - North Dakota State University
Kausik Sarkar - George Washington University
Resource Type: Journal article
Publication Details: Nanoscale advances, Vol.2(8), pp.3411-3422
DOI: 10.1039/d0na00339e
PMID: 36034734
PMCID: PMC9410358
NLM abbreviation: Nanoscale Adv
ISSN: 2516-0230
eISSN: 2516-0230
Publisher: Royal Soc Chemistry
Number of pages: 12
Grant note: ARCS MWC Chapter 1 R01GM 114080 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA Myers family McNichols Family Foundation
Language: English
Date published: 08/01/2020
Academic Unit: Orthopedics and Rehabilitation
Record Identifier: 9984304692102771

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