Acoustic Characterization of Echogenic Polymersomes Prepared From Amphiphilic Block Copolymers

Xia, Longfei; Karandish, Fataneh; Kumar, Krishna N.; Froberg, James; Kulkarni, Prajakta; Gange, Kara N.; Choi, Yongki; Mallik, Sanku; Sarkar, Kausik

doi:10.1016/j.ultrasmedbio.2017.10.011

Cited by 9 publications

(13 citation statements)

References 54 publications

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“…The enhancement decreased with time. However, the enhancement remains signicant even aer 3 minutes of exposure similar to what was observed for polymersomes by Xia et al 17 Presence of sonication during preparation didn't change the dynamics.…”

Section: Stability Under Ultrasoundsupporting

confidence: 81%

“…A setup similar to what was used previously 17,24,50 was employed to characterize the acoustic scattering behavior of the echogenic exosomes (Fig. 1).…”

Section: Linear and Nonlinear Acoustic Characterizationmentioning

confidence: 99%

“…15,16 Previously, we have performed detailed acoustic characterizations of echogenic nanoparticles (i.e., liposomes and polymersomes) by varying their properties and shell chemistry. [17][18][19][20][21] Tracing diagnostic nanoparticles has revealed rapid nanoparticle clearance rates and adverse immune responses as the point of failure for many clinical trials. 22 However, unlike synthetic nanoparticles, many exosomes do not face these same issues potentially making them a more viable option for clinical drug delivery and diagnostics.…”

Section: Introductionmentioning

confidence: 99%

“…3,23 Combining the advantages of naturally derived exosomes to make the particle echogenic is a particularly exciting approach to demonstrate the utility of exosomes in biomedical research. 17,18,[24][25][26][27] Ultrasound is known as a safe, inexpensive, and real-time imaging modality. However, it suffers from low contrast.…”

Section: Introductionmentioning

confidence: 99%

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Echogenic exosomes as ultrasound contrast agents

et al. 2020

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Section: Stability Under Ultrasoundsupporting

confidence: 81%

“…A setup similar to what was used previously 17,24,50 was employed to characterize the acoustic scattering behavior of the echogenic exosomes (Fig. 1).…”

Section: Linear and Nonlinear Acoustic Characterizationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Echogenic exosomes as ultrasound contrast agents

et al. 2020

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“…Shrinking conventional ultrasound contrast agents to the nanoscale consolidates with them the abilities of traditional nanoparticles, bringing new possibilities 16 . Broadly, this class of submicron ultrasound agents 16 includes echogenic liposomes 17 - 19 , polymersomes 20 , gas vesicles 21 - 23 , cavitation seeds 14 , 24 , nanodroplets 15 , 25 , 26 , and nanobubbles 27 - 29 .…”

Section: Introductionmentioning

confidence: 99%

Concurrent visual and acoustic tracking of passive and active delivery of nanobubbles to tumors

et al. 2020

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Background: There has been growing interest in nanobubbles for their potential to extend bubble-mediated ultrasound approaches beyond that of their larger microbubble counterparts. In particular, the smaller scale of nanobubbles may enable them to access the tumor extravascular compartment for imaging and therapy in closer proximity to cancer cells. Compelling preliminary demonstrations of the imaging and therapeutic abilities of nanobubbles have thus emerged, with emphasis on their ability to extravasate. However, studies to date rely on indirect histologic evidence that cannot confirm whether the structures remain intact beyond the vasculature - leaving their extravascular potential largely untapped. Methods: Nanobubble acoustic scattering was assessed using a recently reported ultra-stable formulation at low concentration (10 6 mL -1 ) and frequency (1 MHz), over a range of pressures (100-1500 kPa) in a channel phantom. The pressure-dependent response was utilized as a basis for in vivo experiments where ultrasound transmitters and receivers were integrated into a window chamber for simultaneous intravital multiphoton microscopy and acoustic monitoring in tumor-affected microcirculation. Microscopy and acoustic data were utilized to assess passive and active delivery of nanobubbles and determine whether they remained intact beyond the vasculature. Results: Nanobubbles exhibit pressure-dependent nonlinear acoustic scattering. Nanobubbles are also found to have prolonged acoustic vascular pharmacokinetics, and passively extravasate intact into tumors. Ultrasound stimulation of nanobubbles is shown to actively enhance the delivery of both intact nanobubbles and shell material, increasing their spatial bioavailability deeper into the extravascular space. A range of acute vascular effects were also observed. Conclusion: This study presents the first direct evidence that nanobubbles passively and actively extravasate intact in tumor tissue, and is the first to directly capture acute vascular events from ultrasound-stimulation of nanobubbles. The insights gained here demonstrate an important step towards unlocking the potential of nanobubbles and extending ultrasound-based applications.

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