&lt;p&gt;G250 Antigen-Targeting Drug-Loaded Nanobubbles Combined with Ultrasound Targeted Nanobubble Destruction: A Potential Novel Treatment for Renal Cell Carcinoma&lt;/p&gt;

Yu, Zhiping; Wang, Yixuan; Xu, Dan; Zhu, Lianhua; Hu, Ming; Liu, Qiuli; Lan, Weihua; Jiang, Jun; Wang, Luofu

doi:10.2147/ijn.s230879

Cited by 27 publications

(12 citation statements)

References 30 publications

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“…While destructive probes do not provide spatial information on detected cavitation, aside from that inferred from behavior and time delays, it is possible that active delivery enhances intact NB penetration into tumors under the tested conditions: Indeed it has recently been shown that targeted NBs under ultrasound exposure are able to achieve deep penetration into rabbit clots, and with greater efficacy than stimulated MBs 67 . Ultrasound stimulation of NBs has also been shown to enhance delivery and penetration of co-injected or loaded drugs in various preclinical tumor models 10 , 11 , 48 , 49 and for blood-brain-barrier disruption 7 , 8 , though intact NB extravasation was not validated and microscale events were not visualized. A plethora of ultrasound parameters have been used, typically with frequencies between 1-10 MHz, durations on the order of a few minutes, but greatly varying acoustic pressures from 100 kPa to several MPa.…”

Section: Resultsmentioning

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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Section: Resultsmentioning

confidence: 99%

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

et al. 2020

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“…Nanobubbles coupled with nanobodies targeting the prostate-specific membrane antigen (PSMA) facilitated prostate cancer imaging by ultrasonography [148]. Anti-G250 nanobody-bearing targeted nanobubbles improved ultrasound imaging of renal cell carcinomas in mouse models [149,150]. Anti-eGFP (cAbGFP4) and the clinically translatable anti-VCAM-1 (cAbVCAM1-5) nanobodies have been employed for tailoring microbubbles to improve their targeting and imaging potential both in vitro and in vivo [151,152].…”

Section: Discussion and Future Perspectivesmentioning

confidence: 99%

Transportation of Single-Domain Antibodies through the Blood–Brain Barrier

Ruiz-López

Schuhmacher

2021

Biomolecules

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Single-domain antibodies derive from the heavy-chain-only antibodies of Camelidae (camel, dromedary, llama, alpaca, vicuñas, and guananos; i.e., nanobodies) and cartilaginous fishes (i.e., VNARs). Their small size, antigen specificity, plasticity, and potential to recognize unique conformational epitopes represent a diagnostic and therapeutic opportunity for many central nervous system (CNS) pathologies. However, the blood–brain barrier (BBB) poses a challenge for their delivery into the brain parenchyma. Nevertheless, numerous neurological diseases and brain pathologies, including cancer, result in BBB leakiness favoring single-domain antibodies uptake into the CNS. Some single-domain antibodies have been reported to naturally cross the BBB. In addition, different strategies and methods to deliver both nanobodies and VNARs into the brain parenchyma can be exploited when the BBB is intact. These include device-based and physicochemical disruption of the BBB, receptor and adsorptive-mediated transcytosis, somatic gene transfer, and the use of carriers/shuttles such as cell-penetrating peptides, liposomes, extracellular vesicles, and nanoparticles. Approaches based on single-domain antibodies are reaching the clinic for other diseases. Several tailoring methods can be followed to favor the transport of nanobodies and VNARs to the CNS, avoiding the limitations imposed by the BBB to fulfill their therapeutic, diagnostic, and theragnostic promises for the benefit of patients suffering from CNS pathologies.

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“…18 Despite this prior work showing poor NB echogenicity, recent in vivo tumor CEUS imaging studies using NBs have concluded that NBs are echogenic. [19][20][21][22][23] We hypothesize that this discrepancy can be explained by MB contamination in the NB suspensions. Prior CEUS studies have demonstrated that total bubble volume fraction is a more accurate prediction of in vitro and in vivo echogenicity than number concentration.…”

Section: Introductionmentioning

confidence: 93%

Nanobubbles are Non-Echogenic for Fundamental-Mode Contrast-Enhanced Ultrasound Imaging

Myers

Navarro-Becerra

Borden

2022

Preprint

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Microbubbles (1–10 µm diameter) have been used as conventional ultrasound contrast agents (UCAs) for applications in contrast-enhanced ultrasound (CEUS) imaging. Nanobubbles (<1 µm diameter) have recently been proposed as potential extravascular UCAs that can extravasate from the leaky vasculature of tumors or sites of inflammation. However, the echogenicity of nanobubbles for CEUS remains controversial owing to prior studies that have shown very low ultrasound backscatter. We hypothesize that microbubble contamination in nanobubble formulations may explain the discrepancy. To test our hypothesis, we examined the size distributions of lipid-coated nanobubble and microbubble suspensions using multiple sizing techniques, examined their echogenicity in an agar phantom with fundamental-mode CEUS at 7 MHz and 330 kPa peak negative pressure, and interpreted our results with simulations of the modified Rayleigh-Plesset model. We found that nanobubble formulations contained a small contamination of microbubbles. Once the contribution from these microbubbles is removed from the acoustic backscatter, the acoustic contrast of the nanobubbles was shown to be near noise levels. This result indicates that nanobubbles have limited utility as UCAs for CEUS.

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<p>G250 Antigen-Targeting Drug-Loaded Nanobubbles Combined with Ultrasound Targeted Nanobubble Destruction: A Potential Novel Treatment for Renal Cell Carcinoma</p>

Cited by 27 publications

References 30 publications

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

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

Transportation of Single-Domain Antibodies through the Blood–Brain Barrier

Nanobubbles are Non-Echogenic for Fundamental-Mode Contrast-Enhanced Ultrasound Imaging

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