Cargando…
Nanodroplet-Mediated Histotripsy for Image-guided Targeted Ultrasound Cell Ablation
This paper is an initial work towards developing an image-guided, targeted ultrasound ablation technique by combining histotripsy with nanodroplets that can be selectively delivered to tumor cells. Using extremely short, high-pressure pulses, histotripsy generates a dense cloud of cavitating microbu...
Autores principales: | , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Ivyspring International Publisher
2013
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3841336/ https://www.ncbi.nlm.nih.gov/pubmed/24312155 http://dx.doi.org/10.7150/thno.6717 |
_version_ | 1782292769156366336 |
---|---|
author | Vlaisavljevich, Eli Durmaz, Yasemin Yuksel Maxwell, Adam ElSayed, Mohamed Xu, Zhen |
author_facet | Vlaisavljevich, Eli Durmaz, Yasemin Yuksel Maxwell, Adam ElSayed, Mohamed Xu, Zhen |
author_sort | Vlaisavljevich, Eli |
collection | PubMed |
description | This paper is an initial work towards developing an image-guided, targeted ultrasound ablation technique by combining histotripsy with nanodroplets that can be selectively delivered to tumor cells. Using extremely short, high-pressure pulses, histotripsy generates a dense cloud of cavitating microbubbles that fractionates tissue. We hypothesize that synthetic nanodroplets that encapsulate a perfluoropentane (PFP) core will transition upon exposure to ultrasound pulses into gas microbubbles, which will rapidly expand and collapse resulting in disruption of cells similar to the histotripsy process but at a significantly lower acoustic pressure. The significantly reduced cavitation threshold will allow histotripsy to be selectively delivered to the tumor tissue and greatly enhance the treatment efficiency while sparing neighboring healthy tissue. To test our hypothesis, we prepared nanodroplets with an average diameter of 204±4.7 nm at 37°C by self-assembly of an amphiphilic triblock copolymer around a PFP core followed by cross-linkage of the polymer shell forming stable nanodroplets. The nanodroplets were embedded in agarose tissue phantoms containing a sheet of red blood cells (RBCs), which were exposed to 2-cycle pulses applied by a 500 kHz focused transducer. Using a high speed camera to monitor microbubble generation, the peak negative pressure threshold needed to generate bubbles >50 μm in agarose phantoms containing nanodroplets was measured to be 10.8 MPa, which is significantly lower than the 28.8 MPa observed using ultrasound pulses alone. High speed images also showed cavitation microbubbles produced from the nanodroplets displayed expansion and collapse similar to histotripsy alone at higher pressures. Nanodroplet-mediated histotripsy created consistent, well-defined fractionation of the RBCs in agarose tissue phantoms at 10 Hz pulse repetition frequency similar to the lesions generated by histotripsy alone but at a significantly lower pressure. These results support our hypothesis and demonstrate the potential of using nanodroplet-mediated histotripsy for targeted cell ablation. |
format | Online Article Text |
id | pubmed-3841336 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Ivyspring International Publisher |
record_format | MEDLINE/PubMed |
spelling | pubmed-38413362013-12-05 Nanodroplet-Mediated Histotripsy for Image-guided Targeted Ultrasound Cell Ablation Vlaisavljevich, Eli Durmaz, Yasemin Yuksel Maxwell, Adam ElSayed, Mohamed Xu, Zhen Theranostics Research Paper This paper is an initial work towards developing an image-guided, targeted ultrasound ablation technique by combining histotripsy with nanodroplets that can be selectively delivered to tumor cells. Using extremely short, high-pressure pulses, histotripsy generates a dense cloud of cavitating microbubbles that fractionates tissue. We hypothesize that synthetic nanodroplets that encapsulate a perfluoropentane (PFP) core will transition upon exposure to ultrasound pulses into gas microbubbles, which will rapidly expand and collapse resulting in disruption of cells similar to the histotripsy process but at a significantly lower acoustic pressure. The significantly reduced cavitation threshold will allow histotripsy to be selectively delivered to the tumor tissue and greatly enhance the treatment efficiency while sparing neighboring healthy tissue. To test our hypothesis, we prepared nanodroplets with an average diameter of 204±4.7 nm at 37°C by self-assembly of an amphiphilic triblock copolymer around a PFP core followed by cross-linkage of the polymer shell forming stable nanodroplets. The nanodroplets were embedded in agarose tissue phantoms containing a sheet of red blood cells (RBCs), which were exposed to 2-cycle pulses applied by a 500 kHz focused transducer. Using a high speed camera to monitor microbubble generation, the peak negative pressure threshold needed to generate bubbles >50 μm in agarose phantoms containing nanodroplets was measured to be 10.8 MPa, which is significantly lower than the 28.8 MPa observed using ultrasound pulses alone. High speed images also showed cavitation microbubbles produced from the nanodroplets displayed expansion and collapse similar to histotripsy alone at higher pressures. Nanodroplet-mediated histotripsy created consistent, well-defined fractionation of the RBCs in agarose tissue phantoms at 10 Hz pulse repetition frequency similar to the lesions generated by histotripsy alone but at a significantly lower pressure. These results support our hypothesis and demonstrate the potential of using nanodroplet-mediated histotripsy for targeted cell ablation. Ivyspring International Publisher 2013-10-20 /pmc/articles/PMC3841336/ /pubmed/24312155 http://dx.doi.org/10.7150/thno.6717 Text en © Ivyspring International Publisher. This is an open-access article distributed under the terms of the Creative Commons License (http://creativecommons.org/licenses/by-nc-nd/3.0/). Reproduction is permitted for personal, noncommercial use, provided that the article is in whole, unmodified, and properly cited. |
spellingShingle | Research Paper Vlaisavljevich, Eli Durmaz, Yasemin Yuksel Maxwell, Adam ElSayed, Mohamed Xu, Zhen Nanodroplet-Mediated Histotripsy for Image-guided Targeted Ultrasound Cell Ablation |
title | Nanodroplet-Mediated Histotripsy for Image-guided Targeted Ultrasound Cell Ablation |
title_full | Nanodroplet-Mediated Histotripsy for Image-guided Targeted Ultrasound Cell Ablation |
title_fullStr | Nanodroplet-Mediated Histotripsy for Image-guided Targeted Ultrasound Cell Ablation |
title_full_unstemmed | Nanodroplet-Mediated Histotripsy for Image-guided Targeted Ultrasound Cell Ablation |
title_short | Nanodroplet-Mediated Histotripsy for Image-guided Targeted Ultrasound Cell Ablation |
title_sort | nanodroplet-mediated histotripsy for image-guided targeted ultrasound cell ablation |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3841336/ https://www.ncbi.nlm.nih.gov/pubmed/24312155 http://dx.doi.org/10.7150/thno.6717 |
work_keys_str_mv | AT vlaisavljevicheli nanodropletmediatedhistotripsyforimageguidedtargetedultrasoundcellablation AT durmazyaseminyuksel nanodropletmediatedhistotripsyforimageguidedtargetedultrasoundcellablation AT maxwelladam nanodropletmediatedhistotripsyforimageguidedtargetedultrasoundcellablation AT elsayedmohamed nanodropletmediatedhistotripsyforimageguidedtargetedultrasoundcellablation AT xuzhen nanodropletmediatedhistotripsyforimageguidedtargetedultrasoundcellablation |