Characterising the chemical and physical properties of phase-change nanodroplets

Weiqi Zhang; Hilde Metzger; Stavros Vlatakis; Amelia Claxton; Maria Carbajal; Leong Fan Fung; James Mason; Andrew Chan; Antonios Pouliopoulos; Roland Fleck; Paul Prentice; Maya Thanou

doi:10.1016/j.ultsonch.2023.106445

Characterising the chemical and physical properties of phase-change nanodroplets

Weiqi Zhang, Hilde Metzger, Stavros Vlatakis, Amelia Claxton, Maria Carbajal, Leong Fan Fung, James Mason, Andrew Chan, Antonios Pouliopoulos, Roland Fleck, Paul Prentice, Maya Thanou^*

^*Corresponding author for this work

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Abstract

Phase-change nanodroplets have attracted increasing interest in recent years as ultrasound theranostic nanoparticles. They are smaller compared to microbubbles and they may distribute better in tissues (e.g. in tumours). They are composed of a stabilising shell and a perfluorocarbon core. Nanodroplets can vaporise into echogenic microbubbles forming cavitation nuclei when exposed to ultrasound. Their perfluorocarbon core phase-change is responsible for the acoustic droplet vaporisation. However, methods to quantify the perfluorocarbon core in nanodroplets are lacking. This is an important feature that can help explain nanodroplet phase change characteristics. In this study, we fabricated nanodroplets using lipids shell and perfluorocarbons. To assess the amount of perfluorocarbon in the core we used two methods, 19F NMR and FTIR. To assess the cavitation after vaporisation we used an ultrasound transducer (1.1 MHz) and a high-speed camera. The 19F NMR based method showed that the fluorine signal correlated accurately with the perfluorocarbon concentration. Using this correlation, we were able to quantify the perfluorocarbon core of nanodroplets. This method was used to assess the content of the perfluorocarbon of the nanodroplets in solutions over time. It was found that perfluoropentane nanodroplets lost their content faster and at higher ratio compared to perfluorohexane nanodroplets. The high-speed imaging indicates that the nanodroplets generate cavitation comparable to that from commercial contrast agent microbubbles. Nanodroplet characterisation should include perfluorocarbon concentration assessment as critical information for their development.

Original language	English
Article number	106445
Journal	Ultrasonics Sonochemistry
Volume	97
DOIs	https://doi.org/10.1016/j.ultsonch.2023.106445
Publication status	Published - 31 May 2023

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10.1016/j.ultsonch.2023.106445Licence: CC BY-NC-ND

1-s2.0-S1350417723001578-mainFinal published version, 4.03 MBLicence: CC BY-NC-ND

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@article{352804c805ca4516b2f5ba7f1213e4db,

title = "Characterising the chemical and physical properties of phase-change nanodroplets",

abstract = "Phase-change nanodroplets have attracted increasing interest in recent years as ultrasound theranostic nanoparticles. They are smaller compared to microbubbles and they may distribute better in tissues (e.g. in tumours). They are composed of a stabilising shell and a perfluorocarbon core. Nanodroplets can vaporise into echogenic microbubbles forming cavitation nuclei when exposed to ultrasound. Their perfluorocarbon core phase-change is responsible for the acoustic droplet vaporisation. However, methods to quantify the perfluorocarbon core in nanodroplets are lacking. This is an important feature that can help explain nanodroplet phase change characteristics. In this study, we fabricated nanodroplets using lipids shell and perfluorocarbons. To assess the amount of perfluorocarbon in the core we used two methods, 19F NMR and FTIR. To assess the cavitation after vaporisation we used an ultrasound transducer (1.1 MHz) and a high-speed camera. The 19F NMR based method showed that the fluorine signal correlated accurately with the perfluorocarbon concentration. Using this correlation, we were able to quantify the perfluorocarbon core of nanodroplets. This method was used to assess the content of the perfluorocarbon of the nanodroplets in solutions over time. It was found that perfluoropentane nanodroplets lost their content faster and at higher ratio compared to perfluorohexane nanodroplets. The high-speed imaging indicates that the nanodroplets generate cavitation comparable to that from commercial contrast agent microbubbles. Nanodroplet characterisation should include perfluorocarbon concentration assessment as critical information for their development.",

author = "Weiqi Zhang and Hilde Metzger and Stavros Vlatakis and Amelia Claxton and Maria Carbajal and Fung, {Leong Fan} and James Mason and Andrew Chan and Antonios Pouliopoulos and Roland Fleck and Paul Prentice and Maya Thanou",

note = "Funding Information: The authors would like to thank financial support of the following organisations: Weiqi Zhang acknowledges the support from the King's-China Scholarship Council PhD Scholarship Programme (201909150005), Stavros Vlatakis acknowledges support by UKRI BBSRC London Interdisciplinary Doctoral Programme BB/T008709/1, Amelia Claxton acknowledges the support by the City of London Cancer Research UK, and Hilde Metzger is supported by the UKRI EPSRC Future Ultrasonic Engineering (EP/S023879/1). The authors are thankful for Dr Paul Cressey, Owen Harrison, Shazwan Abd Shukor and Xiang Luo offering help with revising the paper, Dr Ian Rivens and Dr Petros Mouratidis at the Institute of Cancer Research (ICR) for their guidance on acoustic properties of NDs. NMR spectra were recorded in the Centre for Biomolecular Spectroscopy at King's College London, which was funded by the Welcome Trust and British Heart Foundation (ref. 202767/Z/16/Z and IG/16/2/32273). We would like to thank Dr James Jarvis help recording the spectra. The authors would like to dedicate this work in the memory of Dr Michael Wright who passed away in 15-09-2022. Funding Information: The authors would like to thank financial support of the following organisations: Weiqi Zhang acknowledges the support from the King{\textquoteright}s-China Scholarship Council PhD Scholarship Programme (201909150005), Stavros Vlatakis acknowledges support by UKRI BBSRC London Interdisciplinary Doctoral Programme BB/T008709/1, Amelia Claxton acknowledges the support by the City of London Cancer Research UK, and Hilde Metzger is supported by the UKRI EPSRC Future Ultrasonic Engineering (EP/S023879/1). The authors are thankful for Dr Paul Cressey, Owen Harrison, Shazwan Abd Shukor and Xiang Luo offering help with revising the paper, Dr Ian Rivens and Dr Petros Mouratidis at the Institute of Cancer Research (ICR) for their guidance on acoustic properties of NDs. NMR spectra were recorded in the Centre for Biomolecular Spectroscopy at King{\textquoteright}s College London, which was funded by the Welcome Trust and British Heart Foundation (ref. 202767/Z/16/Z and IG/16/2/32273). We would like to thank Dr James Jarvis help recording the spectra. Publisher Copyright: {\textcopyright} 2023",

year = "2023",

month = may,

day = "31",

doi = "10.1016/j.ultsonch.2023.106445",

language = "English",

volume = "97",

journal = "Ultrasonics Sonochemistry",

issn = "1350-4177",

publisher = "Elsevier",

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T1 - Characterising the chemical and physical properties of phase-change nanodroplets

AU - Zhang, Weiqi

AU - Metzger, Hilde

AU - Vlatakis, Stavros

AU - Claxton, Amelia

AU - Carbajal, Maria

AU - Fung, Leong Fan

AU - Mason, James

AU - Chan, Andrew

AU - Pouliopoulos, Antonios

AU - Fleck, Roland

AU - Prentice, Paul

AU - Thanou, Maya

N1 - Funding Information: The authors would like to thank financial support of the following organisations: Weiqi Zhang acknowledges the support from the King's-China Scholarship Council PhD Scholarship Programme (201909150005), Stavros Vlatakis acknowledges support by UKRI BBSRC London Interdisciplinary Doctoral Programme BB/T008709/1, Amelia Claxton acknowledges the support by the City of London Cancer Research UK, and Hilde Metzger is supported by the UKRI EPSRC Future Ultrasonic Engineering (EP/S023879/1). The authors are thankful for Dr Paul Cressey, Owen Harrison, Shazwan Abd Shukor and Xiang Luo offering help with revising the paper, Dr Ian Rivens and Dr Petros Mouratidis at the Institute of Cancer Research (ICR) for their guidance on acoustic properties of NDs. NMR spectra were recorded in the Centre for Biomolecular Spectroscopy at King's College London, which was funded by the Welcome Trust and British Heart Foundation (ref. 202767/Z/16/Z and IG/16/2/32273). We would like to thank Dr James Jarvis help recording the spectra. The authors would like to dedicate this work in the memory of Dr Michael Wright who passed away in 15-09-2022. Funding Information: The authors would like to thank financial support of the following organisations: Weiqi Zhang acknowledges the support from the King’s-China Scholarship Council PhD Scholarship Programme (201909150005), Stavros Vlatakis acknowledges support by UKRI BBSRC London Interdisciplinary Doctoral Programme BB/T008709/1, Amelia Claxton acknowledges the support by the City of London Cancer Research UK, and Hilde Metzger is supported by the UKRI EPSRC Future Ultrasonic Engineering (EP/S023879/1). The authors are thankful for Dr Paul Cressey, Owen Harrison, Shazwan Abd Shukor and Xiang Luo offering help with revising the paper, Dr Ian Rivens and Dr Petros Mouratidis at the Institute of Cancer Research (ICR) for their guidance on acoustic properties of NDs. NMR spectra were recorded in the Centre for Biomolecular Spectroscopy at King’s College London, which was funded by the Welcome Trust and British Heart Foundation (ref. 202767/Z/16/Z and IG/16/2/32273). We would like to thank Dr James Jarvis help recording the spectra. Publisher Copyright: © 2023

PY - 2023/5/31

Y1 - 2023/5/31

N2 - Phase-change nanodroplets have attracted increasing interest in recent years as ultrasound theranostic nanoparticles. They are smaller compared to microbubbles and they may distribute better in tissues (e.g. in tumours). They are composed of a stabilising shell and a perfluorocarbon core. Nanodroplets can vaporise into echogenic microbubbles forming cavitation nuclei when exposed to ultrasound. Their perfluorocarbon core phase-change is responsible for the acoustic droplet vaporisation. However, methods to quantify the perfluorocarbon core in nanodroplets are lacking. This is an important feature that can help explain nanodroplet phase change characteristics. In this study, we fabricated nanodroplets using lipids shell and perfluorocarbons. To assess the amount of perfluorocarbon in the core we used two methods, 19F NMR and FTIR. To assess the cavitation after vaporisation we used an ultrasound transducer (1.1 MHz) and a high-speed camera. The 19F NMR based method showed that the fluorine signal correlated accurately with the perfluorocarbon concentration. Using this correlation, we were able to quantify the perfluorocarbon core of nanodroplets. This method was used to assess the content of the perfluorocarbon of the nanodroplets in solutions over time. It was found that perfluoropentane nanodroplets lost their content faster and at higher ratio compared to perfluorohexane nanodroplets. The high-speed imaging indicates that the nanodroplets generate cavitation comparable to that from commercial contrast agent microbubbles. Nanodroplet characterisation should include perfluorocarbon concentration assessment as critical information for their development.

AB - Phase-change nanodroplets have attracted increasing interest in recent years as ultrasound theranostic nanoparticles. They are smaller compared to microbubbles and they may distribute better in tissues (e.g. in tumours). They are composed of a stabilising shell and a perfluorocarbon core. Nanodroplets can vaporise into echogenic microbubbles forming cavitation nuclei when exposed to ultrasound. Their perfluorocarbon core phase-change is responsible for the acoustic droplet vaporisation. However, methods to quantify the perfluorocarbon core in nanodroplets are lacking. This is an important feature that can help explain nanodroplet phase change characteristics. In this study, we fabricated nanodroplets using lipids shell and perfluorocarbons. To assess the amount of perfluorocarbon in the core we used two methods, 19F NMR and FTIR. To assess the cavitation after vaporisation we used an ultrasound transducer (1.1 MHz) and a high-speed camera. The 19F NMR based method showed that the fluorine signal correlated accurately with the perfluorocarbon concentration. Using this correlation, we were able to quantify the perfluorocarbon core of nanodroplets. This method was used to assess the content of the perfluorocarbon of the nanodroplets in solutions over time. It was found that perfluoropentane nanodroplets lost their content faster and at higher ratio compared to perfluorohexane nanodroplets. The high-speed imaging indicates that the nanodroplets generate cavitation comparable to that from commercial contrast agent microbubbles. Nanodroplet characterisation should include perfluorocarbon concentration assessment as critical information for their development.

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U2 - 10.1016/j.ultsonch.2023.106445

DO - 10.1016/j.ultsonch.2023.106445

M3 - Article

SN - 1350-4177

VL - 97

JO - Ultrasonics Sonochemistry

JF - Ultrasonics Sonochemistry

M1 - 106445

ER -

Characterising the chemical and physical properties of phase-change nanodroplets

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