TY - JOUR
T1 - Stable Encapsulation of Air in Mesoporous Silica Nanoparticles
T2 - Fluorocarbon-Free Nanoscale Ultrasound Contrast Agents
AU - Yildirim, Adem
AU - Chattaraj, Rajarshi
AU - Blum, Nicholas T.
AU - Goldscheitter, Galen M.
AU - Goodwin, Andrew P.
N1 - Funding Information:
This work was supported by NIH (Grant Nos. DP2EB020401, R21EB018034, and R00CA153935). The authors thank Dr. Omer Yehezkeli and Prof. Jennifer Cha for helpful discussions. The authors would also like to thank Prof. Amy Palmer for use of her Tecan Safire2 plate reader, Prof. Jeffrey Stansbury for use of his Thermo Scientific Nicolet 6700 FTIR and Perkin Elmer Pyris 1 TGA, Prof. J. Will Medlin for use of his Micromeritics Chemisorb 2720, Dr. Parag Shah for his help with the TGA and FTIR measurements and Lucas Ellis for his help with the surface area measurements.
Publisher Copyright:
© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
PY - 2016/6/8
Y1 - 2016/6/8
N2 - While gas-filled micrometer-sized ultrasound contrast agents vastly improve signal-to-noise ratios, microbubbles have short circulation lifetimes and poor extravasation from the blood. Previously reported fluorocarbon-based nanoscale contrast agents are more stable but their contrast is generally lower owing to their size and dispersity. The contrast agents reported here are composed of silica nanoparticles of ≈100 nm diameter that are filled with ≈3 nm columnar mesopores. Functionalization of the silica surface with octyl groups and resuspension with Pluronic F127 create particles with pores that remain filled with air but are stable in buffer and serum. Administration of high intensity focused ultrasound (HIFU) allows sensitive imaging of the silica nanoparticles down to 1010 particles mL−1 , with continuous imaging for at least 20 min. Control experiments with different silica particles supported the hypothesis that entrapped air could be pulled into bubble nuclei, which can then in turn act as acoustic scatterers. This process results in very little hemolysis in whole blood, indicating potential for nontoxic blood pool imaging. Finally, the particles are lyophilized and reconstituted or stored in PBS (phosphate-buffered saline, at least for four months) with no loss in contrast, indicating stability to storage and reformulation.
AB - While gas-filled micrometer-sized ultrasound contrast agents vastly improve signal-to-noise ratios, microbubbles have short circulation lifetimes and poor extravasation from the blood. Previously reported fluorocarbon-based nanoscale contrast agents are more stable but their contrast is generally lower owing to their size and dispersity. The contrast agents reported here are composed of silica nanoparticles of ≈100 nm diameter that are filled with ≈3 nm columnar mesopores. Functionalization of the silica surface with octyl groups and resuspension with Pluronic F127 create particles with pores that remain filled with air but are stable in buffer and serum. Administration of high intensity focused ultrasound (HIFU) allows sensitive imaging of the silica nanoparticles down to 1010 particles mL−1 , with continuous imaging for at least 20 min. Control experiments with different silica particles supported the hypothesis that entrapped air could be pulled into bubble nuclei, which can then in turn act as acoustic scatterers. This process results in very little hemolysis in whole blood, indicating potential for nontoxic blood pool imaging. Finally, the particles are lyophilized and reconstituted or stored in PBS (phosphate-buffered saline, at least for four months) with no loss in contrast, indicating stability to storage and reformulation.
KW - aur encapsulation
KW - biomedical applications
KW - imaging
KW - mesoporous silica
KW - surface science
KW - ultrasound contrast agents
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U2 - 10.1002/adhm.201600030
DO - 10.1002/adhm.201600030
M3 - Article
C2 - 26990167
AN - SCOPUS:84976597910
VL - 5
SP - 1290
EP - 1298
JO - Advanced healthcare materials
JF - Advanced healthcare materials
SN - 2192-2640
IS - 11
ER -