TY - JOUR
T1 - Protein-Coated Biodegradable Gas-Stabilizing Nanoparticles for Cancer Therapy and Diagnosis Using Focused Ultrasound
AU - Sabuncu, Sinan
AU - Montoya Mira, Jose
AU - Quentel, Arnaud
AU - Gomes, Michelle M.
AU - Civitci, Fehmi
AU - Fischer, Jared M.
AU - Yildirim, Adem
N1 - Publisher Copyright:
© 2022 Wiley-VCH GmbH.
PY - 2023/1/17
Y1 - 2023/1/17
N2 - Surface-engineered hydrophobic nanoparticles that can stabilize small gas pockets on their surfaces (i.e., gas-stabilizing nanoparticles, GSNs) have been recently shown to be excellent contrast and cavitation agents for ultrasound theranostics. However, previously developed GSNs are not biodegradable, which limits their clinical translation potential. Here the development of biodegradable GSNs is shown by coating hydrophobically modified mesoporous silica nanoparticles with different protein solutions. It is found that these novel GSNs retain strong cavitation activity while rapidly degrading in simulated body fluid (SBF) or in vivo in days or a few weeks, respectively. Interestingly, GSNs coated with other stabilizing layers, Pluronic F127 polymer or phospholipids, demonstrated significantly slower degradation rates with only partial degradation even after a month of incubation in SBF. Next, it is shown that these biodegradable GSNs can be used to ablate tumor xenografts at lower ultrasound intensities, thus avoiding the side effects of high-intensity ultrasound. Finally, it is shown that only tumors treated with GSNs and ultrasound can specifically enrich for circulating tumor DNA, which will improve liquid biopsies for understanding tumor heterogeneity and treatment response. Overall, this study details a simple yet effective method for preparing biodegradable GSNs with broad potential for applications in cancer diagnosis and therapy.
AB - Surface-engineered hydrophobic nanoparticles that can stabilize small gas pockets on their surfaces (i.e., gas-stabilizing nanoparticles, GSNs) have been recently shown to be excellent contrast and cavitation agents for ultrasound theranostics. However, previously developed GSNs are not biodegradable, which limits their clinical translation potential. Here the development of biodegradable GSNs is shown by coating hydrophobically modified mesoporous silica nanoparticles with different protein solutions. It is found that these novel GSNs retain strong cavitation activity while rapidly degrading in simulated body fluid (SBF) or in vivo in days or a few weeks, respectively. Interestingly, GSNs coated with other stabilizing layers, Pluronic F127 polymer or phospholipids, demonstrated significantly slower degradation rates with only partial degradation even after a month of incubation in SBF. Next, it is shown that these biodegradable GSNs can be used to ablate tumor xenografts at lower ultrasound intensities, thus avoiding the side effects of high-intensity ultrasound. Finally, it is shown that only tumors treated with GSNs and ultrasound can specifically enrich for circulating tumor DNA, which will improve liquid biopsies for understanding tumor heterogeneity and treatment response. Overall, this study details a simple yet effective method for preparing biodegradable GSNs with broad potential for applications in cancer diagnosis and therapy.
KW - biodegradable nanoparticles
KW - focused ultrasound
KW - hydrophobic surface modification
KW - liquid biopsy
KW - mesoporous silica nanoparticles
KW - tumor ablation
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U2 - 10.1002/admi.202201543
DO - 10.1002/admi.202201543
M3 - Article
AN - SCOPUS:85142779433
SN - 2196-7350
VL - 10
JO - Advanced Materials Interfaces
JF - Advanced Materials Interfaces
IS - 2
M1 - 2201543
ER -