Enhanced Radiosensitization for Cancer Treatment with Gold Nanoparticles through Sonoporation

We demonstrate the megavoltage (MV) radiosensitization of a human liver cancer line by combining gold-nanoparticle-encapsulated microbubbles (AuMBs) with ultrasound. Microbubbles-mediated sonoporation was administered for 5 min, at 2 h prior to applying radiotherapy. The intracellular concentration...

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Bibliographic Details
Published in:	International journal of molecular sciences 2020-11, Vol.21 (21), p.8370
Main Authors:	Lu, Shao-Lun, Liu, Wei-Wen, Cheng, Jason Chia-Hsien, Lin, Lien-Chieh, Wang, Churng-Ren Chris, Li, Pai-Chi
Format:	Article
Language:	eng
Subjects:	Animals Carcinoma, Hepatocellular - metabolism Carcinoma, Hepatocellular - pathology Carcinoma, Hepatocellular - therapy cavitation Cell Line, Tumor Cell Survival - radiation effects DNA Damage Drug Delivery Systems Gold - administration & dosage gold nanoparticles Histones - metabolism Humans Liver Neoplasms - metabolism Liver Neoplasms - pathology Liver Neoplasms - therapy Metal Nanoparticles - administration & dosage Mice Microbubbles Radiation Tolerance radiosensitization radiotherapy Sonication - instrumentation Sonication - methods sonoporation Vascular Endothelial Growth Factor Receptor-2 - antagonists & inhibitors Xenograft Model Antitumor Assays
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Summary:	We demonstrate the megavoltage (MV) radiosensitization of a human liver cancer line by combining gold-nanoparticle-encapsulated microbubbles (AuMBs) with ultrasound. Microbubbles-mediated sonoporation was administered for 5 min, at 2 h prior to applying radiotherapy. The intracellular concentration of gold nanoparticles (AuNPs) increased with the inertial cavitation of AuMBs in a dose-dependent manner. A higher inertial cavitation dose was also associated with more DNA damage, higher levels of apoptosis markers, and inferior cell surviving fractions after MV X-ray irradiation. The dose-modifying ratio in a clonogenic assay was 1.56 ± 0.45 for a 10% surviving fraction. In a xenograft mouse model, combining vascular endothelial growth factor receptor 2 (VEGFR2)-targeted AuMBs with sonoporation significantly delayed tumor regrowth. A strategy involving the spatially and temporally controlled release of AuNPs followed by clinically utilized MV irradiation shows promising results that make it worthy of further translational investigations.
ISSN:	1422-0067 1661-6596 1422-0067