Enhanced Radiosensitization for Cancer Treatment with Gold Nanoparticles through Sonoporation

• Main Authors: Shao-Lun Lu, Wei-Wen Liu, Jason Chia-Hsien Cheng, Lien-Chieh Lin, Churng-Ren Chris Wang, Pai-Chi Li
• Format: Article
• Language: English
• Published: MDPI AG 2020-11-01
• Series: International Journal of Molecular Sciences
• Subjects: sonoporation; microbubbles; gold nanoparticles; cavitation; radiotherapy; radiosensitization
• Online Access: https://www.mdpi.com/1422-0067/21/21/8370

<b> </b>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.