Enhanced Radiosensitization for Cancer Treatment with Gold Nanoparticles through Sonoporation.
Shao-Lun LuWei-Wen LiuJason Chia-Hsien ChengLien-Chieh LinChurng-Ren Chris WangPai-Chi LiPublished in: International journal of molecular sciences (2020)
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.
Keyphrases
- gold nanoparticles
- vascular endothelial growth factor
- endothelial cells
- dna damage
- mouse model
- oxidative stress
- radiation induced
- reduced graphene oxide
- early stage
- magnetic resonance imaging
- high resolution
- endoplasmic reticulum stress
- high throughput
- cell death
- cell therapy
- radiation therapy
- computed tomography
- dna repair
- mass spectrometry
- stem cells
- locally advanced
- mesenchymal stem cells
- cell cycle arrest
- bone marrow
- reactive oxygen species
- contrast enhanced