Enhanced radiosensitization for cancer treatment with gold nanoparticles through sonoporation
Journal
International Journal of Molecular Sciences
Journal Volume
21
Journal Issue
21
Pages
1-16
Date Issued
2020
Author(s)
Abstract
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. ? 2020, MDPI AG. All rights reserved.
SDGs
Other Subjects
gold nanoparticle; macrogol; vasculotropin receptor 2; gold; H2AX protein, human; histone; KDR protein, human; metal nanoparticle; vasculotropin receptor 2; animal experiment; animal model; apoptosis; aqueous solution; Article; cancer radiotherapy; cancer recurrence; cancer survival; cancer therapy; clonogenic assay; colony formation; controlled study; DNA damage; double stranded DNA break; genetic marker; Huh-7 cell line; human; human cell; immunofluorescence; in vitro study; in vivo study; inductively coupled plasma mass spectrometry; liver cell carcinoma; male; mass spectrometry; microbubble; mouse; nonhuman; optical density; phase contrast microscopy; radiosensitization; reticuloendothelial system; spectrophotometry; transmission electron microscopy; tumor volume; tumor xenograft; X irradiation; animal; cell survival; devices; drug delivery system; drug screening; liver cell carcinoma; liver tumor; metabolism; microbubble; pathology; procedures; radiation response; radiation tolerance; tumor cell line; ultrasound; Animals; Carcinoma, Hepatocellular; Cell Line, Tumor; Cell Survival; DNA Damage; Drug Delivery Systems; Gold; Histones; Humans; Liver Neoplasms; Metal Nanoparticles; Mice; Microbubbles; Radiation Tolerance; Sonication; Vascular Endothelial Growth Factor Receptor-2; Xenograft Model Antitumor Assays
Publisher
MDPI AG
Type
journal article