Title:Using a Hybrid Radioenhancer to Discover Tumor Cell-targeted Treatment for Osteosarcoma: An In Vitro Study
Volume: 28
Issue: 19
Author(s): Fu-I Tung, Li-Chin Chen, Yu-Chi Wang, Ming-Hong Chen, Pei-Wei Shueng and Tse-Ying Liu*
Affiliation:
- Department of Biomedical Engineering, National Yang-Ming University, Taipei, Taiwan,China
Keywords:
Radiotherapy, low-dose radiation, carboxymethyl-hexanoyl chitosan, gold, iron oxide, 5-aminolevulinic
acid.
Abstract: Osteosarcoma is insensitive to radiation. High-dose radiation is often used as a
treatment but causes side effects in patients. Hence, it is important to develop tumor cell--
targeted radiotherapy that could improve radiotherapy efficiency on tumor cells and reduce
the toxic effect on normal cells during radiation treatment. In this study, we developed
an innovative method for treating osteosarcoma by using a novel radiation-enhancer
(i.e., carboxymethyl-hexanoyl chitosan-coated self-assembled Au@Fe3O4 nanoparticles;
CSAF NPs). CSAF NPs were employed together with 5-aminolevulinic acid (5-
ALA) to achieve tumor cell-targeted radiotherapy. In this study, osteosarcoma cells
(MG63) and normal cells (MC3T3-E1) were used for an in vitro investigation, in which
reactive oxygen species (ROS) assay, cell viability assay, clonogenic assay, and western
blot were used to confirm the treatment efficiency. The ROS assay showed that the combination
of CSAF NPs and 5-ALA enhanced radiation-induced ROS production in tumor
cells (MG63); however, this was not observed in normal cells (MC3T3-E1). The cell viability
ratio of normal cells to tumor cells after treatment with CSAF NPs and 5-ALA
reached 2.79. Moreover, the clonogenic assay showed that the radiosensitivity of MG63
cells was increased by the combination use of CSAF NPs and 5-ALA. This was supported
by performing a western blot that confirmed the expression of cytochrome c (a marker
of cell mitochondria damage) and caspase-3 (a marker of cell apoptosis). The results provide
an essential basis for developing tumor-cell targeted radiotherapy by means of low--
dose radiation.
