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Figure 7. The morphologies of C6 cells. Upper row: control group (center), proton exposed group (left), PTX treated group (right). Lower row: proton exposure with sequential treatement of PTX group (left), TCPT treatment group (right). Proton exposure for the treatment was 8 Gy. Scale bar = 86.77 μm.

Figure 8. The results of colonogenic assays of C6 cells with different radiation doses and different treatment with PTX, D-SPIONs, FA-D-SPIONs, or FA-PTX-DSPIONs. The measured data are fitted to LQ model.

Figure 9. The results of Annexin V assays: left graphs show flow-cytometry analysis with Annexin V on proton beam irradiated C6 cells (SG1, SG3 and SG5) and without irradiation (CG). Right graph represents cell apoptosis of each group (Annexin V). The data present as the mean ± SD (n¼3). *p<0.05.

Figure 10. The results of capase 3/7 assays: left graphs show flow-cytometry analysis with caspase 3/7 on proton beam-irradiated C6 cells (SG1, SG3 and SG5) and without irradiation (CG). Right graph represents cell apoptosis of each group (caspase 3/7). The data present as the mean ± SD (n¼3). *p<0.05.

Abstract
PURPOSE:
This report presents novel nanoparticle-based drug delivery system (NPDDS) aiming to targeting chemo-proton therapy (TCPT) to improve the therapeutic efficacy on brain cancer treatments.

MATERIALS AND METHODS:
A NPDDS, superparamagnetic iron oxide nanoparticles conjugated with folate and paclitaxel, was synthesized and applied to C6 brain cancer cell line that was prepared for targeting chemo-proton therapy. The characterization of NPDDS was analyzed by transmission electron microscope (TEM) and Fourier transform infrared (FTIR) spectroscopy. The uptake of NPDDS into the cytoplasm of C6 cells was observed by confocal laser scanning microscopy (CLSM). The therapeutic efficacy of proton beam was quantitatively evaluated by flow cytometry and clonogenic assay at various radiation dose.

RESULTS:
NPDDS was synthesized in the uniform size distribution with a mean diameter of 5.44 ± 0.70 nm, and it showed no significant cytotoxicity at the concentration lower than 200 ng/mL. Radiosensitization enhancement factors of PTX, D-SPIONs and FA-PTX-D-SPIONs were 1.35, 1.16 and 1.52, respectively.

CONCLUSIONS:
It was demonstrated that TCPT improved the therapeutic efficacy of the proton beam therapy when the synthesized novel NPDDS was administrated. The improvement in therapeutic efficacy was achieved by the synergetic effect of drug delivery increased by FA, radiosensitivity increased by PTX and absorption of proton energy increased by SPIONs.

Author information

Kang SH1, Hong SP1, Kang BS1.
1
a Department of Radiological Science , Konyang University , Daejeon , South Korea.