Specific Photothermal Ablation Of Ovarian Cancer By Carbon Nanotubes-mediated Near-infrared Light Irradiation

Objective:Multiwalled carbon nanotubes (MWCNTs) possess the characteristics of absorbingnear-nfrared(NIR) light and convert it into heat to kill the tumor cells with localthermal effects. Here we used CA125antigen as targets, specifically increased theaccumulation of MWCNTs in ovarian cancer cells, and then exposured tonear-infrared (NIR) radiation to kill ovarian cancer in vitro and in vivo.Methods:First, the CA125MAb covalently conjugated to MWCNTs to form CNTs-MAbcomplex by covalent method. Then the thermal effects of the therapy using CCK-8todetect cell viability ratios of ovarian cancer and osteosarcoma in vitro treated with thesame concentration of MAb, MWCNTs, CNTs-MAb after treated the cells by NIR(104nm,60J,300ms). Further, to detect the cell viability ratios of the two cancer cellstreated with different concentritions of CNTs-MAb (0、1/1024mg/ml、1/512mg/ml、1/256mg/ml、1/128mg/ml、1/64mg/ml、1/32mg/ml、1/16mg/ml、1/8mg/ml) underthe same NIR radiaton. The rate of cell apoptosis of ovarian cancer and osteosarcomacells was detected by Flow cytometry. Moreover we established mice bearingneoplasm (SKOV-3cell line and MG-63cell line) observed tumor growth and destruction in vivo with a injection in tumor site of MAb, MWCNTs and CNTs-MAb(200ul/mouse) followed by treatment with a near-infrared radiation (1064nm,60J，300ms).Results:The transmission electron microscope (TEM) showed CA125monoclonal antibodywas combined with MWCNTs.The immunofluorescence showed covalentCNTs-MAb specifically binded to the membrance of SKOV-3cells. Sameconcentrations of MWCNTs and CNTs-MAb separately treated SKOV-3cells afterNIR iiradiation. The cell viability of the two groups were statistically lower (P<0.05)compared with the control group. In contrast, there was no significant difference(P>0.05) in MG-63cells treated with same agents. After the NIR irradiation, the cellviability of SKOV-3and MG-63cells was decreased with the elevating of theconcentrations of CNTs-MAb. As the dose of CNTs-MAb increased, the rate of cellapoptosis of the SKOV-3and MG-63cells were significantly increased. Moreover,the rate of cell apoptosis of SKOV-3cells were higher than MG-63cells (P<0.05) atthe same treament. After NIR irradiation, the diameters of two kinds of tumors treatedwith MWCNTs both shrinked, but there were no difference between two kinds oftumors (P>0.05). Interestingly, the diameter of the ovarian cancer smaller than theosteosarcoma tumors treated with CNTs-MAb (P<0.05).Conclusions:1.CNTs-MAb could be used as specificly targeting thermal ablation ovariancancer cells with near-infrared radiation.2.In vivo and in vitro experiments suggested that the optimal concentrations ofCNTs-MAb targeting thermal ablation ovarian cancer was1/128mg/ml.