Tumor growth curve

To analyze the therapeutic effect of the PSS-AuNRs on photothermal ablation of solid tumors, the tumor (EMT-6 cells, 1*10⁶ cells in 30 µl PBS) was induced by intratumoral injection on the ear of female mice (Balb/c). When the tumor size grew to approximately 3 mm in diameter, PSS-Au NRs (~10 µg) were directly injected into mice’s ears. After 22~24 h, the mouse was anesthetized with ether, and then the tumor region was irradiated

with a laser for 2 minutes. In order to ensure the photothermolysis was the only factor that destroyed the solid tumors, setting relative control groups was necessary. There are three control groups: (i) tumors only, as shown in Fig. 3.12; (ii) tumors with exposure by 808 nm laser, 0.6 W/cm², for 120 s, as shown in Fig. 3.13; (iii) tumors with PSS-AuNRs by intratumoral injection as shown in Fig. 3.14;

and there is one experimental group with PSS-AuNRs and exposed under power density 0.6 W/cm² for 120 s, as shown in Fig. 3.15

Fig. 3.12 Control group (tumors only). (a)~(f) are before induced tumors, and after induced for 5 days, 8 days, 11 days, 15 days, 20 days, respectively.

Fig. 3.13 Control group (tumors exposed by laser). (a)~(f) are before induced tumors, and after induced for 5 days, 8 days, 11 days, 15 days, 20 days, respectively. Exposure with laser on the 12^nd day, power density is 0.6 W/cm², for 120 s. From this result, it can be observed that the laser was excluded as a factor, which destroys the solid tumors.

Fig. 3.14 Control group (tumors with PSS-AuNRs), Fig. (a)~(f) are after induced for 5 days, 8 days, 11 days, 15 days, 20 days, 24 days, respectively. 10 µg PSS-AuNRs were intratumorally injected into the solid tumor on the 11^st day. From this result, it can be observed that the PSS-AuNRs was excluded as a cytotoxic factor.

Fig. 3.15 Experimental group, the tumors were exposed with laser on the 12^nd day, power density is 0.6 W/cm², for 120 seconds.

(a)~(g) are after induced for 5 days, 8 days, 11 days, 15 days, 20 days, 24 days, 28 days, respectively.

After calculation for the tumors size, the growth curve was presented in Fig. 3.16.

Fig. 3.16 Growth Curve.

The green-colored, blue-colored, black-colored and the red-colored symbol mean growth curve of tumors, tumors with laser, tumors with AuNRs and tumors with AuNRs under exposed by laser, respectively.

3.3.2 Histological study

Histological sections of tumor tissues from each group confirmed the successful destruction of tumor cells by the photothermal effect by PSS-AuNRs. Fig. 3.16 (a)~(f) show the results of the each group.

Fig. 3.17 Histological sections of tumor tissues (a) Normal cells (b) EMT-6 (c) EMT-6 under exposure with 0.6 w/cm² laser for 2 min (d) EMT-6 with PSS-AuNRs injected (e) 1 day after photothermal treatment (f) 8 day after photothermal treatment

Fig. 3.17 shows that photothermal therapy can destroy the solid tumor structure and make severe destruction.

Chapter 4 Conclusion

All the experiments demonstrated the photothermal effect of PSS-AuNRs under NIR irradiation in destroying tumors cells in vitro and in vivo.

The results of photothermal therapy in in vitro experiments indicated that the destruction of tumors under photothermal therapy were related to the energy fluence of radiation as well as the clusters of PSS-AuNRs that tumors took up. Under the same energy fluence, the more clusters tumors took up, the severer the damage; within the same clusters, the higher energy the power fluence was, the greater the damage. According to the above results, the energy fluence for photothermal therapy, controlled within the medical safety level (100 mJ/cm²), was dependent on the amount of AuNRs taken up per cell.

When the solid tumors, where PSS-AuNRs were intratumorally injected, was irradiated by NIR laser, high thermal energy was generated from the optical excited PSS-AuNRs, which subsequently destroyed tumor cells in a noninvasive manner. The ability of photothermal therapy to completely eradicate the tumor cells is evident in the results shown in the growth curve and

histological sections of the tumor, yet the great amount of heat will also damage normal cells, like cartilage. In future practices of photothermal therapy, better experimental conditions should be the first priorities, including variables such as power density, exposure time, concentration of AuNRs, and model size.

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水產養殖學系 博士學位論文