PURPOSE: The comparison between sonodynamic antitumor effect with protoporphyrin IX (PPIX) and hematoporphyrin (Hp) at a concentration of 5 mg/kg on Sarcoma 180 (S180) cells was studied in vivo, and the potential cell damage mechanism was also investigated. METHODS: The sonodynamically induced anti-tumor effect of PPIX was studied in mice bearing S180 solid tumors. In order to determine the optimum timing of ultrasound exposure after administration of PPIX, the PPIX concentrations in plasma, skin, muscle and tumor were determined by the fluorescence intensity of tissue extractions with a fluorescence spectrophotometer based on the standard curve. Anti-tumor effects were estimated by measuring the tumor size and the tumor weight. Additionally, the morphological changes of S180 cells were evaluated by transmission electron microscope (TEM) observation immediately after sonodynamic therapy (SDT) treatment. RESULTS: A time of 24 h after the intravenous administration of PPIX was chosen as the best time for ultrasound exposure. The antitumor effect induced by PPIX mediated sonodynamic therapy (PPIX-SDT) was in a dose dependent manner when ultrasound intensity was at or above the inertial cavitation threshold (5 W/cm(2)). A significant tumor growth delay was observed both in PPIX mediated sonodynamic therapy and in Hp mediated sonodynamic therapy treatments (Hp-SDT), and the tumor weight inhibition ratios after the synergistic treatments were 42.82 +/- 0.03 and 35.22 +/- 0.03%, respectively, this difference was significant at P < 0.05. While ultrasound alone (5 W/cm(2)) showed a slight tumor growth inhibitory effect compared with the control group, and PPIX or Hp alone showed almost no significant effect. Furthermore, TEM observation indicated cell damage was more serious in PPIX-SDT treatment group than in Hp-SDT treatment group. After sonication, the cell ultra-structure such as cell membrane destruction, mitochondria swelling, chromatin condensation might be important factors that inhibited the tumor growth and even induced cell death. CONCLUSIONS: The comparative results suggested that PPIX as a sonosensitizer might have more potential cytotoxicity than Hp when irradiated with ultrasound, and the ultra-structural changes may account for cell destruction induced by sonodynamic therapy in our experiment mode.
PURPOSE: The comparison between sonodynamic antitumor effect with protoporphyrin IX (PPIX) and hematoporphyrin (Hp) at a concentration of 5 mg/kg on Sarcoma 180 (S180) cells was studied in vivo, and the potential cell damage mechanism was also investigated. METHODS: The sonodynamically induced anti-tumor effect of PPIX was studied in mice bearing S180 solid tumors. In order to determine the optimum timing of ultrasound exposure after administration of PPIX, the PPIX concentrations in plasma, skin, muscle and tumor were determined by the fluorescence intensity of tissue extractions with a fluorescence spectrophotometer based on the standard curve. Anti-tumor effects were estimated by measuring the tumor size and the tumor weight. Additionally, the morphological changes of S180 cells were evaluated by transmission electron microscope (TEM) observation immediately after sonodynamic therapy (SDT) treatment. RESULTS: A time of 24 h after the intravenous administration of PPIX was chosen as the best time for ultrasound exposure. The antitumor effect induced by PPIX mediated sonodynamic therapy (PPIX-SDT) was in a dose dependent manner when ultrasound intensity was at or above the inertial cavitation threshold (5 W/cm(2)). A significant tumor growth delay was observed both in PPIX mediated sonodynamic therapy and in Hp mediated sonodynamic therapy treatments (Hp-SDT), and the tumor weight inhibition ratios after the synergistic treatments were 42.82 +/- 0.03 and 35.22 +/- 0.03%, respectively, this difference was significant at P < 0.05. While ultrasound alone (5 W/cm(2)) showed a slight tumor growth inhibitory effect compared with the control group, and PPIX or Hp alone showed almost no significant effect. Furthermore, TEM observation indicated cell damage was more serious in PPIX-SDT treatment group than in Hp-SDT treatment group. After sonication, the cell ultra-structure such as cell membrane destruction, mitochondria swelling, chromatin condensation might be important factors that inhibited the tumor growth and even induced cell death. CONCLUSIONS: The comparative results suggested that PPIX as a sonosensitizer might have more potential cytotoxicity than Hp when irradiated with ultrasound, and the ultra-structural changes may account for cell destruction induced by sonodynamic therapy in our experiment mode.
Authors: Gun Kim; Qiong Wu; James L Chu; Emily J Smith; Michael L Oelze; Jeffrey S Moore; King C Li Journal: Proc Natl Acad Sci U S A Date: 2022-01-25 Impact factor: 12.779