Cisplatin and photodynamic therapy exert synergistic inhibitory effects on small-cell lung cancer cell viability and xenograft tumor growth.

Lung cancer is the leading cause of cancer death worldwide. Small-cell lung cancer (SCLC) is an aggressive type of lung cancer that shows an overall 5-year survival rate below 10%. Although chemotherapy using cisplatin has been proven effective in SCLC treatment, conventional dose of cisplatin causes adverse side effects. Photodynamic therapy, a form of non-ionizing radiation therapy, is increasingly used alone or in combination with other therapeutics in cancer treatment. Herein, we aimed to address whether low dose cisplatin combination with PDT can effectively induce SCLC cell death by using in vitro cultured human SCLC NCI-H446 cells and in vivo tumor xenograft model. We found that both cisplatin and PDT showed dose-dependent cytotoxic effects in NCI-H446 cells. Importantly, co-treatment with low dose cisplatin (1 µM) and PDT (1.25 J/cm2) synergistically inhibited cell viability and cell migration. We further showed that the combined therapy induced a higher level of intracellular ROS in cultured NCI-H446 cells. Moreover, the synergistic effect by cisplatin and PDT was recapitulated in tumor xenograft as revealed by a more robust increase in the staining of TUNEL (a marker of cell death) and decrease in tumor volume. Taken together, our findings suggest that low dose cisplatin combination with PDT can be an effective therapeutic modality in the treatment of SCLC patients.

Enzyme activated photodynamic therapy for methicillin-resistant Staphylococcus aureus infection both inv itro and in vivo.

In recent years, methicillin-resistant Staphylococcus aureus (MRSA) has become one of the most common multi-drug resistant bacteria in both hospital and community. The aim of this study is to investigate the selective inhibition of MRSA by a modified photosensitizer (LAEtNBS) in vitro and the efficacy of MRSA infection treatment by photodynamic therapy (PDT) with LAEtNBS in vivo. LAEtNBS was synthesized by adding a cationic photosensitizer molecule (EtNBS-COOH) and a quencher molecule to two side chains of cephalosporin, which was then shown to have similar absorption and emission wavelengths with EtNBS-COOH, but suppressed yields of fluorescence quantum and singlet oxygen. The selective inactivation and less phototoxicity of LAEtNBS, compared to that of EtNBS-COOH, were assessed and confirmed by conducting PDT to two Staphylococcus aureus strains and human skin cells at a fluence of 15 J/cm(2) with 640±10 nm LED light. Furthermore, using mouse skin wound model infected with 10(8) CFU of MRSA, we found that both LAEtNBS and EtNBS-COOH were able to treat MRSA infection and enhance wound repair. However, there was no significant difference in the two photosensitizers that might be due to the environment in vivo. Modification of the photosensitizer will be very beneficial for developing new strategies to treat drug resistant bacterial infection with less harm to host tissue.