Ligand Dictated Photosensitization of Iridium(III) Dithiocarbamate Complexes for Photodynamic Therapy.

Organelle-targeted photosensitizers (PSs) for photodynamic therapy (PDT) are considered as an effective therapeutic strategy for the development of next generation PSs with the least side effects and high therapeutic efficacy. However, multiorganelle targeted PSs eliciting PDT via both type I and type II mechanisms are scarce. Herein, a series of cyclometalated iridium(III) complexes were formulated [Ir(C∧N)2(S∧S)] (C∧N = 2-phenylpyridine (ppy) and 2-(thiophen-2-yl)pyridine (thpy); S∧S = diethyldithiocarbamate (DEDTC), morpholine-N-dithiocarbamate (MORDTC) and methoxycarbonodithioate (MEDTC)) and the newly designed complexes Ir2@DEDTC and Ir1@MEDTC were characterized by single crystal X-ray crystallography. Complexes containing thpy as C∧N ligand exhibit excellent photophysical properties such as red-shifted emission, high singlet oxygen quantum yield (ϕΔ) and longer photoluminescence lifetime when compared with complexes containing ppy ligands. Ir2@DEDTC exhibits the highest Ï•Δ and photoluminescence lifetimes among the synthesized complexes. Therefore, Ir2@DEDTC was chosen to evaluate the photosensitizing ability to produce reactive oxygen species (ROS). Upon blue light irradiation (456 nm), it efficiently produces ROS, i.e., hydroxy radical (•OH) and singlet oxygen (1O2), which was confirmed by electron paramagnetic resonance (EPR) spectroscopy. In vitro photocytotoxicity toward HCT116, HeLa, and PC3 cell lines showed that out of all the synthesized complexes, Ir2@DEDTC has the highest photocytotoxic index (PI > 400) value. Ir2@DEDTC is efficiently taken up by the HCT116 cell line and accumulated mainly in the lysosome and mitochondria of the cells, and after PDT treatment, it elicits cell shrinkage, membrane blebbing, and DNA fragmentation. The phototherapeutic efficacy of Ir2@DEDTC has been investigated against 3D spheroids considering its ability to mimic some of the basic features of solid tumors. The morphology was drastically altered in the Ir2@DEDTC treated 3D spheroid after the light irradiation unleashed the potential of the Ir(III) dithiocarbamate complex as a superior PS for PDT. Hence, mitochondria and lysosome targeted photoactive cyclometalated Ir(III) dithiocarbamate complex exerting oxidative stress via both type I and type II PDT can be regarded as a dual-organelle targeted two-pronged approach for enhanced PDT.

Prevalence of oral parameters in smokeless tobacco-associated precancer.

AIM: To evaluate and correlate the prevalence of Candida species, salivary flow rate, pH, and buffer capacity of oral cavity in subjects with leukoplakia, tobacco pouch keratosis, and healthy controls. MATERIALS AND METHODS: In this prospective study, a total of 25 cases of leukoplakia, 25 of tobacco pouch keratosis, and 50 of healthy controls were studied. Sabouraud's dextrose agar (SDA) for the identification of Candida and HiCrome Candida differential Agar for the species identification of Candida were used. Calculation of salivary flow rate, pH, and buffer capacity was done with Saliva-Check Buffer kit (GC). RESULTS: The prevalence of Candida carriage obtained was considerably greater in the study group associated with smokeless tobacco use. NonCandida albicans Candida species predominated over Candida albicans in speciation among study groups on HiCrome agar and Candida albicans predominated among control groups. Statistically significant values were obtained by comparing the salivary flow rate, pH, and buffer capacity between the study groups and control groups. CONCLUSION: The present study indicated Candida prevalence was seen more in study group than healthy control groups, suggesting increased Candida in smokeless tobacco users. The prevalence of NonCandida albicans Candida species among leukoplakia and tobacco pouch keratosis indicates that there is pervasiveness of significant NonCandida albican Candida species in relation to salivary flow rate and buffer capacity. Therefore, the choice of antifungal treatment promptly must deal with not only resistance but, similarly, with the transformation in predominance from Candida albicans to NonCandida albicans Candida species. The numbers of sample study were considerably less to conclude such result hence, numbers of studies should be performed at larger scale in the particular area.