Na, K-ATPase as a Biological Target for Gold(III) Complexes: A Theoretical and Experimental Approach.

BACKGROUND: Gold-based complexes represent a new class of potential metallodrugs. Although their action mechanism is not entirely understood, it was shown that gold complexes inhibit some enzymes' activities. Among them, Na,K-ATPase is emerging as an essential target for various anticancer drugs. The functionalization of nanoparticles by gold(III) complexes could facilitate their delivery into the cells and enable the following of their distribution in the target tissues. OBJECTIVE: The paper presents an overview of Na,K-ATPase interaction with representative and structurally related cytotoxic gold(III) complexes. The results obtained by the employment of theoretical methods (DFT and docking studies) combined with the experimental approach involving a variety of nanotechnology-base techniques (UV/Vis, Raman and fluorescence spectroscopy, CD, AFM, DLS) are discussed. Detailed information was obtained on the enzyme's conformational and structural changes upon binding the gold(III) complexes. The experimentally determined reaction parameters (constants of dissociation and the reaction stoichiometry) were predicted theoretically. CONCLUSION: The presented results offer further support to the view that Na,K-ATPase may be a relevant biomolecular target for cytotoxic gold(III) compounds of medicinal interest.

Discrimination among melanoma, nevi, and normal skin by using synchronous luminescence spectroscopy.

Novel optical spectroscopy and imaging methods may be valuable in the early detection of cancer. This paper reports differences in the luminescence responses of pigmented skin lesions (melanomas and nevi) and apparently normal non-pigmented human skin, based on analyses of synchronous luminescence spectroscopy measurements. Measurements were performed in the excitation range of 330-545 nm, with synchronous intervals varying from 30-120 nm. Normal skin, nevi, and melanomas differ in the way they fluoresce, and these differences are more distinct in the synchronous fluorescence spectra than in the conventional emission and excitation spectra. The differences in the fluorescence characteristics of pigmented and normal skin samples were ascribed to differences in concentrations of endogenous fluorophores and chromophores. Principal component and linear discriminant analysis of the synchronous spectra measured at different synchronous intervals showed that the greatest variance among the sample groups was at the 70 nm interval spectra. These spectra were then used to create partial least squares discriminant analysis-based classification models. Evaluation of the quality of these models from the receiver operating characteristic curves showed they performed well, with a maximum value of 1 for the area under the curve for melanoma detection. Hence, synchronous luminescence spectroscopy coupled with statistical methods may be advantageous in the early detection of skin cancer.

Support Vector Machine on fluorescence landscapes for breast cancer diagnostics.

Excitation-emission matrices (EEM) and total synchronous fluorescence spectra (SFS) of normal and malignant breast tissue specimens are measured in UV-VIS spectral region to serve as data inputs in development of Support Vector Machine (SVM) based breast cancer diagnostics tool. Various input data combinations are tested for classification accuracy using SVM prediction against histopathology findings to discover the best combination regarding diagnostics sensitivity and specificity. It is shown that with EEM data SVM provided 67% sensitivity and 62% specificity diagnostics. With SFS data SVM provided 100% sensitivity and specificity for a several input data combinations. Among these combinations those that require minimal data inputs are identified.