Biological study of metal-organic frameworks towards human ovarian cancer cell lines
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abstract
Solvothermal chemistry was employed to produce PCN-95 starting with pyrene forming eight connected Zr6 clusters conforming to an isoreticular structure (P6/mmm). The secondary building unit was determined from polycrystals as having Zr6 center octahedral to and covering all triangular faces with eight OH and carboxylates as the framework. The polycordinated network material was characterized by electron microscopy and evaluated from its cytotoxicity against human ovarian cells. The concentration at 50% inhibition was in the low parts per million and electron micrographs showed a darker region around the DNA, indicative of DNA condensation leading to fragmentation. To determine whether the observed biological effects were due to the generation of singlet oxygen or elicitation of specific death pathways, the polycordinated network with and without select inhibitors or reducing and oxidizing agents was employed against human retinal pigment epithelium in vitro and NO measured as a measure of cell health against controls cells (without any cofactors). The NO release was measured a over 3 h time period and the kinetic plots compared and contrasted with known biochemical pathways. The plots were similar to methylene blue, a known singlet oxygen generator and between hydrogen peroxide and citrate but unlike cyanide or rotenone. Collectively, the results support the hypothesis of singlet oxygen generation at the mitochondria and interaction with complex IV of the electron transport chain, facilitating the reduction of nitrite towards more NO. When the cell generates higher concentrations of NO, the apoptotic pathways are triggered resulting in cell death.
