tetraphenylporphine and Breast-Neoplasms

In the search for photosensitizers with chemical handles to facilitate their integration into complex drug delivery nanosystems, new, unsymmetrically substituted, water insoluble meso-tetraphenylporphyrin and meso-tetra(m-hydroxyphenyl)porphyrin derivatives bearing one carboxyalkyl side chain were synthesized. Permethyl-β-cyclodextrin (pMβCD) was their ideal monomerizing host and highly efficient shuttle to transfer them into water. New assembly modes of the extremely stable (K

Topics: beta-Cyclodextrins; Biological Transport; Breast Neoplasms; Drug Carriers; Drug Delivery Systems; Endoplasmic Reticulum; Female; Humans; Magnetic Resonance Spectroscopy; MCF-7 Cells; Photosensitizing Agents; Porphyrins; Solubility; Spectrometry, Fluorescence; Water

Tumor cells adapt to reactive oxygen species (ROS) attacking by launching DNA damage repairing mechanisms such as nucleotide pool sanitizing enzyme mutt homologue 1 (MTH1) to mitigate the oxidatively induced DNA lesions, which could greatly limit the therapeutic efficiency of current oxidation therapy. Here, an amplified oxidative damage strategy for tumor therapy was proposed that was focused not only on the enhancement of ROS generation but also the inhibition of subsequent MTH1 enzyme activity simultaneously. In our formulation, mesoporous silica-coated Prussian blue nanoplatforms (PB@MSN) with excellent catalase-like activity and drug loading capability were employed to encapsulate MTH1 inhibitor TH287, followed by the modification of tetraphenylporphrin zinc (Zn-Por) via metallo-supramolecular coordination (PMPT), where Zn-Por behaved as photodynamic and fluorescence imaging agents, as well as acid-responsive gatekeepers. The intelligent PMPT nanosystems could induce the decomposition of H

Topics: Animals; Breast Neoplasms; DNA Repair Enzymes; Enzyme Inhibitors; Female; Humans; MCF-7 Cells; Mice, Nude; Optical Imaging; Oxidative Stress; Phosphoric Monoester Hydrolases; Photochemotherapy; Photosensitizing Agents; Porphyrins; Pyrimidines; Reactive Oxygen Species