ABSTRACT
Cancer cells are more susceptible to H2O2 induced cell death than normal cells. H2O2-activatable and O2-evolving nanoparticles could be used as photodynamic therapy agents in hypoxic environments. In this report, a photo-active Mn(II) complex of boradiazaindacene derivatives (Mn1) was used as a dioxygen generator under irradiation with LED light in water. Moreover, the in vitro biological evaluation for Mn1 and its loaded graphene oxide (herein called Mn1@GO) on HepG-2 cells in normal and hypoxic conditions has been performed. In particular, Mn1@GO can react with H2O2 resulting active anticancer species, which show high inhibition on both HepG-2 cells and CoCl2-treated HepG-2 cells (hypoxic cancer cells). The mechanism of LED light enhanced anticancer activity for Mn1@GO on HepG-2 cells was discussed. Our results show that Mn(II) complexes of boradiazaindacene (BODIPY) derivatives loaded GO can be both LED light and H2O2-activated anticancer agents in hypoxic environments.
Subject(s)
Boron Compounds , Cobalt , Graphite , Hydrogen Peroxide/pharmacology , Light , Antineoplastic Agents , Boron Compounds/chemistry , Boron Compounds/pharmacology , Cobalt/chemistry , Cobalt/pharmacology , Drug Screening Assays, Antitumor , Graphite/chemistry , Graphite/pharmacology , Hep G2 Cells , HumansABSTRACT
The iron complex [(m-BDA)FeCl3] (Fe1) (m-BDA=8-[di(2-picolyl)amine-3-benzyl]-4,4-difluoro-1,3,5,7-tetramethyl-4-bora-3a,4a-diaza-s-indacene) was characterized by spectroscopic methods. The emission intensity of Fe1 is weaker than that of m-BDA due to the electrostatic interaction between the Fe(III) ion and m-BDA. However, the coordination of water with the central Fe(III) ion in Fe1 changed metal-ligand charge transfer, thus the quenched emission at 509 nm was recovered. Furthermore, Fe1 can catalyze water oxidation to generate dioxygen when irradiated by green LED light (10W). In particular, the Fe1 can enter into HepG-2 cells and show different inhibition rates in black and under irradiation. The anticancer activity of Fe1 was greatly enhanced under irradiation. Our results demonstrate that Fe(III) complexes of BODIPY can be developed as new kinds of photodynamic agents.
Subject(s)
Boron Compounds/chemistry , Ferric Compounds/chemistry , Amines/chemistry , Catalysis , Electrochemical Techniques , Ferric Compounds/pharmacokinetics , Ferric Compounds/toxicity , Fluorescent Dyes/chemistry , HeLa Cells , Hep G2 Cells , Humans , Hydrogen-Ion Concentration , Molecular Imaging/methods , Oxidation-Reduction , Picolinic Acids/chemistry , Spectrophotometry, Ultraviolet , Spectrum Analysis, Raman , Water/chemistryABSTRACT
In order to confirm the neurotoxicity of bifunctional chelators containing hydrophobic groups and metal chelating moiety, the interaction of di(picolyl)amine (dpa) derivatives toward Aß42 peptide was investigated. Fluorescence titration reveals that a hydrophobic chelator (such as BODIPY) shows high binding affinity to amyloid Aß42. Circular dichroism (CD) spectra confirm that the hydrophobic bifunctional chelator can decrease α-helix fraction and increase the ß-sheet fraction of amyloid Aß42. In particular, experimental results indicate that a bifunctional chelator can assemble with Cu(II)-Aß42 forming chelator-Cu(II)-Aß42 nanospheres, which are toxic to SH-S5Y5 cells. The hydrophobic interaction between the chelator and the amyloid peptide (Aß42) has great contribution to the formation of neurotoxic chelator-Cu(II)-Aß42 nanospheres. This work gives a general guide to the development of low cytotoxic inhibitors of Aß42 aggregation.
Subject(s)
Amyloid beta-Peptides/chemistry , Peptide Fragments/chemistry , Alzheimer Disease , Cell Line, Tumor , Chelating Agents/chemistry , Circular Dichroism , Copper/chemistry , Humans , Microscopy, Electron, Transmission , Protein Structure, Secondary , Spectrometry, Fluorescence , Spectrum Analysis , Zinc/chemistryABSTRACT
Lactate dehydrogenase A (LDH-A) is a potentially important metabolic target for the inhibition of the highly activated glycolysis pathway in cancer cells. Two Mn(II) complexes with ligand containing di(pyridylmethyl) amine and pyrrol-ketone were used to attenuate the activity of LDH-A. The inhibition of the manganese(II) complexes on the proliferation of HepG-2 cells is related to their ability to disproportionate H2O2. Importantly, the synthesized mimic of catalase can decrease the expression of hypoxia inducible factor (HIF-1α) in HepG-2 cells. So we envision that the multifunctional mimics of catalase could attenuate the activity of LDH-A signaling the cancer cells to death through HIF-1α involved path.
