PURPOSE: Oxidation therapy is an antitumor strategy in which, apoptosis or necrosis is caused by either excess delivery of reactive oxygen species (ROS) as an oxidant or anti-oxidant inhibition. Heme oxygenase (HO) is an anti-oxidant enzyme that plays an important role in cell growth and proliferation. The purpose of this study was to prepare poly lactic-co-glycolic acid (PLGA) nanoparticles (NPs) loaded with zinc protoporphyrin (ZnPP) to deliver the HO inhibitor into tumor. METHODS: PLGA NPs were prepared using nanoprecipitation technique and their characteristics were optimized by Box-Behnken experimental design. Scanning electron microscopy and in vitro studies consisting of drug release, HO inhibitory effect, cytotoxicity and cellular uptake followed by in vivo biodistribution and blood cytotoxicity were carried out. Internalization of coumerin-6 loaded NPs by PC3 cells was visualized by confocal laser scanning microscopy beside quantitatively analysis. RESULTS: NPs average size, entrapment efficiency and drug loading were 100.12 ± 5.345 nm, 55.6% ± 2.49 and 7.98% ± 0.341 respectively. Equal HO inhibitory effect of NPs compared to free ZnPP was observed. The IC50 value of ZnPP-NPs for PC3 human prostate cancer cells was found to be 2.14 ± 0.083 μM. CONCLUSION: In conclusion, ZnPP loaded PLGA NPs could exhibit enough HO inhibitory effect against cancer cells to be considered as a promising candidate for cancer treatment investigation.
PURPOSE: Oxidation therapy is an antitumor strategy in which, apoptosis or necrosis is caused by either excess delivery of reactive oxygen species (ROS) as an oxidant or anti-oxidant inhibition. Heme oxygenase (HO) is an anti-oxidant enzyme that plays an important role in cell growth and proliferation. The purpose of this study was to prepare poly lactic-co-glycolic acid (PLGA) nanoparticles (NPs) loaded with zinc protoporphyrin (ZnPP) to deliver the HO inhibitor into tumor. METHODS: PLGA NPs were prepared using nanoprecipitation technique and their characteristics were optimized by Box-Behnken experimental design. Scanning electron microscopy and in vitro studies consisting of drug release, HO inhibitory effect, cytotoxicity and cellular uptake followed by in vivo biodistribution and blood cytotoxicity were carried out. Internalization of coumerin-6 loaded NPs by PC3 cells was visualized by confocal laser scanning microscopy beside quantitatively analysis. RESULTS: NPs average size, entrapment efficiency and drug loading were 100.12 ± 5.345 nm, 55.6% ± 2.49 and 7.98% ± 0.341 respectively. Equal HO inhibitory effect of NPs compared to free ZnPP was observed. The IC50 value of ZnPP-NPs for PC3humanprostate cancer cells was found to be 2.14 ± 0.083 μM. CONCLUSION: In conclusion, ZnPP loaded PLGA NPs could exhibit enough HO inhibitory effect against cancer cells to be considered as a promising candidate for cancer treatment investigation.
Authors: Mariia R Mollaeva; Nikita Yabbarov; Maria Sokol; Margarita Chirkina; Murad D Mollaev; Artur Zabolotskii; Irina Seregina; Mikhail Bolshov; Alexander Kaplun; Elena Nikolskaya Journal: Int J Mol Sci Date: 2021-11-12 Impact factor: 5.923