title: Zinc protoporphyrin polymeric nanoparticles: potent heme oxygenase inhibitor for cancer therapy.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.affiliation: Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Hasti
authors.initials: H
authors.lastname: Rouhani
authors.forename: Nima
authors.initials: N
authors.lastname: Sepehri
authors.forename: Hamed
authors.initials: H
authors.lastname: Montazeri
authors.forename: Mohammad Reza
authors.initials: MR
authors.lastname: Khoshayand
authors.forename: Mohammad Hossein
authors.initials: MH
authors.lastname: Ghahremani
authors.forename: Seyed Nasser
authors.initials: SN
authors.lastname: Ostad
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Atyabi
authors.forename: Rassoul
authors.initials: R
authors.lastname: Dinarvand
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D006419:Heme Oxygenase (Decyclizing) / Q000037:antagonists & inhibitors*; D006801:Humans; D008297:Male; D053768:Metal Nanoparticles / Q000627:therapeutic use; D051379:Mice; D008807:Mice, Inbred BALB C; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism; D010316:Particle Size; D011108:Polymers / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D011524:Protoporphyrins / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats
chemical_list: D000970:Antineoplastic Agents; D011108:Polymers; D011524:Protoporphyrins; C017803:zinc protoporphyrin; D006419:Heme Oxygenase (Decyclizing)