title: Photothermal therapy mediated by gum Arabic-conjugated gold nanoparticles suppresses liver preneoplastic lesions in mice.
abstract: This study validates the utility of Gum Arabic-conjugated gold nanoparticles (GA-AuNPs) and laser to induce photothermal inhibition of hepatocarcinogenesis, via employing a diethylnitrosamine (DEN)-mediated hepatocellular carcinoma model. This work included both of in vitro and in vivo studies; to investigate the GA-AuNPs cytotoxicity and phototoxicity in hepatic cell line; to delineate the GA-AuNPs therapeutic efficiency in DEN-induced preneoplastic lesions (PNLs) in the liver of Balb-C mice. The therapeutic effects of GA-AuNPs on the mediators of apoptosis, inflammation, and tumor initiation, as well as the histopathological changes in preneoplastic liver have been investigated. Our results infer that GA-AuNPs in combination with laser irradiation led to a significant reduction in the cell viability and in histone deacetylase activity in hepatocarcinoma HepG2 cells. In chemically-induced PNLs mice model our results have demonstrated that GA-AuNPs, with or without laser irradiation, induced cancer cell apoptosis through the activation of death receptors DR5 and caspase-3 and inhibited both of the PNLs incidence and the initiation marker (placental glutathione S-transferase; GST-P). The laser-stimulated GA-AuNPs significantly reduced the tumor necrosis factor-α levels. In summary, GA-AuNPs with laser treatment inhibited liver PNLs via the induction of the extrinsic apoptosis pathway and the inhibition of inflammation.
authors.affiliation: Cancer Biology and Genetics Laboratory, Centre of Excellence for Advanced Sciences, National Research Centre, Cairo, Egypt; Department of Biochemistry, National Research Centre, Cairo, Egypt. Electronic address: aeldeen7@yahoo.com.
authors.forename: Amira M
authors.initials: AM
authors.lastname: Gamal-Eldeen
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, October 6 University, 6 October City, Giza, Egypt.
authors.forename: Dina
authors.initials: D
authors.lastname: Moustafa
authors.affiliation: Cancer Biology and Genetics Laboratory, Centre of Excellence for Advanced Sciences, National Research Centre, Cairo, Egypt; Department of Medical Biochemistry, National Research Centre, Cairo, Egypt.
authors.forename: Sherien M
authors.initials: SM
authors.lastname: El-Daly
authors.affiliation: Zoology Department, Faculty of Science, Ain Shams University, Cairo, Egypt.
authors.forename: Enas A
authors.initials: EA
authors.lastname: El-Hussieny
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
authors.forename: Samira
authors.initials: S
authors.lastname: Saleh
authors.affiliation: Department of Radiology, University of Missouri, Columbia, MO 65212, USA; Institute of Green Nanotechnology, University of Missouri, Columbia, MO 65212, USA.
authors.forename: Menka
authors.initials: M
authors.lastname: Khoobchandani
authors.affiliation: Department of Radiology, University of Missouri, Columbia, MO 65212, USA; Institute of Green Nanotechnology, University of Missouri, Columbia, MO 65212, USA.
authors.forename: Kathryn L
authors.initials: KL
authors.lastname: Bacon
authors.affiliation: Department of Radiology, University of Missouri, Columbia, MO 65212, USA; Institute of Green Nanotechnology, University of Missouri, Columbia, MO 65212, USA; Department of Physics, University of Missouri, Columbia, MO 65212, USA; Department of Bioengineering, University of Missouri, Columbia, MO 65211, USA.
authors.forename: Sagar
authors.initials: S
authors.lastname: Gupta
authors.affiliation: Department of Radiology, University of Missouri, Columbia, MO 65212, USA; Institute of Green Nanotechnology, University of Missouri, Columbia, MO 65212, USA.
authors.forename: Kavita
authors.initials: K
authors.lastname: Katti
authors.affiliation: Centre for Advanced Materials and Industrial Chemistry; School of Applied Sciences; Health Innovation Research Institute; RMIT University, Australia.
authors.forename: Ravi
authors.initials: R
authors.lastname: Shukla
authors.affiliation: Department of Radiology, University of Missouri, Columbia, MO 65212, USA; Institute of Green Nanotechnology, University of Missouri, Columbia, MO 65212, USA; Research Reactor, University of Missouri, Columbia, MO 65212, USA; Department of Physics, University of Missouri, Columbia, MO 65212, USA; Department of Bioengineering, University of Missouri, Columbia, MO 65211, USA.
authors.forename: Kattesh V
authors.initials: KV
authors.lastname: Katti
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D002471:Cell Transformation, Neoplastic; D004052:Diethylnitrosamine / Q000009:adverse effects; D051549:Glutathione S-Transferase pi / Q000378:metabolism; D006046:Gold / Q000737:chemistry*; D006170:Gum Arabic / Q000737:chemistry* / Q000494:pharmacology*; D056945:Hep G2 Cells; D051548:Histone Acetyltransferases / Q000378:metabolism; D006801:Humans; D008113:Liver Neoplasms / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D053768:Metal Nanoparticles / Q000737:chemistry*; D051379:Mice; D009336:Necrosis; D010789:Phototherapy / Q000379:methods*; D011230:Precancerous Conditions / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D018809:Proliferating Cell Nuclear Antigen; D014409:Tumor Necrosis Factor-alpha; D004052:Diethylnitrosamine; D006046:Gold; D006170:Gum Arabic; D051548:Histone Acetyltransferases; D051549:Glutathione S-Transferase pi
keywords: Apoptosis; GST-P; Gold nanoparticles; Gum Arabic; Photothermal; Preneoplastic lesions