title: Nanoparticles increase the efficacy of cancer chemopreventive agents in cells exposed to cigarette smoke condensate.
abstract: Lung cancer is a leading cause of death in developed countries. Although smoking cessation is a primary strategy for preventing lung cancer, former smokers remain at high risk of cancer. Accordingly, there is a need to increase the efficacy of lung cancer prevention. Poor bioavailability is the main factor limiting the efficacy of chemopreventive agents. The aim of this study was to increase the efficacy of cancer chemopreventive agents by using lipid nanoparticles (NPs) as a carrier. This study evaluated the ability of lipid NPs to modify the pharmacodynamics of chemopreventive agents including N-acetyl-L-cysteine, phenethyl isothiocyanate and resveratrol (RES). The chemopreventive efficacy of these drugs was determined by evaluating their abilities to counteract cytotoxic damage (DNA fragmentation) induced by cigarette smoke condensate (CSC) and to activate protective apoptosis (annexin-V cytofluorimetric staining) in bronchial epithelial cells both in vitro and in ex vivo experiment in mice. NPs decreased the toxicity of RES and increased its ability to counteract CSC cytotoxicity. NPs significantly increased the ability of phenethyl isothiocyanate to attenuate CSC-induced DNA fragmentation at the highest tested dose. In contrast, this potentiating effect was observed at all tested doses of RES, NPs dramatically increasing RES-induced apoptosis in CSC-treated cells. These results provide evidence that NPs are highly effective at increasing the efficacy of lipophilic drugs (RES) but are not effective towards hydrophilic agents (N-acetyl-L-cysteine), which already possess remarkable bioavailability. Intermediate effects were observed for phenethyl isothiocyanate. These findings are relevant to the identification of cancer chemopreventive agents that would benefit from lipid NP delivery.
authors: Department of Health Sciences, University of Genoa, 16132 Genoa, Italy.
authors: Alessandra
authors: A
authors: Pulliero
authors: Nanoscale Science and Engineering Center for Affordable Nano-engineering of Polymeric Biomedical Devices, The Ohio State University, Columbus, OH 43210, USA.
authors: Yun
authors: Y
authors: Wu
authors: Centre of Excellence for Biomedical Research and Department of Internal Medicine, University of Genoa, 16132 Genoa, Italy.
authors: Daniela
authors: D
authors: Fenoglio
authors: Centre of Excellence for Biomedical Research and.
authors: Alessia
authors: A
authors: Parodi
authors: Mutagenesis Unit, IRCCS AOU (Institute for Hospitalization and Cure with Scientific Character) San Martino-IST Genoa, 16132 Genoa, Italy.
authors: Massimo
authors: M
authors: Romani
authors: Mutagenesis Unit, IRCCS AOU (Institute for Hospitalization and Cure with Scientific Character) San Martino-IST Genoa, 16132 Genoa, Italy.
authors: Christiane P
authors: CP
authors: Soares
authors: Centre of Excellence for Biomedical Research and Department of Internal Medicine, University of Genoa, 16132 Genoa, Italy.
authors: Gilberto
authors: G
authors: Filaci
authors: Nanoscale Science and Engineering Center for Affordable Nano-engineering of Polymeric Biomedical Devices, The Ohio State University, Columbus, OH 43210, USA, William G. Lowrie Department of Chemical and Bimolecular Engineering, 125A Koffolt Labs and.
authors: James L
authors: JL
authors: Lee
authors: Division of Pulmonary Allergy, Critical Care and Sleep Medicine, The Ohio State University, Columbus, OH 43210, USA.
authors: Patrick N
authors: PN
authors: Sinkam
authors: Department of Health Sciences, University of Genoa, 16132 Genoa, Italy, Mutagenesis Unit, IRCCS AOU (Institute for Hospitalization and Cure with Scientific Character) San Martino-IST Genoa, 16132 Genoa, Italy, izzotti@unige.it.
authors: Alberto
authors: A
authors: Izzotti
mesh_terms: D000111:Acetylcysteine / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D000818:Animals; D016588:Anticarcinogenic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001984:Bronchial Neoplasms / Q000188:drug therapy; D045744:Cell Line, Tumor; D006801:Humans; D017879:Isothiocyanates / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D008815:Mice, Inbred Strains; D053758:Nanoparticles; D000077185:Resveratrol; D012907:Smoking / Q000009:adverse effects*; D013267:Stilbenes / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D014028:Tobacco Smoke Pollution
chemical_list: D016588:Anticarcinogenic Agents; D017879:Isothiocyanates; D013267:Stilbenes; D014028:Tobacco Smoke Pollution; C058305:phenethyl isothiocyanate; D000077185:Resveratrol; D000111:Acetylcysteine