Nanoparticles increase the efficacy of cancer chemopreventive agents in cells exposed to cigarette smoke condensate

Alessandra Pulliero, Yun Wu, Daniela Fenoglio, Alessia Parodi, Massimo Romani, Christiane P. Soares, Gilberto Filaci, James L. Lee, Patrick N. Sinkam, Alberto Izzotti

Research output: Contribution to journalArticle

6 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)368-377
Number of pages10
JournalCarcinogenesis
Volume36
Issue number3
DOIs
Publication statusPublished - Jul 31 2014

Fingerprint

Smoke
Tobacco Products
Nanoparticles
Aptitude
Neoplasms
Lung Neoplasms
Acetylcysteine
DNA Fragmentation
Lipids
Biological Availability
Apoptosis
Annexin A5
Smoking Cessation
Developed Countries
Pharmaceutical Preparations
Cause of Death
Epithelial Cells
resveratrol
Staining and Labeling
phenethyl isothiocyanate

ASJC Scopus subject areas

  • Cancer Research
  • Medicine(all)

Cite this

Nanoparticles increase the efficacy of cancer chemopreventive agents in cells exposed to cigarette smoke condensate. / Pulliero, Alessandra; Wu, Yun; Fenoglio, Daniela; Parodi, Alessia; Romani, Massimo; Soares, Christiane P.; Filaci, Gilberto; Lee, James L.; Sinkam, Patrick N.; Izzotti, Alberto.

In: Carcinogenesis, Vol. 36, No. 3, 31.07.2014, p. 368-377.

Research output: Contribution to journalArticle

Pulliero, Alessandra ; Wu, Yun ; Fenoglio, Daniela ; Parodi, Alessia ; Romani, Massimo ; Soares, Christiane P. ; Filaci, Gilberto ; Lee, James L. ; Sinkam, Patrick N. ; Izzotti, Alberto. / Nanoparticles increase the efficacy of cancer chemopreventive agents in cells exposed to cigarette smoke condensate. In: Carcinogenesis. 2014 ; Vol. 36, No. 3. pp. 368-377.
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