Liposome armed with herpes virus-derived gH625 peptide to overcome doxorubicin resistance in lung adenocarcinoma cell lines
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Emiliana Perillo1,*, Stefania Porto2,*, Annarita Falanga1, Silvia Zappavigna2, Paola Stiuso2, Virginia Tirino3, Vincenzo Desiderio3, Gianpaolo Papaccio3, Massimiliano Galdiero4, Antonio Giordano5,6, Stefania Galdiero1, Michele Caraglia2,5,6
1Department of Pharmacy and DFM Scarl - University of Naples “Federico II”, Naples, Italy
2Department of Biochemistry, Biophysics and General Pathology, Second University of Naples, Naples, Italy
3Department of Experimental Medicine, Section of Biotechnology and Medical Histology and Embryology, Second University of Naples, Naples, Italy
4Department of Experimental Medicine - Second University of Naples, Naples, Italy
5Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, College of Science and Technology, Temple University, Philadelphia, PA, USA
6Department of Medicine, Surgery and Neuroscience, University of Siena, Siena, Italy
*These authors have equally contributed to this work
Stefania Galdiero, e-mail: [email protected]
Keywords: doxorubicin, drug resistance, membranotropic peptide, liposome, lung adenocarcinoma
Received: July 01, 2015 Accepted: October 27, 2015 Published: November 06, 2015
New delivery systems including liposomes have been developed to circumvent drug resistance. To enhance the antitumor efficacy of liposomes encapsulating anti-cancer agents, we used liposomes externally conjugated to the 20 residue peptide gH625. Physicochemical characterization of the liposome system showed a size of 140 nm with uniform distribution and high doxorubicin encapsulation efficiency. We evaluated the effects of increasing concentrations of liposomes encapsulating Doxo (LipoDoxo), liposomes encapsulating Doxo conjugated to gH625 (LipoDoxo-gH625), empty liposomes (Lipo) or free Doxo on growth inhibition of either wild type (A549) or doxorubicin-resistant (A549 Dx) human lung adenocarcinoma. After 72 h, we found that the growth inhibition induced by LipoDoxo-gH625 was higher than that caused by LipoDoxo with an IC50 of 1 and 0.3 μM in A549 and A549 Dx cells, respectively. The data on cell growth inhibition were paralleled by an higher oxidative stress and an increased uptake of Doxo induced by LipoDoxo-gH625 compared to LipoDoxo, above all in A549 Dx cells. Cytometric analysis showed that the antiproliferative effects of each drug treatment were mainly due to the induction of apoptosis. In conclusion, liposomes armed with gH625 are able to overcome doxorubicin resistance in lung adenocarcinoma cell lines.
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