Abraham H Abouzeid1, Niravkumar R Patel, Can Sarisozen, Vladimir P Torchilin. 1. Department of Pharmaceutical Sciences Center for Pharmaceutical Biotechnology and Nanomedicine, Northeastern University, 140 The Fenway, Room 236, 360 Huntington Ave., Boston, Massachusetts, 02115, USA.
Abstract
PURPOSE: The ability to successfully treat advanced forms of cancer remains a challenge due to chemotherapy resistance. Numerous studies indicate that NF-κB, a protein complex that controls the expression of numerous genes, as being a key factor in producing chemo-resistant tumors. In this study, the therapeutic potential of transferrin (TF)-targeted mixed micelles, made of PEG-PE and vitamin E co-loaded with curcumin (CUR), a potent NF-κB inhibitor, and paclitaxel (PCL), was examined. METHODS: The cytotoxicity of non-targeted and TF-targeted CUR and PCL micelles as a single agent or in combination was investigated against SK-OV-3 human ovarian adenocarcinoma along with its multi-drug resistant (MDR) version SK-OV-3-PCL-resistant (SK-OV-3TR) cells in vitro. RESULTS: Our results indicated that the TF-targeted combination micelles were able to improve the net cytotoxic effect of CUR and PCL to clear synergistic one against the SK-OV-3 cells. In addition, even though the non-targeted combination treatment demonstrated a synergistic effect against the SK-OV-3TR cells, the addition of the TF-targeting moiety significantly increased this cytotoxic effect. While keeping CUR constant at 5 and 10 μM and varying the PCL concentration, the PCL IC50 decreased from ~1.78 to 0.68 μM for the non-targeted formulations to ~0.74 and 0.1 μM for the TF-targeted ones, respectively. CONCLUSION: Our results indicate that such co-loaded targeted mixed micelles could have significant clinical advantages for the treatment of resistant ovarian cancer and provide a clear rational for further in vivo investigation.
PURPOSE: The ability to successfully treat advanced forms of cancer remains a challenge due to chemotherapy resistance. Numerous studies indicate that NF-κB, a protein complex that controls the expression of numerous genes, as being a key factor in producing chemo-resistant tumors. In this study, the therapeutic potential of transferrin (TF)-targeted mixed micelles, made of PEG-PE and vitamin E co-loaded with curcumin (CUR), a potent NF-κB inhibitor, and paclitaxel (PCL), was examined. METHODS: The cytotoxicity of non-targeted and TF-targeted CUR and PCL micelles as a single agent or in combination was investigated against SK-OV-3 humanovarian adenocarcinoma along with its multi-drug resistant (MDR) version SK-OV-3-PCL-resistant (SK-OV-3TR) cells in vitro. RESULTS: Our results indicated that the TF-targeted combination micelles were able to improve the net cytotoxic effect of CUR and PCL to clear synergistic one against the SK-OV-3 cells. In addition, even though the non-targeted combination treatment demonstrated a synergistic effect against the SK-OV-3TR cells, the addition of the TF-targeting moiety significantly increased this cytotoxic effect. While keeping CUR constant at 5 and 10 μM and varying the PCL concentration, the PCL IC50 decreased from ~1.78 to 0.68 μM for the non-targeted formulations to ~0.74 and 0.1 μM for the TF-targeted ones, respectively. CONCLUSION: Our results indicate that such co-loaded targeted mixed micelles could have significant clinical advantages for the treatment of resistant ovarian cancer and provide a clear rational for further in vivo investigation.
Authors: Vineesh Indira Chandran; Lidia Matesic; Julie M Locke; Danielle Skropeta; Marie Ranson; Kara L Vine Journal: Cancer Lett Date: 2011-11-22 Impact factor: 8.679
Authors: H J Arts; D Katsaros; E G de Vries; M Massobrio; F Genta; S Danese; R Arisio; R J Scheper; M Kool; G L Scheffer; P H Willemse; A G van der Zee; A J Suurmeijer Journal: Clin Cancer Res Date: 1999-10 Impact factor: 12.531
Authors: Tracy R Daniels; Ezequiel Bernabeu; José A Rodríguez; Shabnum Patel; Maggie Kozman; Diego A Chiappetta; Eggehard Holler; Julia Y Ljubimova; Gustavo Helguera; Manuel L Penichet Journal: Biochim Biophys Acta Date: 2011-08-05
Authors: Smitha V Bava; Chanickal N Sreekanth; Arun Kumar T Thulasidasan; Nikhil P Anto; Vino T Cheriyan; Vineshkumar T Puliyappadamba; Sajna G Menon; Santhosh D Ravichandran; Ruby John Anto Journal: Int J Biochem Cell Biol Date: 2010-09-29 Impact factor: 5.085
Authors: V P Torchilin; T S Levchenko; A N Lukyanov; B A Khaw; A L Klibanov; R Rammohan; G P Samokhin; K R Whiteman Journal: Biochim Biophys Acta Date: 2001-04-02