caa a22 4500 445314117 CHVBK 20180317142640.0 cr unu---uuuuu 170323e20110201xx s 000 0 eng 10.1007/s11095-010-0242-3 doi (NATIONALLICENCE)springer-10.1007/s11095-010-0242-3 Palmitoyl Ascorbate-Loaded Polymeric Micelles: Cancer Cell Targeting and Cytotoxicity [Elektronische Daten] [Rupa Sawant, Onkar Vaze, Gerard D'Souza, Karen Rockwell, Vladimir Torchilin] ABSTRACT: Purpose: To evaluate the potential of palmitoyl ascorbate (PA)-loaded micelles for ascorbate-mediated cancer cell targeting and cytotoxicity. Methods: PA was incorporated in polyethylene glycol-phosphatidyl ethanolamine micelles at varying concentrations. The formulations were evaluated for PA content by RP-HPLC. A stable formulation was selected based on size and zeta potential measurements. A co-culture of cancer cells and GFP-expressing non-cancer cells was used to determine the specificity of PA micelle binding. In vitro cytotoxicity of the micellar formulations towards various cancer cell lines was investigated using a cell viability assay. To elucidate the mechanism of action of cell death in vitro, the effect of various H2O2 scavengers and metal chelators on PA-mediated cytotoxicity was studied. The in vivo anti-cancer activity of PA micelles was studied in female Balb/c mice bearing a murine mammary carcinoma (4T1 cells). Results: PA micelles associated preferentially with various cancer cells compared to non-cancer cells in co-culture. PA micelles exhibited anti-cancer activity in cancer cell lines both in vitro and in vivo. The mechanism of cell death was due primarily to generation of reactive oxygen species (ROS). Conclusions: The anti-cancer activity of PA micelles associated with its enhanced cancer cell binding and subsequent generation of ROS. Springer Science+Business Media, LLC, 2010 cancer nationallicence micelles nationallicence nanocarriers nationallicence palmitoyl ascorbate nationallicence targeting nationallicence Sawant Rupa Department of Pharmaceutical Sciences and Center for Pharmaceutical Biotechnology and Nanomedicine, Northeastern University, Mugar Building, Room 312, 360 Huntington Avenue, 02115, Boston, Massachusetts, USA aut Vaze Onkar Department of Pharmaceutical Sciences and Center for Pharmaceutical Biotechnology and Nanomedicine, Northeastern University, Mugar Building, Room 312, 360 Huntington Avenue, 02115, Boston, Massachusetts, USA aut D'Souza Gerard Department of Pharmaceutical Sciences and Center for Pharmaceutical Biotechnology and Nanomedicine, Northeastern University, Mugar Building, Room 312, 360 Huntington Avenue, 02115, Boston, Massachusetts, USA aut Rockwell Karen Department of Pharmaceutical Sciences and Center for Pharmaceutical Biotechnology and Nanomedicine, Northeastern University, Mugar Building, Room 312, 360 Huntington Avenue, 02115, Boston, Massachusetts, USA aut Torchilin Vladimir Department of Pharmaceutical Sciences and Center for Pharmaceutical Biotechnology and Nanomedicine, Northeastern University, Mugar Building, Room 312, 360 Huntington Avenue, 02115, Boston, Massachusetts, USA aut Pharmaceutical Research Springer US; http://www.springer-ny.com 28/2(2011-02-01), 301-308 0724-8741 28:2<301 2011 28 11095 https://doi.org/10.1007/s11095-010-0242-3 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s11095-010-0242-3 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Sawant Rupa Department of Pharmaceutical Sciences and Center for Pharmaceutical Biotechnology and Nanomedicine, Northeastern University, Mugar Building, Room 312, 360 Huntington Avenue, 02115, Boston, Massachusetts, USA aut NATIONALLICENCE 700 1- Vaze Onkar Department of Pharmaceutical Sciences and Center for Pharmaceutical Biotechnology and Nanomedicine, Northeastern University, Mugar Building, Room 312, 360 Huntington Avenue, 02115, Boston, Massachusetts, USA aut NATIONALLICENCE 700 1- D'Souza Gerard Department of Pharmaceutical Sciences and Center for Pharmaceutical Biotechnology and Nanomedicine, Northeastern University, Mugar Building, Room 312, 360 Huntington Avenue, 02115, Boston, Massachusetts, USA aut NATIONALLICENCE 700 1- Rockwell Karen Department of Pharmaceutical Sciences and Center for Pharmaceutical Biotechnology and Nanomedicine, Northeastern University, Mugar Building, Room 312, 360 Huntington Avenue, 02115, Boston, Massachusetts, USA aut NATIONALLICENCE 700 1- Torchilin Vladimir Department of Pharmaceutical Sciences and Center for Pharmaceutical Biotechnology and Nanomedicine, Northeastern University, Mugar Building, Room 312, 360 Huntington Avenue, 02115, Boston, Massachusetts, USA aut NATIONALLICENCE 773 0- Pharmaceutical Research Springer US; http://www.springer-ny.com 28/2(2011-02-01), 301-308 0724-8741 28:2<301 2011 28 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer