Palmitoyl ascorbate-loaded polymeric micelles: cancer cell targeting and cytotoxicity.
OBJECTIVE
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 H(2)O(2) 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.
Sawant
Rupa R
RR
Department of Pharmaceutical Sciences and Center for Pharmaceutical Biotechnology and Nanomedicine, Northeastern University, Mugar Building, 360 Huntington Avenue, Boston, Massachusetts 02115, USA.
Vaze
Onkar
O
D'Souza
Gerard G M
GG
Rockwell
Karen
K
Torchilin
Vladimir P
VP
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D001205:Ascorbic Acid / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002614:Chelating Agents / Q000378:metabolism; D018920:Coculture Techniques; D004337:Drug Carriers / Q000737:chemistry; D005260:Female; D016166:Free Radical Scavengers / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000737:chemistry; D020128:Inhibitory Concentration 50; D051379:Mice; D008807:Mice, Inbred BALB C; D008823:Micelles; D023421:Models, Animal; D041681:NIH 3T3 Cells; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000473:pathology; D010714:Phosphatidylethanolamines / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D017382:Reactive Oxygen Species; D012235:Rhodamines / Q000737:chemistry*
C519184:1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-methoxy-poly(ethylene glycol 2000); D000970:Antineoplastic Agents; D002614:Chelating Agents; D004337:Drug Carriers; D016166:Free Radical Scavengers; D008823:Micelles; D010714:Phosphatidylethanolamines; D017382:Reactive Oxygen Species; D012235:Rhodamines; C055952:N-(lissamine-rhodamine B sulfonyl)-1,2-dipalmitoylphosphatidylethanolamine; D011092:Polyethylene Glycols; D006861:Hydrogen Peroxide; D001205:Ascorbic Acid