title: Transferrin-targeted polymeric micelles co-loaded with curcumin and paclitaxel: efficient killing of paclitaxel-resistant cancer cells.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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: Department of Pharmaceutical Sciences Center for Pharmaceutical Biotechnology and Nanomedicine, Northeastern University, 140 The Fenway, Room 236, 360 Huntington Ave., Boston, Massachusetts, 02115, USA.
authors: Abraham H
authors: AH
authors: Abouzeid
authors: Niravkumar R
authors: NR
authors: Patel
authors: Can
authors: C
authors: Sarisozen
authors: Vladimir P
authors: VP
authors: Torchilin
mesh_terms: D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D003474:Curcumin / Q000008:administration & dosage* / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems / Q000379:methods*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects* / Q000502:physiology; D005260:Female; D006801:Humans; D008823:Micelles; D010051:Ovarian Neoplasms; D017239:Paclitaxel / Q000008:administration & dosage* / Q000737:chemistry; D011108:Polymers / Q000008:administration & dosage / Q000737:chemistry; D014168:Transferrin / Q000008:administration & dosage* / Q000737:chemistry
chemical_list: D008823:Micelles; D011108:Polymers; D014168:Transferrin; D003474:Curcumin; D017239:Paclitaxel