title: Targeting of Micelles and Liposomes Loaded with the Pro-Apoptotic Drug, NCL-240, into NCI/ADR-RES Cells in a 3D Spheroid Model.
abstract: To develop transferrin (Tf)-targeted delivery systems for the pro-apoptotic drug, NCL-240, and to evaluate the efficacy of this delivery system in ovarian cancer NCI/ADR-RES cells, grown in vitro in a 3D spheroid model.
  
  
  
  Tf-targeted PEG-PE-based micellar and ePC/CHOL-based liposomal delivery systems for NCL-240 were prepared. NCI/ADR-RES cells were used to generate spheroids by a non-adhesive liquid overlay technique. Spheroid growth and development were monitored by size (diameter) analysis and H&E staining. The targeted formulations were compared to untargeted ones in terms of their degree of spheroid association and penetration. A cell viability analysis with NCL-240-loaded micelles and liposomes was performed to assess the effectiveness of Tf-targeting.
  
  
  
  Tf-targeted polymeric micelles and Tf-targeted liposomes loaded with NCL-240 were prepared. NCI/ADR-RES cells generated spheroids that demonstrated the presence of a distinct necrotic core along with proliferating cells in the spheroid periphery, partly mimicking in vivo tumors. The Tf-targeted micelles and liposomes had a deeper spheroid penetration as compared to the untargeted delivery systems. Cell viability studies using the spheroid model demonstrated that Tf-mediated targeting markedly improved the cytotoxicity profile of NCL-240.
  
  
  
  Transferrin targeting enhanced delivery and effectiveness of micelles and liposomes loaded with NCL-240 against NCI/ADR-RES cancer cells in a 3D spheroid model.
authors.affiliation: Department of Pharmaceutical Sciences, Center for Pharmaceutical Biotechnology and Nanomedicine, Northeastern University, 140 The Fenway, Room 236, 360 Huntington Avenue, Boston, Massachusetts, 02115, USA.
authors.forename: Bhushan S
authors.initials: BS
authors.lastname: Pattni
authors.affiliation: Department of Pharmaceutical Sciences, Center for Pharmaceutical Biotechnology and Nanomedicine, Northeastern University, 140 The Fenway, Room 236, 360 Huntington Avenue, Boston, Massachusetts, 02115, USA.
authors.forename: Srikar G
authors.initials: SG
authors.lastname: Nagelli
authors.affiliation: Department of Pharmaceutical Sciences, Center for Pharmaceutical Biotechnology and Nanomedicine, Northeastern University, 140 The Fenway, Room 236, 360 Huntington Avenue, Boston, Massachusetts, 02115, USA.
authors.forename: Bhawani
authors.initials: B
authors.lastname: Aryasomayajula
authors.affiliation: Department of Pharmaceutical Sciences, Center for Pharmaceutical Biotechnology and Nanomedicine, Northeastern University, 140 The Fenway, Room 236, 360 Huntington Avenue, Boston, Massachusetts, 02115, USA.
authors.forename: Pranali P
authors.initials: PP
authors.lastname: Deshpande
authors.affiliation: Department of Pharmaceutical Sciences, Center for Pharmaceutical Biotechnology and Nanomedicine, Northeastern University, 140 The Fenway, Room 236, 360 Huntington Avenue, Boston, Massachusetts, 02115, USA.
authors.forename: Abhijit
authors.initials: A
authors.lastname: Kulkarni
authors.affiliation: Department of Pharmaceutical Sciences, Center for Pharmaceutical Biotechnology and Nanomedicine, Northeastern University, 140 The Fenway, Room 236, 360 Huntington Avenue, Boston, Massachusetts, 02115, USA.
authors.forename: William C
authors.initials: WC
authors.lastname: Hartner
authors.affiliation: Department of Pharmaceutical Sciences, Center for Pharmaceutical Biotechnology and Nanomedicine, Northeastern University, 140 The Fenway, Room 236, 360 Huntington Avenue, Boston, Massachusetts, 02115, USA.
authors.forename: Ganesh
authors.initials: G
authors.lastname: Thakur
authors.affiliation: Department of Biochemistry, Tufts University School of Medicine, Boston, Massachusetts, USA.
authors.forename: Alexei
authors.initials: A
authors.lastname: Degterev
authors.affiliation: Department of Pharmaceutical Sciences, Center for Pharmaceutical Biotechnology and Nanomedicine, Northeastern University, 140 The Fenway, Room 236, 360 Huntington Avenue, Boston, Massachusetts, 02115, USA. v.torchilin@neu.edu.|Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah, 21589, Saudi Arabia. v.torchilin@neu.edu.
authors.forename: Vladimir P
authors.initials: VP
authors.lastname: Torchilin
mesh_terms: D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D045744:Cell Line, Tumor; D002733:Chlorophenols / Q000008:administration & dosage* / Q000378:metabolism; D016503:Drug Delivery Systems / Q000379:methods*; D005260:Female; D006801:Humans; D008081:Liposomes; D008823:Micelles; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000378:metabolism; D011355:Prodrugs / Q000008:administration & dosage* / Q000378:metabolism; D014168:Transferrin / Q000008:administration & dosage / Q000378:metabolism; D014230:Triazoles / Q000008:administration & dosage* / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D002733:Chlorophenols; D008081:Liposomes; D008823:Micelles; C000611383:NCL-240; D011355:Prodrugs; D014168:Transferrin; D014230:Triazoles
keywords: NCL-240; cancer spheroids; liposomes; micelles; transferrin-targeted drug delivery