title: Paclitaxel-loaded PEG-PE-based micellar nanopreparations targeted with tumor-specific landscape phage fusion protein enhance apoptosis and efficiently reduce tumors.
abstract: In an effort to improve the therapeutic index of cancer chemotherapy, we developed an advanced nanopreparation based on the combination of landscape phage display to obtain new targeting ligands with micellar nanoparticles for tumor targeting of water-insoluble neoplastic agents. With paclitaxel as a drug, this self-assembled nanopreparation composed of MCF-7-specific phage protein and polyethylene glycol-phosphatidylethanolamine (PEG-PE) micelles showed selective toxicity to target cancer cells rather than nontarget, non cancer cells in vitro. In vivo, the targeted phage micelles triggered a dramatic tumor reduction and extensive necrosis as a result of improved tumor delivery of paclitaxel. The enhanced anticancer effect was also verified by an enhanced apoptosis and reduced tumor cell proliferation following the treatment with the targeted micellar paclitaxel both in vitro and in vivo. The absence of hepatotoxicity and pathologic changes in tissue sections of vital organs, together with maintenance of overall health of mice following the treatment, further support its translational potential as an effective and safe chemotherapy for improved breast cancer treatment.
authors.affiliation: Center for Pharmaceutical Biotechnology and Nanomedicine, Northeastern University, Boston, Massachusetts.
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
authors.forename: Shenghong
authors.initials: S
authors.lastname: Yang
authors.affiliation: Center for Pharmaceutical Biotechnology and Nanomedicine, Northeastern University, Boston, Massachusetts.
authors.forename: Leslie A
authors.initials: LA
authors.lastname: Mei
authors.affiliation: Center for Pharmaceutical Biotechnology and Nanomedicine, Northeastern University, Boston, Massachusetts.
authors.forename: Chirag K
authors.initials: CK
authors.lastname: Parmar
authors.affiliation: Department of Pathobiology, Auburn University, Alabama.
authors.forename: James W
authors.initials: JW
authors.lastname: Gillespie
authors.affiliation: Center for Translational Imaging, Northeastern University, Boston, Massachusetts.
authors.forename: Kulkarni P
authors.initials: KP
authors.lastname: Praveen
authors.affiliation: Department of Pathobiology, Auburn University, Alabama.
authors.forename: Valery A
authors.initials: VA
authors.lastname: Petrenko
authors.affiliation: Center for Pharmaceutical Biotechnology and Nanomedicine, Northeastern University, Boston, Massachusetts. King Abdulaziz University, Abdullah Sulayman, Jeddah, Saudi Arabia. v.torchilin@neu.edu.
authors.forename: Vladimir P
authors.initials: VP
authors.lastname: Torchilin
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D016503:Drug Delivery Systems; D005260:Female; D006801:Humans; D051379:Mice; D008823:Micelles; D053758:Nanoparticles; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D017239:Paclitaxel / Q000008:administration & dosage*; D010714:Phosphatidylethanolamines; D011092:Polyethylene Glycols; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D008823:Micelles; D010714:Phosphatidylethanolamines; C067972:dioleoyl-N-(monomethoxypolyethylene glycol succinyl)phosphatidylethanolamine; D011092:Polyethylene Glycols; D017239:Paclitaxel