Paclitaxel-loaded polymeric micelles modified with MCF-7 cell-specific phage protein: enhanced binding to target cancer cells and increased cytotoxicity.
Polymeric micelles are used as pharmaceutical carriers to increase solubility and bioavailability of poorly water-soluble drugs. Different ligands are used to prepare targeted polymeric micelles. Earlier, we developed the method for use of specific landscape phage fusion coat proteins as targeted delivery ligands and demonstrated the efficiency of this approach with doxorubicin-loaded PEGylated liposomes. Here, we describe a MCF-7 cell-specific micellar formulation self-assembled from the mixture of the micelle-forming amphiphilic polyethylene glycol-phosphatidylethanolamine (PEG-PE) conjugate, MCF-7-specific landscape phage fusion coat protein, and the hydrophobic drug paclitaxel. These micelles demonstrated a very low cmc value and specific binding to target cells. Using an in vitro coculture model, FACS analysis, and fluorescence microscopy we showed that MCF-7 targeted phage-micelles preferentially bound to target cells compared to nontarget cells. As a result, targeted paclitaxel-loaded phage-micelles demonstrated a significantly higher cytotoxicity toward target MCF-7 cells than free drug or nontargeted micelle formulations, but failed to show such a differential toxicity toward nontarget C166 cells. Overall, cancer cell-specific phage proteins identified from phage display peptide libraries can serve as targeting ligands ("substitute antibody") for polymeric micelle-based pharmaceutical preparations.
Center for Pharmaceutical Biotechnology and Nanomedicine, Northeastern University, Boston, Massachusetts 02115, USA.
Tao
T
Wang
Valery A
VA
Petrenko
Vladimir P
VP
Torchilin
D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry* / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008823:Micelles; D046529:Microscopy, Electron, Transmission; D008856:Microscopy, Fluorescence; D017239:Paclitaxel / Q000737:chemistry* / Q000494:pharmacology*; D010714:Phosphatidylethanolamines / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D011108:Polymers / Q000737:chemistry*
D000972:Antineoplastic Agents, Phytogenic; D008823:Micelles; D010714:Phosphatidylethanolamines; D011108:Polymers; C483858:phosphatidylethanolamine; D011092:Polyethylene Glycols; D017239:Paclitaxel