Enhanced cytotoxicity of TATp-bearing paclitaxel-loaded micelles in vitro and in vivo.
Cell-penetrating peptide (TATp) was attached to the distal tips of polyethyleneglycol (PEG) moieties of polyethyleneglycol-phosphatidylethanolamine (PEG-PE) micelles loaded with paclitaxel (PCT). The TATp-modified micelles demonstrated an increased interaction with cancer cells compared to non-modified micelles resulting in a significant increase of the in vitro cytotoxicity to different cancer cells. TATp-modified PCT-loaded micelles were administered intratumorally in mice and the induction of apoptosis in tumor cells was studied after 48h with the Terminal Deoxynucleotidyl Transferase Biotin-dUTP Nick End Labeling (TUNEL) assay using free PCT and TATp-free PCT-loaded PEG-PE micelles as controls. A significant apoptotic cell death was observed in tumors treated with PCT-loaded micelles modified with TATp, while the treatment with free PCT or with non-modified PCT-loaded micelles resulted in much smaller number of TUNEL-positive cells within tumors.
Sawant
Rupa R
RR
Department of Pharmaceutical Sciences and Center for Pharmaceutical Biotechnology and Nanomedicine, Northeastern University, 360 Huntington Avenue, Boston, MA 02115, USA.
Torchilin
Vladimir P
VP
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D004337:Drug Carriers / Q000737:chemistry; D005260:Female; D015696:Gene Products, tat / Q000737:chemistry*; D006801:Humans; D020287:In Situ Nick-End Labeling; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D008823:Micelles; D017239:Paclitaxel / Q000008:administration & dosage*; D010714:Phosphatidylethanolamines / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry
D000972:Antineoplastic Agents, Phytogenic; D004337:Drug Carriers; D015696:Gene Products, tat; D008823:Micelles; D010714:Phosphatidylethanolamines; C483858:phosphatidylethanolamine; D011092:Polyethylene Glycols; D017239:Paclitaxel