Enhanced cytotoxicity of TATp-bearing paclitaxel-loaded micellesin vitroandin vivo

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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 48 h 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.

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