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. 2009 Jun 5;374(1-2):114-8.
doi: 10.1016/j.ijpharm.2009.02.022. Epub 2009 Mar 27.

Enhanced cytotoxicity of TATp-bearing paclitaxel-loaded micelles in vitro and in vivo

Rupa R Sawant  1 , Vladimir P Torchilin
Affiliations

Enhanced cytotoxicity of TATp-bearing paclitaxel-loaded micelles in vitro and in vivo

Rupa R Sawant et al. Int J Pharm. .

Abstract

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.

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Figures

Figure 1
Figure 1
Schematic representation of the micelles used in this study.
Figure 2
Figure 2
Left panel shows the bright field and right panel shows the fluorescent microscopy of 4T1 cells treated with Rh-PE:PEG750-PE micelles (A), Rh-PE: PEG750-PE: TATp-PEG1000-PE micelles. Magnification ×40 objective.
Figure 3
Figure 3. In vitro
cytotoxicity of various PCT formulations towards 4T1 and MCF-7 cells.
Figure 4
Figure 4
Detection of the apoptotic cells by the fluorescence microscopy in frozen tumor sections. Apoptosis determined by TUNEL. The left panel shows the sections stained with DAPI and the right panel shows TUNEL. Negative control (A), free PCT (B), PCT-loaded micelles without TATp (C), PCT-loaded micelles with TATp (D). Magnification ×20 objective.
See this image and copyright information in PMC

References

    1. Astriab-Fisher A, Sergueev D, Fisher M, Shaw BR, Juliano RL. Conjugates of antisense oligonucleotides with the Tat and antennapedia cell-penetrating peptides: effects on cellular uptake, binding to target sequences, and biologic actions. Pharm Res. 2002;19:744–754. - PubMed
    1. Bae Y, Kataoka K. Significant enhancement of antitumor activity and bioavailability of intracellular pH-sensitive polymeric micelles by folate conjugation. J Control Release. 2006;116:e49–50. - PubMed
    1. Fretz MM, Koning GA, Mastrobattista E, Jiskoot W, Storm G. OVCAR-3 cells internalize TAT-peptide modified liposomes by endocytosis. Biochim Biophys Acta. 2004;1665:48–56. - PubMed
    1. Fujita T, Furuhata M, Hattori Y, Kawakami H, Toma K, Maitani Y. High gene delivery in tumor by intratumoral injection of tetraarginine-PEG lipid-coated protamine/DNA. J Control Release. 2008;129:124–127. - PubMed
    1. Gold R, Schmied M, Giegerich G, Breitschopf H, Hartung HP, Toyka KV, Lassmann H. Differentiation between cellular apoptosis and necrosis by the combined use of in situ tailing and nick translation techniques. Lab Invest. 1994;71:219–225. - PubMed

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