PMID- 19446767 OWN - NLM STAT- MEDLINE DCOM- 20090804 LR - 20211020 IS - 1873-3476 (Electronic) IS - 0378-5173 (Print) IS - 0378-5173 (Linking) VI - 374 IP - 1-2 DP - 2009 Jun 5 TI - Enhanced cytotoxicity of TATp-bearing paclitaxel-loaded micelles in vitro and in vivo. PG - 114-8 LID - 10.1016/j.ijpharm.2009.02.022 [doi] AB - 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. FAU - Sawant, Rupa R AU - Sawant RR AD - Department of Pharmaceutical Sciences and Center for Pharmaceutical Biotechnology and Nanomedicine, Northeastern University, 360 Huntington Avenue, Boston, MA 02115, USA. FAU - Torchilin, Vladimir P AU - Torchilin VP LA - eng GR - R01 EB001961/EB/NIBIB NIH HHS/United States GR - R01 EB 001961/EB/NIBIB NIH HHS/United States GR - R01 CA121838/CA/NCI NIH HHS/United States GR - R01 EB001961-09/EB/NIBIB NIH HHS/United States GR - R01 CA 121838/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20090327 PL - Netherlands TA - Int J Pharm JT - International journal of pharmaceutics JID - 7804127 RN - 0 (Antineoplastic Agents, Phytogenic) RN - 0 (Drug Carriers) RN - 0 (Gene Products, tat) RN - 0 (Micelles) RN - 0 (Phosphatidylethanolamines) RN - 39382-08-6 (phosphatidylethanolamine) RN - 3WJQ0SDW1A (Polyethylene Glycols) RN - P88XT4IS4D (Paclitaxel) SB - IM MH - Animals MH - Antineoplastic Agents, Phytogenic/*administration & dosage MH - Apoptosis/drug effects MH - Cell Line, Tumor MH - Drug Carriers/chemistry MH - Female MH - Gene Products, tat/*chemistry MH - Humans MH - In Situ Nick-End Labeling MH - Mammary Neoplasms, Experimental/*drug therapy MH - Mice MH - Mice, Inbred BALB C MH - Micelles MH - Paclitaxel/*administration & dosage MH - Phosphatidylethanolamines/chemistry MH - Polyethylene Glycols/chemistry PMC - PMC2684523 MID - NIHMS105835 EDAT- 2009/05/19 09:00 MHDA- 2009/08/06 09:00 PMCR- 2010/06/05 CRDT- 2009/05/19 09:00 PHST- 2009/01/28 00:00 [received] PHST- 2009/02/28 00:00 [accepted] PHST- 2009/05/19 09:00 [entrez] PHST- 2009/05/19 09:00 [pubmed] PHST- 2009/08/06 09:00 [medline] PHST- 2010/06/05 00:00 [pmc-release] AID - S0378-5173(09)00128-8 [pii] AID - 10.1016/j.ijpharm.2009.02.022 [doi] PST - ppublish SO - Int J Pharm. 2009 Jun 5;374(1-2):114-8. doi: 10.1016/j.ijpharm.2009.02.022. Epub 2009 Mar 27.