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Enhanced transfection of tumor cells in vivo using 'Smart' pH-sensitive TAT-modified pegylated liposomes.
| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Kale, Amit A. Torchilin, Vladimir P. |
| Description | Country affiliation: United States Author Affiliation: Kale AA ( Department of Pharmaceutical Sciences and Center for Pharmaceutical Biotechnology and Nanomedicine, Northeastern University, Boston, MA 02115, USA.) |
| Abstract | Liposomes have been prepared loaded with DNA (plasmid encoding for the green fluorescent protein, GFP) and additionally modified with TATp and PEG, with PEG being attached to the liposome surface via both pH-sensitive hydrazone and non-pH-sensitive bonds. The pGFP-loaded liposomal preparations have been administered intratumorarly in tumor-bearing mice and the efficacy of tumor cell transfection was followed after 72 h. The administration of pGFP-TATp-liposomes with non-pH-sensitive PEG coating has resulted in only minimal transfection of tumor cells because of steric hindrances for the liposome-to-cell interaction created by the PEG coat, which shielded the surface-attached TATp. At the same time, the administration of pGFP-TATp-liposomes with the low pH-detachable PEG resulted in at least three times more efficient transfection since the removal of PEG under the action of the decreased intratumoral pH leads to the exposure of the liposome-attached TATp residues, enhanced penetration of the liposomes inside tumor cells and more effective intracellular delivery of the pGFP. This result can be considered as an important step in the development of tumor-specific stimuli-sensitive drug and gene delivery systems. |
| File Format | HTM / HTML |
| ISSN | 1061186X |
| e-ISSN | 10292330 |
| Journal | Journal of Drug Targeting |
| Issue Number | 7-8 |
| Volume Number | 15 |
| Language | English |
| Publisher | Taylor & Francis |
| Publisher Date | 2007-08-01 |
| Publisher Place | Great Britain (UK) |
| Access Restriction | Open |
| Subject Keyword | Discipline Pharmacology Administration & Dosage Drug Delivery Systems Lung Neoplasms Therapy Transfection Animals Cell Line, Tumor Gene Products, Tat Chemistry Gene Transfer Techniques Green Fluorescent Proteins Hydrogen-ion Concentration Liposomes Luminescent Agents Mice Mice, Nude Permeability Plasmids Polyethylene Glycols Research Support, N.i.h., Extramural |
| Content Type | Text |
| Resource Type | Article |
| Subject | Pharmaceutical Science |