Enhanced transfection of tumor cells in vivo using "Smart" pH-sensitive TAT-modified pegylated liposomes.

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.

journal_name

J Drug Target

authors

Kale AA,Torchilin VP

doi

10.1080/10611860701498203

subject

Has Abstract

pub_date

2007-08-01 00:00:00

pages

538-45

issue

7-8

eissn

1061-186X

issn

1029-2330

pii

780334291

journal_volume

15

pub_type

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