Journal
JOURNAL OF DRUG TARGETING
Volume 15, Issue 7-8, Pages 538-545Publisher
TAYLOR & FRANCIS LTD
DOI: 10.1080/10611860701498203
Keywords
pharmaceutical nanocarriers; liposomes; pH-sensitive PEG-PE conjugates; green fluorescent protein; in vivo transfection; cancer cells
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Funding
- NATIONAL CANCER INSTITUTE [R01CA121838] Funding Source: NIH RePORTER
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R01HL055519] Funding Source: NIH RePORTER
- NCI NIH HHS [R01 CA121838] Funding Source: Medline
- NHLBI NIH HHS [R01 HL55519, R01 HL055519] Funding Source: Medline
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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 nonpH-sensitive bonds. The pGFP-loaded liposomal preparations have been administered intraturnorarly in tumor-bearing mice and the efficacy of tumor cell transfection was followed after 72 h. The administration of pGFP-TATp-liposomes with nonpH-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 intraturnoral 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.
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