TAT Peptide-Modified Liposomes Provide Enhanced Gene Delivery to Intracranial Human Brain Tumor Xenografts in Nude Mice
Abstract:In this study, we have investigated the potential of trans-activating transcriptional activator peptide (TATp)-modified liposomes to enhance the delivery of the model gene, plasmid encoding for the green fluorescent protein (pEGFP-N1), to human brain tumor U-87 MG cells in vitro and in an intracranial model in nude mice. The TATp-lipoplexes were characterized at lipid/DNA (+/−) charge ratios of 0.2, 5, 10, and 20 for size analysis and DNA complexation. The size distribution of DNA-loaded TATp-liposomes was narrow and the DNA complexation was firm at lipid/DNA (+/−) charge ratios of 5 and higher. TATp-lipoplexes had demonstrated an enhanced delivery of pEGFP-N1 to U-87 MG tumor cells in vitro at lipid/DNA (+/−) charge ratios of 5 and 10. In vivo transfection of intracranial brain tumors by intratumoral injections of TATp-lipoplexes showed an enhanced delivery of pEGFP-N1 selectively to tumor cells and subsequent effective transfection compared to plain plasmid-loaded lipoplexes. No transfection (green fluorescence of the GFP) was noted in the normal brain adjacent to tumor.
Document Type: Research Article
Affiliations: Department of Pharmaceutical Sciences and Center for Pharmaceutical Biotechnology and Nanomedicine, Northeastern University, Boston, MA 02115, USA
Publication date: August 1, 2006
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