TAT peptide-modified liposomes provide enhanced gene delivery to intracranial human brain tumor xenografts in nude mice.
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.
Gupta
Bhawna
B
Department of Pharmaceutical Sciences and Center for Pharmaceutical Biotechnology and Nanomedicine, Northeastern University, Boston, MA 02115, USA.
Levchenko
Tatiana S
TS
Torchilin
Vladimir P
VP
D000818:Animals; D001254:Astrocytoma / Q000473:pathology / Q000628:therapy*; D001932:Brain Neoplasms / Q000473:pathology / Q000628:therapy*; D002540:Cerebral Cortex; D004247:DNA / Q000008:administration & dosage* / Q000235:genetics; D004333:Drug Administration Routes; D015696:Gene Products, tat / Q000008:administration & dosage*; D018014:Gene Transfer Techniques; D015756:Genes, tat / Q000235:genetics*; D015316:Genetic Therapy / Q000379:methods*; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D015552:Injections, Intralesional; D008081:Liposomes; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D014162:Transfection; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured; D015854:Up-Regulation; D023041:Xenograft Model Antitumor Assays
D015696:Gene Products, tat; D008081:Liposomes; D049452:Green Fluorescent Proteins; D004247:DNA