Identification and characterization of novel human glioma-specific peptides to potentiate tumor-specific gene delivery.
Glioblastomas account for approximately 20% of all primary brain tumors in adults. Glioblastoma multiforme (GBM) is a highly malignant tumor. In spite of advances in surgery, chemotherapy, and radiotherapy, the life expectancy of the patient with glioblastoma is approximately 11 months. To enhance glioma-specific gene delivery, we employed a 12-mer phage display peptide library to isolate phages that bind specifically to human glioma cell lines. Here, we report the isolation and functional characterization of novel glioma-specific peptides that target transgenes specifically to a wide array of human glioblastomas in vitro and in vivo. One of the isolated peptides, tentatively denoted as MG11, is demonstrated to be glioma specific and gives an in vitro-binding enrichment of more than 5-fold for glioma cells when compared with nonglioma cells. Intravenous injection of phages bearing the MG11 peptide-binding motif enables the phages to home specifically to glioma xenografts. Most significantly, when Lissamine rhodamine-labeled MG11 peptide is injected intratumorally, it targets specifically to glioma xenografts instead of non-glioma-derived xenografts. In summary, our results suggest that the MG11 peptide is able to target specifically to tumors of glial origin, which would allow the design of applications related to the diagnosis and treatment of human gliomas.
Ho
Ivy A W
IA
Division of Cellular and Molecular Research, Gene Vector Laboratory, National Cancer Centre, Singapore 169610.
Lam
Paula Y P
PY
Hui
Kam M
KM
D001435:Bacteriophages / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D005453:Fluorescence; D018390:Gene Targeting / Q000379:methods*; D015316:Genetic Therapy / Q000379:methods*; D005909:Glioblastoma / Q000628:therapy*; D006801:Humans; D008156:Luciferases; D021141:Nucleic Acid Amplification Techniques; D010455:Peptides / Q000235:genetics* / Q000378:metabolism; D012235:Rhodamines; D014162:Transfection; D019076:Transgenes / Q000235:genetics
D010455:Peptides; D012235:Rhodamines; C022027:lissamine rhodamine B; D008156:Luciferases