Selection of DNA aptamers against glioblastoma cells with high affinity and specificity.
BACKGROUND
Glioblastoma is the most common and most lethal form of brain tumor in human. Unfortunately, there is still no effective therapy to this fatal disease and the median survival is generally less than one year from the time of diagnosis. Discovery of ligands that can bind specifically to this type of tumor cells will be of great significance to develop early molecular imaging, targeted delivery and guided surgery methods to battle this type of brain tumor.


RESULTS
We discovered two target-specific aptamers named GBM128 and GBM131 against cultured human glioblastoma cell line U118-MG after 30 rounds selection by a method called cell-based Systematic Evolution of Ligands by EXponential enrichment (cell-SELEX). These two aptamers have high affinity and specificity against target glioblastoma cells. They neither recognize normal astraglial cells, nor do they recognize other normal and cancer cell lines tested. Clinical tissues were also tested and the results showed that these two aptamers can bind to different clinical glioma tissues but not normal brain tissues. More importantly, binding affinity and selectivity of these two aptamers were retained in complicated biological environment.


CONCLUSIONS
The selected aptamers could be used to identify specific glioblastoma biomarkers. Methods of molecular imaging, targeted drug delivery, ligand guided surgery can be further developed based on these ligands for early detection, targeted therapy, and guided surgery of glioblastoma leading to effective treatment of glioblastoma.
Department of Neurosurgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China. kdz99988@sina.com
Dezhi
D
Kang
Jiangjie
J
Wang
Weiyun
W
Zhang
Yanling
Y
Song
Xilan
X
Li
Yuan
Y
Zou
Mingtao
M
Zhu
Zhi
Z
Zhu
Fuyong
F
Chen
Chaoyong James
CJ
Yang
D052157:Aptamers, Nucleotide / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D001254:Astrocytoma / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D001483:Base Sequence; D001667:Binding, Competitive; D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology; D002232:Carbocyanines / Q000737:chemistry / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D005434:Flow Cytometry; D005909:Glioblastoma / Q000378:metabolism / Q000473:pathology; D057809:HEK293 Cells; D019073:HT29 Cells; D006367:HeLa Cells; D006801:Humans; D061986:MCF-7 Cells; D018613:Microscopy, Confocal; D008969:Molecular Sequence Data; D009837:Oligodendroglioma / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D052156:SELEX Aptamer Technique / Q000379:methods*
D052157:Aptamers, Nucleotide; D002232:Carbocyanines; C085321:cyanine dye 5