OP16 SELECTIVE TARGETING OF GLIOMA WITH NUCLEIC ACID APTAMERS

INTRODUCTION: Targeted drug delivery via aptamers may reduce non-specific toxicity of chemotherapy by selectively directing anti-cancer drugs to tumour cells. The study aimed to examine the binding selectivity of DNA aptamers on glial cell lines and primary glioma tissues. METHOD: Aptamers SA44DNA and SA43DNA tagged with Cy3 fluorescent dye were screened on cell lines and analysed through confocal microscopy and flow cytometry. Primary tissues from glioma patients: grade I(n = 7), grade II(n = 14), grade III(n = 10), grade IV(n = 10) and non-cancerous brain(n = 12) were screened with biotin labelled aptamers and quantified using an established IHC scoring system. Fisher's exact test was performed whereby tissue sections with a total score above 3 were considered positive. RESULTS: Aptamers SA44DNA and SA43DNA showed higher uptake in U87MG and 1321N1 glioma cell lines compared to non-cancerous SVGp12 cells as measured by confocal microscopy. The data was confirmed by flow cytometry analysis where MFI was significantly higher (p < 0.05) in U87MG and 1321N1 compared to non-cancerous SVGp12 cells. The binding assay showed SA44 DNA (Kd,21.11 plus or minus 3.30 nM) and SA43 DNA (Kd,21.56 plus or minus 4.60 nM) bound with strong affinity to the target U87MG cells. Immunohistochemistry staining on primary tissues revealed that SA44 DNA had no significant binding selectivity between all grades of glioma and non-cancerous tissues (p > 0.05), however, SA43 DNA showed significant binding selectivity towards grade I(p = 0.0063), grade II(p = 0.0511), grade III(p = 0.0019) and IV(p = 0.0083) compared to non-cancerous brain tissues using Fisher's exact test. CONCLUSION: The data have shown promising results for the application of the DNA aptamers for specific targeting of glioma.