OP16 * SELECTIVE TARGETING OF GLIOMA WITH NUCLEIC ACID APTAMERS

Abstract

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 ± 3.30 nM) and SA43 DNA (Kd,21.56 ± 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.