Selective targeting to glioma with nucleic acid aptamers

Aptekar, Shraddha Ashok (2015) Selective targeting to glioma with nucleic acid aptamers. Doctoral thesis, University of Central Lancashire.

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The term glioma encompasses brain tumours arising from the glial cells. Malignant glioma are characterised by a rapid growth rate and high capacity for invasive infiltration to surrounding brain tissue, hence diagnosis and treatment is difficult, and patient survival is poor. Aptamers are small molecular ligands composed of short oligonucleotides that bind to a target with high specificity and affinity. They are produced in vitro through a method called systematic evolution of ligands by exponential enrichment (SELEX).

The aim of the study was to examine the binding selectivity of DNA aptamers on commercial glial cell lines and primary glioma tissues. RNA aptamers and their DNA homologues (SA44, SA43, SA56) were selected for study which showed strong binding affinity to the target U87MG cells as measured by flow cytometry. SA44 and SA43 showed higher uptake and cytoplasmic localisation in U87MG and 1321N1 glioma cell lines compared to non-cancerous SVGP12 cells and non-glioma MCF-7 and T24 cells as measured by confocal microscopy. The data was confirmed quantitatively by flow cytometry analysis, which showed that the aptamers were able to actively internalise in U87MG and 1321N1 tumorigenic cells compared to the non-cancerous and non-glioma cell types. Histochemistry staining on paraffin embedded, formalin fixed patient tissues revealed that the binding selectivity was found to be significantly higher for only SA43 aptamer (p < 0.05) in glioma tissues (grade I, II, III and IV) compared to the non-cancerous and tissues. Aptamer SA43 also showed cell type selectivity within the tissue.

The results indicate that SA43 aptamer can differentiate between glioma and non-cancerous cells and tissues and therefore, show promise for histological diagnosis of glioma and targeted delivery. In the future, targeting tumour cells and tissues through the use of SA43 aptamer will help develop molecular imaging, targeted delivery by reduction of the non-specific toxicity of chemotherapy and selectively directing anti-cancer drugs to tumour cells.

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