Radiosensitization of breast cancer cells using AS1411 aptamer-conjugated gold nanoparticles

Introduction: A main choice for cancer treatment is radiotherapy. But, the radiotherapy disadvantage is damages caused by radiation given to normal tissues/organs surrounding cancer. One way to avoid this is via increasing radiosensitization of cancer cells. Gold nanoparticles (GNPs) have shown sensitizing effect on cancer cells by enhancing their absorbed dose. Unlike earlier delivery techniques developed for nanotherapeutics, active targeting can achieve specific effect and higher uptake of GNPs in tumors while leave healthy cells untouched and consequently improve the therapeutic index. To achieve active targeting, GNPs should be equipped with functional ligands which can recognize and adhere to the receptors of cancer cells. Aptamers are small DNA-molecule/RNA-fragments with high specificity and affinity towards target molecules. AS1411 aptamer can specifically bind to over-expressed nucleolin on the membrane of tumor cells including breast cancer. This aptamer is capable to enter cancer cells through specific ligand–receptor interaction. Greater uptake of GNPs by cells may induce increased radiation effects. Cancer stem cells are a small population of cells within a tumor capable for self-renewal and differentiation into various cell types. Materials and Methods: We hypothesized that conjugation of GNPs with AS1411 (AS1411/GNPs) could increase GNPs-mediated radiosensitization in breast cancer cells. We hypothesized that AS1411/GNPs would radiosensitize breast cancer stem/progenitor cells grown to three- dimensional (3D) mammospheres. Cytotoxicity studies of the GNPs and AS1411/GNPs were done on two different cancer cell lines of MCF-7 and MDA-MB-231 with MTT assay. Atomic absorption spectroscopy (AAS) confirmed the cellular uptake of particles. Radiosensitizing effect of GNPs and AS1411/GNPs on MDA-MB 231 and MCF- 7 cells assessed by clonogenic assay. Results: Clonogenic survival data revealed that AS1411/GNPs at 12.5 mg/L results in radiosensitization of breast cancer cells. Mammosphere of MCF-7 was more resistant than their monolayer counterparts. Conclusion: The combination of the sensitizing GNPs with the AS14411 aptamer can be regarded for improved treatment of breast cancer cells especially for the mammosphere MCF-7 cancer cells mimicking cancerous tumors.