Doxorubicin is a well-known chemotherapy medication for cancer treatments. The toxic effects of doxorubicin can lead to nausea, hair loss, darkening of skin and cause serious side effects of dilated cardiomyopathy and typhlitis. [1] We stored the chemical in tightly-closed container within a designated area in the refrigerator away from heat, light and oxidising agents. We handled the chemical in our experiments with gloves and cleaned and disposed the waste with care to prevent contamination.
Safety in Design
Usually doxorubicin is injected into patient’s vein to circulate in blood and reach the tumour sites. The leakage of drug outside of the vein can result in tissue damage. [2] The Nano Drug carrier we designed are loaded with doxorubicin by intercalation. The stable nontoxic DNA tetrahedron protects and delivers the drug to cancer cells to better control the release of drug upon strand displacement by the miRNA targets in breast cancer cells. From interviews with Dr Lau (a molecular pathologist from Hong Kong Yan Chai Hospital) and Dr Beijersbergen (Netherlands Cancer Institute) who gave us advice on further enhancement of the specificity of our nano device in drug delivery, we revised our design with incorporation of AS1411, an DNA aptamer against nucleloin which has an overexpression level in breast cancer cells. This advancement aims at higher efficient targeting and entry into cells so to reduce any side effects on normal cells.
Dr Berkhout reminded us the importance of careful considerations over possible off-target consequences. WE then evaluated our Nano Drug Carrier's intrinsic toxicity and extracellular stability in experiments. Though theoretically DNA is a safe and biodegradable, we are interested in how 3D nanostructures may act inside the body.
References
O’Brien, M. E. R., Wigler, N., Inbar, M., Rosso, R., Grischke, E., Santoro, A....Tendler, C. (2004, March 01). Reduced cardiotoxicity and comparable efficacy in a phase III trial of pegylated liposomal doxorubicin HCl (CAELYX™/Doxil®) versus conventional doxorubicin for first-line treatment of metastatic breast cancer. Annals of Oncology, 15(3), 440–449.
Gault, D.T. (1993). Extravasation injuries. British Journal of Plastic Surgery, 46(2), 91-96.
