Abstract

Nanopharmaceuticals Approaches with Locked Nucleic Acid Aptamers in Cancer

Jagat Kanwar, Professor, Deakin University

Drug resistance is a common drawback for most chemotherapeutic drugs and it promotes cancer survival and recurrence. The major protein that help a cell acquire MDR is P-glycoprotein (P-gp) and studies have showed that P-gp expression has been directly related to the degree of drug resistance in cells. P-gp also known as ABCB1 acts as a membranous molecular pump that effectively effluxes the chemotherapeutic drugs from within the cells. Overexpression of survivin in cancer cells has also been related to cause resistance to various chemotherapeutic compounds and therapies inhibiting survivin expression have shown sensitization of human cancer cells to various chemotherapeutic drugs such as docetaxel, paclitaxel and bortezomib. Studies have also shown that CD133 positive cancer stem cells resist chemotherapy which is mainly due to higher expression of inhibitors of apoptosis protein (IAP) families and it has been also observed that the colony formation of CD133 positive cells is quite higher when compared to CD133 negative cells mainly due to overexpression of survivin. A major area of interest has come up using biomolecules which focusses on specifically target the diseased tissues. In our previous studies we have shown chimeric form of Fe-bLf (LNA-Nucleolin+EpCAM aptamer)-spions showed high specificity towards the tumour both in vitro and in vivo. In another study using ceramic polymer nanocarriers (ACSC NCs) we have shown that Fe-bLF(LNA-EpCAM aptamer+LNAsiRNA(survivin))-ACSC NCs were highly specific to tumour when compared to any other parts of the mice and the nanocarriers led to significant cytotoxicity specifically in tumour cells without harming the primary cells. We have also used novel oligo LNA siRNA (survivin) to target the nanocarriers and inhibit survivin expression in drug resistant cancer stem cells.