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.
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