Insights into the biomedical effectsof carboxylated single-wall carbon nanotubeson telomerase and telomeres

摘要

Both human telomeric G-rich and C-rich DnA have been considered as specific drug targetsfor cancer therapy. However, due to i-motif structure instability and lack of specific bindingagents, it remains unclear whether stabilization of telomeric i-motif can inhibit telomeraseactivity. single-walled carbon nanotubes (sWnTs) have been reported as the first ligand thatcan selectively stabilize human telomeric i-motif DnA. Here we report that sWnTs can inhibittelomerase activity through stabilization of i-motif structure. The persistence of i-motif and theconcomitant G-quadruplex eventually leads to telomere uncapping and displaces telomerebinding proteins from telomere. The dysfunctional telomere triggers DnA damage responseand elicits upregulation of p16 and p21 proteins. This is the first example that sWnTs caninhibit telomerase activity and interfere with the telomere functions in cancer cells. Theseresults provide new insights into understanding the biomedical effects of sWnTs and thebiological importance of i-motif DnA.