Guanine-rich oligonucleotides (GROs) are promising therapeutic candidate for 
cancer treatment and other biomedical application. We have introduced a 
G-quadruplex (G4) ligand, 3,6-bis(1-methyl-4-vinylpyridinium) carbazole 
diiodide, to monitor the cellular uptake of naked GROs and map their 
intracellular localizations in living cells by using confocal microscopy. The 
GROs that form parallel G4 structures, such as PU22, T40214 and AS1411, are 
detected mainly in the lysosome of CL1-0 lung cancer cells after incubation for 
2 h. On the contrary, the GROs that form non-parallel G4 structures, such as 
human telomeres (HT23) and thrombin binding aptamer (TBA), are rarely detected 
in the lysosome, but found mainly in the mitochondria. Moreover, the 
fluorescence resonant energy transfer studies of fluorophore-labeled GROs show 
that the parallel G4 structures can be retained in CL1-0 cells, whereas the 
non-parallel G4 structures are likely distorted in CL1-0 cells after cellular 
uptake. Of interest is that the distorted G4 structure of HT23 from the 
non-parallel G4 structure can reform to a probable parallel G4 structure induced 
by a G4 ligand in CL1-0 living cells. These findings are valuable to the design 
and rationale behind the possible targeted drug delivery to specific cellular 
organelles using GROs.