title: In-cell optical imaging of exogenous G-quadruplex DNA by fluorogenic ligands.
abstract: 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.
authors.affiliation: Institute of Biophotonics, National Yang-Ming University, Taipei 11221, Taiwan, Republic of China, Institute of Atomic and Molecular Sciences, Academia Sinica, Taipei 106, Taiwan, Republic of China and Department of Chemistry, National Taiwan University, Taipei 106, Taiwan, Republic of China.
authors.forename: Ting-Yuan
authors.initials: TY
authors.lastname: Tseng
authors.forename: Zi-Fu
authors.initials: ZF
authors.lastname: Wang
authors.forename: Cheng-Hao
authors.initials: CH
authors.lastname: Chien
authors.forename: Ta-Chau
authors.initials: TC
authors.lastname: Chang
mesh_terms: D002227:Carbazoles / Q000737:chemistry; D045744:Cell Line, Tumor; D004247:DNA / Q000737:chemistry; D031541:Fluorescence Resonance Energy Transfer; D005456:Fluorescent Dyes; D054856:G-Quadruplexes; D006147:Guanine / Q000737:chemistry; D006801:Humans; D008024:Ligands; D018613:Microscopy, Confocal; D009838:Oligodeoxyribonucleotides / Q000737:chemistry*; D061848:Optical Imaging; D011726:Pyridinium Compounds / Q000737:chemistry
chemical_list: C486012:3,6-bis(1-methyl-4-vinylpyridium)carbazole diiodide; D002227:Carbazoles; D005456:Fluorescent Dyes; D008024:Ligands; D009838:Oligodeoxyribonucleotides; D011726:Pyridinium Compounds; D006147:Guanine; D004247:DNA
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