As the leading nanodevice candidate, single-walled carbon nanotubes (SWNTs) have potential therapeutic applications in gene therapy and novel drug delivery. We found that SWNTs can inhibit DNA duplex association and selectively induce human telomeric i-motif DNA formation by binding to the 5-end major groove under physiological conditions or even at pH 8.0. SWNT binding to telomeric DNA was studied by UV melting, NMR, S1 nuclease cleavage, CD, and competitive FRET methods. These results suggest that SWNTs might have the intriguing potential to modulate human telomeric DNA structures in vivo, like biologically relevant B-A and B-Z DNA transitions, which is of great interest for drug design and cancer therapy. Since the discovery of the DNA i-motif, the formation and biological function of this unique structure have attracted much attention, and significant progress in characterizing the i-motif has been made in recent years (1, 2). The biological importance of the intramolecular i-motif is evidenced by its involvement in human telomeric and centromeric DNA structures and RNA intercalated structures, and by the discovery of several proteins that bind specifically to C-rich telomeric DNA fragments capable of forming i-motifs (2). Along with human telomeric G-quadruplex DNA, the i-motif has been an attractive drug target for cancer chemotherapy and for modulation of gene transcription (2-9). Human telomeres consist of tandem repeats of the double-stranded DNA sequence (5Ј-TTAGGG):(5Ј-CCCTAA) (3-9). The G-rich strand can form a four-stranded G-quadruplex consisting of G-quartets, whereas its complementary C-rich strand may adopt i-motif structures with intercalated C⅐C ϩ base pairs ( Fig. 1). Significantly, G-quadruplex formation was shown to inhibit the activity of telomerase, an enzyme that stabilizes chromosome ends by adding tandem telomeric DNA repeats to the 3Ј single-stranded overhangs (4,5,10). In contrast to the majority of normal human somatic cells, most tumor cells express telomerase, and telomerase expression is essential for their indefinite proliferative capacities. Therefore, the therapeutic targeting of telomerase activity has been considered a promising approach to cancer therapy (4, 5, 10). Several small molecules have been shown to efficiently inhibit telomerase activity through the stabilization of G-quadruplex DNA (4, 5). Only two molecules that can stabilize both G-quadruplex and i-motif DNA have been identified (11,12). To our knowledge, a ligand that can selectively stabilize i-motif DNA but not G-quadruplex DNA has not been reported.As the leading nanodevice candidate, single-walled carbon nanotubes (SWNTs) have potential applications ranging from gene therapy to novel drug delivery to membrane separation (13-17). B-Z DNA transition has been achieved on the surfaces of SWNTs (18). Recently we reported that SWNTs bind to the DNA major groove and can induce a sequence-dependent B-A DNA transition (19). In the present study we show that SWNTs can selectively stabilize human telomeric i-motif DN...

Single-walled carbon nanotubes (SWNTs) have been considered as the leading candidate for nanodevice applications ranging from gene therapy and novel drug delivery to membrane separations. The miniaturization of DNA-nanotube devices for biological applications requires fully understanding DNA-nanotube interaction mechanism. We report here, for the first time, that DNA destabilization and conformational transition induced by SWNTs are sequence-dependent. Contrasting changes for SWNTs binding to poly[dGdC]:poly[dGdC] and poly[dAdT]:poly[dAdT] were observed. For GC homopolymer, DNA melting temperature was decreased 40°C by SWNTs but no change for AT-DNA. SWNTs can induce B–A transition for GC-DNA but AT-DNA resisted the transition. Our circular dichroism, competitive binding assay and triplex destabilization studies provide direct evidence that SWNTs induce DNA B–A transition in solution and they bind to the DNA major groove with GC preference.

The increasing worldwide demand for carbon nanotubes (CNTs) and increasing concern regarding how to safely develop and use CNTs are requiring a low-cost, simple, and highly sensitive CNT detection assay for toxicological evaluation and environmental monitoring. However, this goal is still far from being achieved. All the current CNT detection techniques are not applicable for automation and field analysis because they are dependent on highly expensive special instruments and complicated sample preparation. On the basis of the capability of single-walled carbon nanotubes (SWNTs) to specifically induce human telomeric i-motif formation, we design an electrochemical DNA (E-DNA) sensor that can distinguish single- and multiwalled carbon nanotubes both in buffer and in cell extracts. The E-DNA sensor can selectively detect SWNTs with a direct detection limit of 0.2 ppm and has been demonstrated in cancer cell extracts. To the best of our knowledge, this is the first demonstration of a biosensing technique that can distinguish different types of nanotubes. Our work will provide new insights into how to design a biosensor for detection of carbon nanotubes.