Hybrids Based on Graphene Oxide and Porphyrin as Tools for Detection and Stabilization of DNA G-Quadruplexes

Abstract

Telomerase inhibition has been an important strategy in cancer therapies, but for which effective drugs are still required. Here, noncovalent hybrid nanoplatforms containing the tetracationic 5,10,15,20-tetrakis(1-methyl-pyridinium-4-yl)porphyrin (TMPyP) and graphene oxide (GO) were prepared for promoting telomerase inhibition through the selective detection and stabilization of DNA guanine-quadruplex (G-Q) structures. Upon binding TMPyP to the GO sheets, the typical absorption bands of porphyrin have been red-shifted and the fluorescence emission was quenched. Raman mapping was used for the first time to provide new insights into the role of the electrostatic and π-π stacking interactions in the formation of such hybrids. The selective recovery of fluorescence observed during the titration of TMPyP@GO with G-Q, resembles a selective "turn-off-on" fluorescence sensor for the detection of G-Q, paving the way for a new class of antitumor drugs.

Figure 1

UV–vis absorption spectra (350–550 nm) for the titration of TMPyP (1 mL, 2 μM) with GO (1 mg/mL), in aqueous solution. The inset corresponds to the fluorescence emission spectra (550–750 nm), at 423 nm excitation.

Figure 2

Spectrofluorimetric titrations (550–750 nm, excitation at 423 nm) of TMPyP (1 mL, 2 μM) with DNA oligonucleotides: (A) 4GC (able to form duplex structures), (B) G-Q (T₂AG₃)₄.

Figure 3

Spectrofluorimetric titrations (550–750 nm, excitation at 423 nm) of a typical TMPyP@GO solution (1 mL, 2 μM) with DNA oligonucleotides: (A) 4GC; (B) G-Q (T₂AG₃)₄.

Figure 4

(A) Optical microscope image of the TMPyP@GO hybrid. (B) The Raman spectra of the TMPyP@GO hybrid acquired at different sample regions (1–3) indicated in (A); pure TMPyP and GO sheets.

Figure 5

Raman images of TMPyP@GO hybrids, in which the vertical bar shows the color profile with the relative intensity scale. The images were obtained by using the integrated intensity of the Raman bands of TMPyP at 978 cm^–1 (A) and at 1006 cm^–1 (B), and the Raman band of GO at 1350 cm^–1 (C). The combined Raman image (D) was obtained by using two different Raman spectra for the TMPyP decorating GO sheets, as shown in (E).