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.

Functionalization of Graphene Oxide with Porphyrins: Synthetic Routes and Biological Applications

“…These alterations may be ascribed to the molecular flattening of the porphyrin molecules onto GO sheets, an effect that causes an increase in the energy of the ground state of the porphyrins. [46,152,153] Fluorescence spectroscopy…”

“…Fluorescence time-profiles show that the fluorescence lifetime of photoexcited porphyrins in GO/porphyrin hybrids is shorter than the lifetime of free porphyrins, thus suggesting a charge-separation and/or energy transfer in the hybrid via 1 H 2 P*. [46,76,152,153,175] Raman spectroscopy…”

“…Diagnosis vibrational bands of the porphyrins can indicate the successful interaction of both components and relevant interactions can be investigated. [153,160,176] FTIR spectroscopy…”

Multimodal use of the porphyrin TMPyP: From cancer therapy to antimicrobial applications

“…The use of TMPyP for the detection and quantification of nucleic-acid-based molecules, such as G-quadruplexes, have been reported, taking advantage of the high affinity of this porphyrin towards DNA and its fluorescent properties. In a recent publication, Monteiro et al used a graphene oxide nanoplatform to non-covalently bind TMPyP [88]. The fluorescence of the porphyrin was quenched in the hybrid platforms but, upon the addition of oligonucleotide sequences corresponding to G-quadruplexes, TMPyP was tritiated and detached from the graphene oxide, allowing the recovery of its characteristic red fluorescence.…”

“…G-quadruplexes are secondary structures of the DNA formed as a result of the interaction of nucleotides in guanine-rich sequences [88]. They have been described as potent molecular targets for cancer therapy since their stabilization can lead to cell growth and cell division inhibition [89].…”