Photosensitizers Based on G-Quadruplex Ligand for Cancer Photodynamic Therapy

Abstract

G-quadruplex (G4) is the non-canonical secondary structure of DNA and RNA formed by guanine-rich sequences. G4-forming sequences are abundantly located in telomeric regions and in the promoter and untranslated regions (UTR) of cancer-related genes, such as RAS and MYC. Extensive research has suggested that G4 is a potential molecular target for cancer therapy. Here, we reviewed G4 ligands as photosensitizers for cancer photodynamic therapy (PDT), which is a minimally invasive therapeutic approach. The photosensitizers, such as porphyrins, were found to be highly toxic against cancer cells via the generation of reactive oxidative species (ROS) upon photo-irradiation. Several porphyrin derivatives and analogs, such as phthalocyanines, which can generate ROS upon photo-irradiation, have been reported to act as G4 ligands. Therefore, they have been implicated as promising photosensitizers that can selectively break down cancer-related DNA and RNA forming G4. In this review, we majorly focused on the potential application of G4 ligands as photosensitizers, which would provide a novel strategy for PDT, especially molecularly targeted PDT (mtPDT).

Evaluating the Influence of a G-Quadruplex Prone Sequence on the Transactivation Potential by Wild-Type and/or Mutant P53 Family Proteins through a Yeast-Based Functional Assay

“…Indeed, contemporary research has demonstrated the importance of G4s in various cellular processes, including interactions with TFs [ 60 , 61 , 62 , 63 ]. Moreover, the targeting of the unique structure of G4s is proposed as a good tool for various diseases therapies including cancer [ 64 , 65 , 66 , 67 , 68 ].…”

Evolution of Diverse Strategies for Promoter Regulation

“…Several studies demonstrate that G-quadruplex prone sequences are abundant in human promoters [46,58]. Notably, the distinct abundance of G-prone sequences was detected in the promoters of oncogenes, suggesting the potential to use G-quadruplex regulation in cancer treatment [47,59]. Probably the best explored G-quadruplex in promoters is a sequence from the human c-Myc oncogene [60,61].…”

Cation and light-responsive frameworks from non-canonical amphiphilic DNA nanostructures

“…Besides K + chelation, the material can also be be disassembled upon addition of a G4-binding porphyrin photosensitiser and exposure to longwave UV light (395-400 nm), the combination of which, as previously described, disrupts the quadruplex through guanine photo-oxidation. [35][36][37][38][39] This additional mechanism is irreversible but enables precise spatial control over the response. Owing to the combined assembly reversibility, multistimuli-responsiveness, and cargo-loading capabilities, we believe that Quad-Stars hold significant potential for applications such as smart biosensors and drug delivery carriers.…”