abstract
The functionalization of deoxyribonucleic acid (DNA) with nanomaterials is a promising strategy to optimize the loading and efficiency of drugs in targeted clinical therapies. Herein we report a novel approach to construct arrays comprising blue- (B) or aqua green- (AG) emitting ethylenediamine-modified graphene quantum dots (GQDs) and DNA oligonucleotides that are able to fold into different structures, namely G-quadruplexes (G4s). The obtained results indicate that GQDs partially modulate the conformation of oligonucleotides, resulting in GQDs-DNA bioconjugates with higher affinity to carry 5,10,15,20-tetrakis(1-methylpyridinium-4-yl)porphyrin (TMPyP), in comparison to non-modified DNA sequences. TMPyP shows a higher affinity, expressed by a lower dissociation constant (K-D), to GQDs-B-G4-1 (0.229 & mu;M) and to GQDs-AG-G4-1 (K-D of 0.326 & mu;M) in comparison with non-modified G4-1 (K-D of 0.440 & mu;M). The carrier systems with the highest affinity to TMPyP correspond to GQDs-AG with telomeric unimolecular G4 sequence (GQDs-AG-G4-2, K-D of 0.111 & mu;M) and GQDs-AG with a non-G4 sequence (GQDs-AG-non-G4, K-D of 0.110 & mu;M), followed by their analogues with GQDs-B. While uncovering terra incognita, it is anticipated that GQDs-DNA arrays may be potential photoluminescent nanovehicles to carry other cationic anticancer drugs and allow more targeted therapies.
subject category
Chemistry
authors
Monteiro, AR; Ramos, CIV; Fateixa, S; Neves, MGPMS; Trindade, T
our authors
Sara Fateixa
Junior Researcher
Tito Trindade
Full professorProjects
CICECO - Aveiro Institute of Materials (UIDB/50011/2020)
CICECO - Aveiro Institute of Materials (UIDP/50011/2020)
Associated Laboratory CICECO-Aveiro Institute of Materials (LA/P/0006/2020)
acknowledgements
this work was supported by LAQV-REQUIMTE (UIDB/50006/2020 and UIDP/50006/2020) and CICECO-Aveiro Institute of Materials (UIDB/50011/2020, UIDP/50011/2020 & LA/P/0006/2020), funded by FCT/MEC (PIDDAC) and where applicable co-financed by the FEDER-Operational Thematic Program for Competitiveness and Internationalization-COMPETE 2020, within the PT2020 Partnership Agreement. Ana R. Monteiro thanks the FCT and ESF (European Social Fund) for her PhD grant ref. SFRH/BD/137356/2018. Similarly, Sara Fateixa and Catarina I. V. Ramos acknowledge the costs of their research contracts (REF.-069-88-ARH/2018 and REF.-047-88-ARH/2018, respectively) resulting from the FCT hiring funded by National funds (OE), through FCT, I.P., in the scope of the framework contract foreseen in the numbers 4, 5, and 6 of the article nr. 23, of the Decree-Law 57/2016, of August 29, changed by the law 57/2017, of July 19. Graphical content was partially designed with BioRender.