Luminescent ruthenium on gold nanoparticles; novel DNA probes for cancer theranostics

Madeira Girio, Patrícia Alexandra (2024). Luminescent ruthenium on gold nanoparticles; novel DNA probes for cancer theranostics. University of Birmingham. Ph.D.

Preview

Girio2024PhD.pdf
Text - Accepted Version
Available under License All rights reserved.
Download (8MB) | Preview

Abstract

Ruthenium (II) polypyridyl complexes have been extensively investigated for cancer research as imaging probes or as therapeutic drug due to their photothermal stability, large stoke shifts, relatively long lifetimes, and potential anticancer activity. To overcome issues of solubility and delivery, gold nanoparticles (AuNPs) have emerged as nano carriers due to their relative chemical inertness, large surface area with possibilities of functionalisation as well as their unique multimodal imaging properties due to their surface plasmon resonance and electron density. Three ruthenium (II) complexes carrying DNA intercalating groups (RuPhenL1, RuPhenL2 and RuDppzL2) were successfully attached onto the surface of 13 nm and 25 nm gold nanoparticles. Luminescence studies of Au.RuPhenL1 and Au.RuPhenL2 revealed enhancement of the ruthenium luminescence lifetime upon attachment to gold nanoparticles by considering the type of ancillary ligands around the metal in combination with the type of surfactant used to stabilise the AuNPs. Furthermore, the negatively charged Au.RuPhenL2 and Au.RuDppzL2 conjugates demonstrated to have a high binding affinity with DNA, with binding constants comparable to known intercalators (Ka= 106 M-1). Unsurprisingly, Au.RuDppzL2 had the strongest interaction with DNA. For the first time, the interaction of the Au.RuPhenL2 and Au.RuDppzL2 conjugates is visualised by Transmission Electron Microscopy (TEM) and Energy Dispersed X-ray Spectroscopy (EDX). Intercalation and electrostatic interactions with an uncoiling of DNA, are the suggested modes of binding between AuNP.Ru conjugates and DNA. The luminescent nanoparticles (Au.RuPhenL1, Au.RuPhenL2 and Au.RuDppzL2) accumulated in the cytoplasm and in the nucleus of A549 cells just after 4 hours incubation. The larger 25 nm AuNPs showed higher cellular uptake than the 13 nm ones for Au.RuPhenL1 and Au.RuPhenL2. However, in the case of Au.RuDppzL2 there was high uptake for both 13 nm and 25 nm sized nanoparticles. All the AuNP.Ru conjugates showed phototoxicity in the nanomolar range for A549 cells upon visible light irradiation at 535 nm, whereas no toxicity was found in the dark. Overall, novel AuNP.Ru conjugates demonstrated promising results as DNA probes for imaging and as pro-drugs for photodynamic therapy for an effective theranostics strategy against cancer.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):