Abstract
Photodynamic therapy (PDT) is a remarkable alternative or complementary technique to chemotherapy, radiotherapy or immunotherapy to treat certain forms of cancer. The synergistic effect of light, photosensitizer (PS) and oxygen allows for the treatment of tumours with an extremely high spatio-tumoral control, therefore minimizing the severe side effects usually observed in chemotherapy. The currently employed PDT PSs based on porphyrins have, in some cases, some limitations, which include a low absorbance in the therapeutic window, a low body clearance, photobleaching, among others. In this context, Ru(ii) polypyridyl complexes are interesting alternatives. They have low lying excited energy states and the presence of a heavy metal increases the possibility of spin-orbit coupling. Moreover, their photophysical properties are relatively easy to tune and they have very low photobleaching rates. All of these make them attractive candidates for further development as therapeutically suitable PDT PSs. In this review, after having presented this field of research, we discuss the developments made by our group in this field of research since 2017. We notably describe how we tuned the photophysical properties of our complexes from the visible region to the therapeutically suitable red region. This was accompanied by the preparation of PSs with enhanced phototoxicity and high phototoxicity index. We also discuss the use of two-photon excitation to eradicate tumours in nude mice. Furthermore, we describe our approach for the selective delivery of our complexes using targeting agents. Lastly, we report on our very recent synergistic approach to treat cancer using bimetallic Ru(ii)-Pt(iv) prodrug candidates.
Highlights
The use of light holds enormous potential in anticancer chemotherapy since it offers the possibility of controlling, at a desired time and place, the release of cytotoxic species from an inert prodrug
In another pathway, excited electrons can go from the 1ES to the 3ES through intersystem crossing (ISC) and returns to the 1GS by radiative or nonradiative decay
In one of our previous works, we found that a 7-methoxy substituted dppz-containing RPC, namely [Ru(bpy)2(dppz-7OMe)]2+, had a good phototoxic index (PI = IC50 in the dark/ IC50 upon light irradiation) of 42 against human cervical cancer cells (HeLa) cells upon irradiation with 420 nm light.[19]
Summary
The use of light holds enormous potential in anticancer chemotherapy since it offers the possibility of controlling, at a desired time and place, the release of cytotoxic species from an inert prodrug. This value slightly decreased (PI = 1.4) in the presence of 480 nm light From these observations, we concluded that the increase in conjugation and dimethylamine or methoxy functionalization in the bpy or bpy type ligands may have a positive role for red-shifted absorption maxima and phototoxicity. Undesired phototoxic effects on a healthy cell can be observed, the physician is only applying light at a selected area.[1,31] To overcome this limitation, there is a need for the development of a suitable drug delivery system to increase the amount of PS delivered to the tumour In this context, there is a strong interest of our group towards the design and development of complexes conjugated to small molecules, peptides, antibodies or proteins, etc. We conclude that the transcobalamin pathway was not involved in the uptake of our complex
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