Transition metal complexes as photosensitisers in one- and two-photon photodynamic therapy

Abstract

Photodynamic therapy (PDT) exploits light-activated compounds for therapeutic use. It relies on a photosensitiser (PS) that is inactive in the absence of light. When irradiated, the PS absorbs light and is promoted to a higher energy, "excited" state (PS*), which is either toxic to cells in itself, or triggers formation of other species which are toxic to cells, and hence particular wavelengths of light can be used to induce light-dependent cell killing. In PDT occurring via the so-called type I and type II mechanisms, the PS* engages in energy transfer to dioxygen present in cells and tissues. This process generates highly reactive singlet oxygen (1 O2) and/or other reactive oxygen species (ROS) which in turn cause damage in the immediate vicinity of irradiation, and ultimately can lead to cell death. Whilst the main focus of research for the last 50 years has been on organic molecules or porphyrins as sensitisers, there is now emerging interest in extending the use of transition metal (TM) complexes can display intense absorption in the visible region, and many also possess high two-photon absorption crosssections, which enable two-photon excitation with NIR light. As with any other type of photosensitiser, the issues to consider whilst designing a TM complex as a photosensitiser include cell permeability, efficient absorption of NIR light for deeper penetration, preferential affinity to cancer cells over healthy cells, targeted intracellular localisation, and lack of side effects. This review summarises recent developments involving photosensitisers containing, Ru(II), Os(II), Pt, Ir(III), and Re(I), and the approaches used to address the above requirements. Several remarkable recent advances made in this area, including the first clinical trial of a metal complex as a photosensitiser, indicate the bright future of this class of compounds in PDT.

A self-assembled Ru–Pt metallacage as a lysosome-targeting photosensitizer for 2-photon photodynamic therapy

“…Synthesis of the SCCs. Ru(bpy) 3 2+ (bpy = 2,2′-bipyridine) and its derivatives have widespread applications not only in PDT (7,56,(58)(59)(60) but also in photoredox catalysis (61) and photovoltaics (62). A ditopic, Ru(II)-containing donor 1 was obtained by replacing 1 bpy group of Ru(bpy) 3…”

A Ru(II) polypyridyl complex bearing aldehyde functions as a versatile synthetic precursor for long-wavelength absorbing photodynamic therapy photosensitizers

“…To overcome these limitations, there is a need for modification of existing PSs or the development of new classes of PSs. [1][2][3][4][5][6][7][8][9][10][11] Among other classes of compounds, the development of Ru(II) polypyridyl complexes is receiving increasing attention due to their excellent properties (i.e. high water solubility, high chemical stability and photostability, intense luminescence, large Stokes shifts, high 1 O2 production).…”

“…Therefore, a lot of efforts have recently been made towards the development of Ru(II)-based PDT PSs showing a red shift in absorbance with respect to parent compounds. [9][10][11][12][13][14] As a highly investigated class of compounds, [Ru(phen)3] 2+ derivatives have been studied as PDT PSs. [15][16][17][18] Several examples have shown that the photophysical properties, including absorption, emission as well as excited states lifetimes can be influenced by choice of the coordinated ligands.…”

Evaluation of the Potential of Cobalamin Derivatives Bearing Ru(II) Polypyridyl Complexes as Photosensitizers for Photodynamic Therapy

“…Although the use of such compounds as PDT PS against cancer is relatively recent, the results are spectacular with one of such compounds, TLD-1433, having recently completed phase I clinical trial against bladder cancer. [2,[6][7][8][9][10] We note that to reach the therapeutic window for PDT treatment (ca. 600 to 800 nm), some Ru(II) polypyridyl complexes were found to be good PSs for two-photon PDT, [11 -13] further illustrating the versatility of ruthenium in medicinal chemistry.…”