Photoactivated chemotherapy (PACT): the potential of excited-state d-block metals in medicine

Abstract

The fields of phototherapy and of inorganic chemotherapy both have long histories. Inorganic photoactivated chemotherapy (PACT) offers both temporal and spatial control over drug activation and has remarkable potential for the treatment of cancer. Following photoexcitation, a number of different decay pathways (both photophysical and photochemical) are available to a metal complex. These pathways can result in radiative energy release, loss of ligands or transfer of energy to another species, such as triplet oxygen. We discuss the features which need to be considered when developing a metal-based anticancer drug, and the common mechanisms by which the current complexes are believed to operate. We then provide a comprehensive overview of PACT developments for complexes of the different d-block metals for the treatment of cancer, detailing the more established areas concerning Ti, V, Cr, Mn, Re, Fe, Ru, Os, Co, Rh, Pt, and Cu and also highlighting areas where there is potential for greater exploration. Nanoparticles (Ag, Au) and quantum dots (Cd) are also discussed for their photothermal destructive potential. We also discuss the potential held in particular by mixed-metal systems and Ru complexes.

Photo-Induced Pyridine Substitution in cis-[Ru(bpy)2(py)2]Cl2: A Snapshot by Time-Resolved X-ray Solution Scattering

“…4,[13][14][15][16][17][18] Obtaining structural information on transient species generated by light excitation is therefore crucial to the field of photoactivatable metal-based anticancer agents. It can reveal the mechanism of activation of the 'prodrug' helping to understand the overall mechanism of action of the metal complex in cells.…”

Photoactivatable Organometallic Pyridyl Ruthenium(II) Arene Complexes

“…1 Such a strategy has been applied to (poly)pyridyl complexes as diagnostic and therapeutic agents. 2,3, 4 The basic rationale involves the modification of the Ru II molecules by introducing a group that can be selectively cleaved by the absorption of light, promoting its release and offering the possibility of controlling the location, timing, and dosage of the therapeutic metal complex.…”

“…Studies of CT-DNA interactions in cell-free media suggest combined weak monofunctional coordinative and intercalative binding modes. The Ru II arene complexes [(η 6 -p-cym)Ru(bpm)(Py)] 2+ (1), [(η 6 -p-cym)Ru(bpm)(4-MeOPy)] 2+ (3), [(η 6 -p-cym)Ru(4,4'-biPy)] 2+ (4), [(η 6 -hmb)Ru(bpm)(Py)] 2+ (8), [(η 6 -ind)Ru(bpm)(Py)] 2+ (9), [(η 6 -p-cym)Ru(phen)(Py)] 2+ (10),…”

Lightening up Ruthenium Complexes to Fight Cancer?

“…[15] Researchers have investigated a great variety of compounds with light-induced activity, but whose mechanism of toxicity does not rely on oxygen, to apply them as PACT agents. [6,57,58] Among the different (metalbased) compounds exploited in this field of research, Ru complexes have played an important role, as recently reviewed by our group. [19] We also actively contributed to the field by designing, to the best of our knowledge, the first substitutionally inert Ru PACT prodrug, whose activity can be turned on via light exposure.…”