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. 2009 Dec 28:(48):10690-701.
doi: 10.1039/b917753a. Epub 2009 Nov 11.

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

Nicola J Farrer  1 , Luca Salassa, Peter J Sadler
Affiliations

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

Nicola J Farrer et al. Dalton Trans. .

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.

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Figures

Figure 1
Figure 1
Table of d-block metals, coloured to demonstrate the PACT potential of each metal, based on recent literature. Bold = well-documented photochemical activity. Underlined = well-documented anticancer activity. Bold + underlined = photochemical + anticancer activity.
Figure 2
Figure 2
Simplified orbital and excited-state diagram for a d6 metal complex with octahedral coordination (strong crystal field is assumed). Each black arrow (↑↓) represents an electron with its associated spin. Coloured arrows (formula image) represent the electron involved in each electronic transition. In the singlet state electrons are spin down (formula image), while in the triplet state they are spin up (formula image).
Figure 3
Figure 3
Jabłonski energy diagram. All possible physical processes triggered by light excitation of a d6 metal complex are represented by dotted (– – – radiationless) and solid (——, radiative) lines.
Figure 4
Figure 4
(a) OCTBP, a methylated [cis-Rh(phen)2(Cl)2]Cl derivative which shows phototoxicity towards tumour cells (λirr> 500 nm). (b) dinuclear Rh complex which shows 34 × increase in cytotoxicity when irradiated (λirr = 400–700 nm) (c) Pd-based PDT agent TOOKAD currently in clinical trials (structure adapted from reference 71).
Figure 5
Figure 5
(a) Calculated (TDDFT) and experimental absorption spectrum of cis,trans,cis-[Pt(N3)2(OH)2(NH3)2] in H2O. The excited states are shown as vertical bars with heights equal to their extinction coefficients. Transitions S1–S4 have all dissociative character since they involve (b) the σ-antibonding orbitals LUMO and LUMO+1.
Figure 6
Figure 6
Mixed metal Ru-Rh-Ru complex of Brewer et al.
Figure 7
Figure 7
Photoadduct formation during the photoirradiation of [Ru(TAP)3]2+ in the presence of GMP. The photoproduct is obtained after several steps of purification and acidification.
Figure 8
Figure 8
Schematic representation of the behaviour of Ru-ODN(G) (a)in the absence of complementary strands, (b) in the presence of non-complementary strands, and (c) in the presence of complementary target strands (adapted from reference [105]).
See this image and copyright information in PMC

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