Photodynamic Therapy with Metal Complexes

Photodynamic therapy harnesses light-activated photosensitisers to generate cytotoxic reactive oxygen species precisely within diseased tissue. Metal complexes confer distinct advantages over organic dyes, including tunable absorption across visible and near-infrared wavelengths, long-lived excited states and high photostability. By modulation of the metal centre, oxidation state and ligand architecture, it is possible to favour Type II photochemistry for singlet oxygen production or Type I pathways yielding radical species, thus addressing challenges of tumour hypoxia. Recent strategies incorporate oxygen-releasing peroxo complexes, hypoxia-tolerant Type I sensitisation and self-assembling nanostructures to enhance in vivo persistence and selectivity. Conjugation to targeting peptides or antibodies further refines tumour accumulation, while intrinsic luminescence enables concurrent imaging and therapy. Bridging fundamental photophysics with scalable synthesis under Good Manufacturing Practice is key to global clinical translation. Metal-based photosensitisers now show promise not only in oncology but also in antimicrobial and vascular applications, heralding a new era of precision photomedicine.

Research from Nature Portfolio

Innovative polymerisation of cyclometalated iridium units into metallopolymers has yielded Type I photosensitisers with enhanced absorption in the red to near-infrared region, achieving a marked increase in reactive oxygen species generation and targeted tumour uptake via integrin-binding motifs. In parallel, the exploitation of metallophilic palladium interactions has enabled in vivo self-assembly of supramolecular nanostructures that persist in circulation and accumulate selectively in melanoma models, delivering a potent Type I photodynamic effect upon green light activation. Additionally, the design of an osmium-peroxo pro-complex has demonstrated oxygen-independent activation in hypoxic tumour microenvironments, releasing superoxide anions on irradiation and concurrently inducing chemotherapeutic activity, thereby overcoming limitations posed by low oxygen levels.

Photodynamic Therapy with Metal Complexes publication trend

The graph below shows the total number of articles in photodynamic therapy with metal complexes across all publications each year (not limited to Nature Index journals).

Technical terms

Photosensitiser: A molecule that absorbs light and transfers energy to oxygen or substrates to generate cytotoxic species.

Type I photochemistry: A pathway involving electron or hydrogen transfer to form radical species capable of oxidising biomolecules.

Type II photochemistry: A mechanism in which energy transfer from the excited photosensitiser produces singlet oxygen.

Hypoxia: A condition of reduced oxygen availability common in solid tumours, which impairs oxygen-dependent therapies.

Reactive oxygen species (ROS): Highly reactive molecules, including superoxide and singlet oxygen, that can damage cellular components.

References

1. Metallopolymer strategy to explore hypoxic active narrow-bandgap photosensitizers for effective cancer photodynamic therapy. Nature Communications (2024).
2. In vivo metallophilic self-assembly of a light-activated anticancer drug. Nature Chemistry (2023).
3. An osmium-peroxo complex for photoactive therapy of hypoxic tumors. Nature Communications (2022).
4. New Designs for Phototherapeutic Transition Metal Complexes. Angewandte Chemie International Edition (2019).
5. Enhancing the ROS generation ability of a rhodamine-decorated iridium( iii ) complex by ligand regulation for endoplasmic reticulum-targeted photodynamic therapy. Chemical Science (2020).