Photodynamic Therapy Using Ruthenium Complexes

Photodynamic therapy (PDT) harnesses light-activated compounds to generate cytotoxic species that destroy malignant tissues with spatial and temporal precision. Ruthenium complexes offer a versatile platform for PDT owing to their strong visible-to-near-infrared absorption, high photostability and tunable excited-state lifetimes. Upon irradiation, these complexes undergo efficient intersystem crossing to long-lived triplet states, enabling energy transfer to molecular oxygen and the production of singlet oxygen or other reactive oxygen species. Ligand design further allows red-shifting of absorption bands, two-photon excitation and targeted delivery through bioconjugation or nanoparticle encapsulation. The unique photochemistry of ruthenium centres, combined with modular ligand frameworks, facilitates both direct oxidative damage of biomolecules and photoactivated release of cytotoxic agents. Collectively, these attributes have driven advances towards deeper tissue penetration, hypoxia tolerance and reduced off-target effects, positioning ruthenium-based photosensitisers as promising candidates for next-generation cancer therapies.

Research from Nature Portfolio

Recent studies have demonstrated the power of in silico design to optimise ruthenium(II) polypyridyl complexes for both one- and two-photon PDT. By incorporating extended π-conjugated ligands, researchers have achieved absorption cross-sections in the biological optical window that exceed those of earlier agents by an order of magnitude. These compounds remain inert in the dark but induce potent phototoxicity in two-dimensional cell monolayers, three-dimensional tumour spheroids and in vivo models, including the eradication of resistant tumours under clinically relevant irradiation conditions. Complementary work has expanded the toolkit of two-photon-absorbing ruthenium complexes capable of near-infrared activation. Although primarily explored in catalytic contexts, these designs underscore strategies for deep-tissue excitation and efficient triplet-state formation, paving the way for translatable photosensitisers that combine precise spatial control with minimal photobleaching.

Photodynamic Therapy Using Ruthenium Complexes publication trend

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

Technical terms

Photosensitiser: A compound that absorbs light and transfers energy to molecular oxygen or other substrates, generating cytotoxic species.

Singlet oxygen: A highly reactive form of oxygen (¹O₂) produced by energy transfer from an excited photosensitiser, responsible for oxidative damage in PDT.

Two-photon absorption: The simultaneous uptake of two low-energy photons to reach an excited state, enabling deeper tissue penetration with near-infrared light.

Phototoxicity: The induction of cell death or damage upon light activation of a photosensitiser, distinct from dark toxicity.

Hypoxia: A condition of low oxygen concentration in tissues, which can limit traditional PDT but may be addressed by oxygen-independent mechanisms.

References

1. Rationally designed ruthenium complexes for 1- and 2-photon photodynamic therapy. Nature Communications (2020).
2. Two-photon-absorbing ruthenium complexes enable near infrared light-driven photocatalysis. Nature Communications (2022).
3. Ruthenium (II) polypyridyl complexes as two-photon absorbers and sensitizers: Design, structure-properties relationships and applications. Coordination Chemistry Reviews (2024).
4. Polyphosphoester-stabilized cubosomes encapsulating a Ru(II) complex for the photodynamic treatment of lung adenocarcinoma. Journal of Colloid and Interface Science (2024).
5. A Dinuclear Ruthenium(II) Complex Excited by Near-Infrared Light through Two-Photon Absorption Induces Phototoxicity Deep within Hypoxic Regions of Melanoma Cancer Spheroids. Journal of the American Chemical Society (2020).