Efficient Singlet Oxygen Generation in Metal Nanoclusters for Two-Photon Photodynamic Therapy Applications

The generation of singlet oxygen (¹O₂) has been established as the principal mechanism of photodynamic therapy (PDT). Various dyes, metal nanoparticles, and clusters have been shown to sensitize ¹O₂. However, metal nanoclusters are even more promising candidates as photosensitizers for this purpose. By understanding the optical properties that lead to efficient ¹O₂ generation, one can fully realize their potential as PDT photosensitizers. Three different metal nanoclusters, Au₂₅, Ag₃₂, and Au₁₄₄, are investigated for their ¹O₂ generation efficiency. The Au₁₄₄ showed a ¹O₂ generation rate that is 2 orders of magnitude higher than that for Au₂₅ and Ag₃₂, and several orders of magnitude higher than nanoparticles (>5 nm) due to Au₁₄₄'s high absorption cross section-to-volume ratio. The effectiveness of PDT in live cells with nanoclusters was demonstrated by two-photon excitation compared to one-photon excitation. The implication of these results points toward new efficient two-photon ¹O₂ sensitizers for photodynamic therapy.