Leveraging Spectral Matching between Photosensitizers and Upconversion Nanoparticles for 808 nm-Activated Photodynamic Therapy

Upconversion nanoparticles (UCNPs) are promising platforms to enhance the therapeutic response of cancer cells toward photodynamic therapy (PDT). When coupled with UCNPs, the photosensitizers in PDT are indirectly activated by near-infrared (NIR) excitation that allows for deeper tissue penetration and reduced attenuation. To achieve maximum performance, the upconverted emission peak of the UCNPs and absorption band of the photosensitizers need to overlap significantly. However, the spectral mismatch between the upconverted emission maximum of UCNPs (predominantly in the green) and absorption maximum of most available photosensitizers (in the red) greatly limits the therapeutic efficacy of current UCNP-PDT platforms. Here we report a UCNP-PDT platform that under biobenign 808 nm NIR excitation shows a strong spectral overlap between the UCNP emission (λ em ) and absorption of zinc phthalocyanine photosensitizers (λ abs ). The spectrally matched UCNP red emission band is 40 times stronger than the green emission band and is independent of laser excitation power across a wide range (0.6–3.4 W/cm 2 ) applicable in biological systems. The spectrally matched UCNP-PDT platform enables rapid generation (5 min) of cytotoxic singlet oxygen via near-infrared excitation at extremely low laser power density of only 0.6 W/cm 2 . Finally, we show that the actively growing HeLa cancer cell spheroids with 3 mm diameter can be effectively suppressed with 65% drop of the cell viability, demonstrating the suitability and effectiveness of the spectrally matched UCNP-PDT platforms for cancer therapeutics.