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

Abstract

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 (λem) and absorption of zinc phthalocyanine photosensitizers (λabs). 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/cm2) 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/cm2. 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.

NIR-Light-Driven Generation of Reactive Oxygen Species Using Ru(II)-Decorated Lipid-Encapsulated Upconverting Nanoparticles

“…43,44 In most cases, however, green- or red-light-absorbing PDT dyes are employed, e.g., chlorin-e6, zinc phthalocyanine, or rose bengal, combined with the green and red emission of Er-doped UCNPs. 45−47 Although some Tm-doped UCNP-PDT systems have been reported, e.g., using riboflavin or fullerenes as the photosensitizer, 48,49 to the best of our knowledge, no metal-based PDT photosensitizers have been used in combination with UCNPs. On the other hand, some groups have recently shown that ligand-photodissociation reactions in ruthenium polypyridyl complexes can be triggered by a combination of UCNPs and 980 nm light, thus providing an important proof of concept for UCNP-mediated PACT.…”

Recent progress in the development of upconversion nanomaterials in bioimaging and disease treatment

“…UCNP synthesized by the thermal decomposition method can also be applied to multi-functional application platforms. He et al prepared UCNP with excellent emission wavelength by thermal decomposition method and loaded with photosensitizer for photodynamic therapy of three-dimensional (3D) HeLa cell spheroids [ 68 ]. The multifunctional PDT platform has been evaluated to confirm the feasibility of widely biomedical applications.…”

Near-Infrared Light-Triggered Photodynamic Therapy and Apoptosis Using Upconversion Nanoparticles With Dual Photosensitizers

“…The hydrophobic UCNPs were encapsulated by DSPE-PEG through a hydrophobic interaction between the surface oleic acid and DSPE. The hydrophobic photosensitizers, Ce6 and RB, were also loaded in the hydrophobic layer (He et al, 2018).…”