Ultraviolet phototoxicity of upconversion nanoparticles illuminated with near-infrared light

Abstract

Recently introduced upconversion nanoparticles (UCNPs) have pushed the depth of photodynamic therapy (PDT) treatment to the centimetre range by converting deeply-penetrating near-infrared (NIR) radiation to visible radiation for photoexcitation of PDT drugs. Here we demonstrate that the direct exposure of the cancer tissue to phototoxic ultraviolet radiation generated by NIR-photoexcited UCNPs enabled successful PDT. To this aim, core/shell UCNPs of the formula NaYF:YbTm/NaYF featuring an enhanced band in the ultraviolet UV-A and UV-B spectral bands were rationally designed and synthesised. Coupling UCNPs to the recombinant modules of the Designed Ankyrin Repeat Protein (DARPin) fused to a fluorescent protein mCherry allowed the target delivery of DARPin-mCherry/UCNP to human breast adenocarcinoma SK-BR-3 cells overexpressing HER2/neu receptors, as confirmed by fluorescence microscopy. DARPin-mCherry/UCNPs were demonstrated to be phototoxic to SK-BR-3 cells under 975 nm laser irradiation at a dose of 900 J cm due to the UV photoexcitation of endogenous photosensitizers and concomitant generation of reactive oxygen species. The Lewis lung cancer mouse model was employed to demonstrate the feasibility of PDT using UCNP-mediated UV excitation of endogenous photosensitizers in the tumor tissue at a NIR dose of 1200 J cm. This study paves the way for exploring and harnessing UV photoexcitation processes in deep tissues in vivo.

DARPins: Promising Scaffolds for Theranostics

“…In animal models, far-red fluorescent proteins, such as mCherry, can be applied to allow intravital visualization of a tumor [38]. Cherry and HER2-specific DARPin 9_29 were fused to obtain the recombinant protein DARPin-mCherry, which specifically stains HER2positive cancer cells [39] and is used for the functionalization of nanoparticles [40][41][42][43] as described below.…”

“…DARPin 9_29 was used to deliver upconverting nanoparticles into a tumor during photodynamic therapy. NaYF 4 : Yb 3 + Tm 3 + / NaYF 4 particles emitting ultraviolet radiation when exposed to infrared light were coated with the DARPin-mCherry protein [39], which allows visualization of cancer cells thanks to the far-red fluorescent mCherry module [40]. DARPin 9_29 and the DARPin-mCherry protein containing it were also used to coat 5-nm gold nanoparticles [41] and gold nanorods [42].…”

“…The resulting nanoparticles were used to visualize breast tumors in a xenograft mouse model and exhibited low side toxicity in vivo [84]. The same conjugation method was applied to functionalize upconverting nanoparticles with the DARPin-mCherry protein [43]. DARPin-PE40 was coupled with upconverting radioactive nanoparticles in the same way, making it possible to visualize tumors in vivo and efficiently eliminate HER2-overexpressing cells both in vitro and in vivo [85].…”

The Role of Interleukin-37 in the Pathogenesis of Allergic Diseases

“…Two isoforms, IL-37d and IL-37e, are expressed exclusively in the bone marrow and testes [25,26]. Mature IL-37 and its proform are secreted by activated macrophages, dendritic cells (DC), and peripheral blood mononuclear cells (PBMCs) [40]. IL-37, which is secreted by these cells, exerts its biological effects via a unique receptor complex.…”

“…IL-18 is one of the key pro-inflammatory cytokines acting as a pathogenetic factor in a number of diseases [41,42]. The IL-18 receptor complex consists of two chains: α (IL-18Rα) and β (IL-18Rβ), each of which has a TIR domain [43]. During the formation of the IL-18Rα/IL-18/IL-18Rβ complex, the TIR domains come together, after which the MyD88 factor binds to them and induces the pro-inflammatory effect (Fig.…”