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Biocompatibility assessment of up- and down-converting nanoparticles: implications of interferences with in vitro assays

Efficacy, quality and safety assessment of nanoparticles (NPs) is crucial during their design and development for biomedicine. One of the prerequisite steps during this evaluation is in vitro testing that employs cell-based assays not always validated and well-adapted for NPs. Interferences with in vitro assays may arise due to the nano-related optical, oxidative, fluorescent, surface and catalytic properties of NPs. Thus, proper validation of each assay system has to be performed for each NP type. The unique up- and down-shifting nanoparticles (UCNPs and DSNPs, respectively) are one of the attractive NPs due to their photoluminescent properties that inspired many bioanalytical applications. Their long luminescence lifetimes and excellent photostability enable multiplexed detection in deep tissues, but translational gap between laboratory and clinics still exists due to safety concerns of therapeutic and diagnostic (“theranostic”) applications of such NPs. This study aimed to evaluate the applicability of the most common in vitro cytotoxicity assays for the safety assessment of up- and down-converting lanthanide-doped NPs. Conventional cell viability tests and fluorescence-based assays for oxidative stress response were selected to determine the biological effects of UCNPs and DSNPs to diverse human cells. Comparison was performed with known silver and iron oxide NPs for verification purposes. Both the plate reader and flow cytometric measurements were examined. The obtained results indicated that all types of NPs interfered to a much lesser extent than metallic NPs. In addition, the great potential of both UCNPs and DSNPs for biomedicine was manifested due to their biocompatibility and low toxicity. In addition, biological effects and toxicity of these NPs are tissue- and cell-dependent. Better and safer design of UCNPs and DSNPs for theranostic use should rely on integrative and interdisciplinary approach encompassing materials synthesis and research, detection instrumentation, biofunctionalization and bioassay development to toxicity testing.

photon upconversion and down-shifting, nanoparticles, interferences, biocompatibility, safety

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