Abstract

Nanoparticles for medical use should be non-cytotoxic and free of bacterial contamination. Upconversion nanoparticles (UCNPs) coated with cucurbit[7]uril (CB[7]) made by combining UCNPs free of oleic acid, here termed bare UCNPs (UCn), and CB[7], i.e., UC@CB[7] nanohybrids, could be used as photoactive inorganic-organic hybrid scaffolds for biological applications. UCNPs, in general, are not considered to be highly toxic materials, but the release of fluorides and lanthanides upon their dissolution may cause cytotoxicity. To identify potential adverse effects of the nanoparticles, dehydrogenase activity of endothelial cells, exposed to various concentrations of the UCNPs, was determined. Data were verified by measuring lactate dehydrogenase release as the indicator of loss of plasma membrane integrity, which indicates necrotic cell death. This assay, in combination with calcein AM/Ethidium homodimer-1 staining, identified induction of apoptosis as main mode of cell death for both particles. The data showed that the UCNPs are not cytotoxic to endothelial cells, and the samples did not contain endotoxin contamination. Higher cytotoxicity, however, was seen in HeLa and RAW 264.7 cells. This may be explained by differences in lysosome content and particle uptake rate. Internalization of UCn and UC@CB[7] nanohybrids by cells was demonstrated by NIR laser scanning microscopy.

Highlights

  • The combination of macrocyclic hosts and photoactive inorganic nanomaterials allows for the design of new functional photoactive inorganic–organic hybrid nanomaterials that benefit from the properties of the individual counterparts [1]

  • Oleate-capped upconversion nanoparticles (UCNPs) were synthesized by the high-temperature co-precipitation method [8]

  • The bare UCNPs were stable and no hydrolysis, corrosion, and aggregation were observed under mild acidic conditions [31,32]

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Summary

Introduction

The combination of macrocyclic hosts and photoactive inorganic nanomaterials allows for the design of new functional photoactive inorganic–organic hybrid nanomaterials that benefit from the properties of the individual counterparts [1]. Our interest in this communication focuses on photoactive nanohybrids which combine recognition based on host–guest chemistry and the unique photophysical properties of photoactive nanoparticles [2] Macrocycles, such as crown ether, cyclodextrins, calixarenes, cucurbiturils, and pillarenes, do confer hydrophilicity to the resulting nanohybrids, and preserve their supramolecular recognition capacity for subsequent self-assembly when acting as surface capping agents for photoactive inorganic nanoparticles [2]. These nanohybrids could be used as stimuli-responsive smart nanocarriers to deliver a selected encapsulated cargo [3,4]. UCNPs are composed of an inorganic matrix doped with photoactive lanthanide cations that can be excited with low-energy near-infrared (NIR) photons (two or more) and emit at shorter wavelengths (ultraviolet, visible light, and NIR), giving rise to anti-Stokes emission and highly

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