Effect of different silica coatings on the toxicity of upconversion nanoparticles on RAW 264.7 macrophage cells

Abstract

Upconversion nanoparticles (UCNPs), consisting of NaYF4 doped with 18% Yb and 2% Er, were coated with microporous silica shells with thickness values of 7 ± 2 and 21 ± 3 nm. Subsequently, the negatively charged particles were functionalized with N-(6-aminohexyl)-3-aminopropyltrimethoxysilane (AHAPS), which provide a positive charge to the nanoparticle surface. Inductively coupled plasma optical emission spectrometry (ICP-OES) measurements revealed that, over the course of 24h, particles with thicker shells release fewer lanthanide ions than particles with thinner shells. However, even a 21 ± 3 nm thick silica layer does not entirely block the disintegration process of the UCNPs. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays and cell cytometry measurements performed on macrophages (RAW 264.7 cells) indicate that cells treated with amino-functionalized particles with a thicker silica shell have a higher viability than those incubated with UCNPs with a thinner silica shell, even if more particles with a thicker shell are taken up. This effect is less significant for negatively charged particles. Cell cycle analyses with amino-functionalized particles also confirm that thicker silica shells reduce cytotoxicity. Thus, growing silica shells to a sufficient thickness is a simple approach to minimize the cytotoxicity of UCNPs.

Stability, dissolution, and cytotoxicity of NaYF4-upconversion nanoparticles with different coatings

“…6 b). This is in accordance with the lower toxicity of UCNPs with thicker silica shells as compared to those with thinner silica shells previously reported by Kembuan et al 12 for macrophages (RAW 264.7 cells).

Figure 6 Viability of HaCaT cells exposed to ( a ) UC-SiO 2 -thick and UC-SiO 2 -thin for 24 h and 48 h; and ( b ) UC-bare-20 (BF 4 ) and UC-SiO 2 -thick after 72 h of aging in di-H 2 O and DMEM.

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“…Despite the large number of advantages of UCNPs and possible biomedical applications, concerns about their biosafety and potential adverse effects have been raised 12 , 13 , as the dissolution of NaYF 4 UCNPs in aqueous media can result in the release of fluoride and lanthanide ions which can induce cytotoxicity in biological systems 14 – 18 , particularly under high dilution conditions in aqueous media 11 , 14 , 15 , 19 . Surface modification with various ligands has been used not only to tune the dispersibility and colloidal stability of NaYF 4 UCNPs, but also to reduce their dissolution in aqueous environments, as the release of fluoride and lanthanide ions may induce cytotoxicity in biological systems 14 – 18 , 20 .…”

Initial Biological Assessment of Upconversion Nanohybrids

“…The viability assays based on dehydrogenase detection (MTT and MTS assay) indicated that UC n induced greater effects than UC@CB [7]. Higher cytotoxicity was also reported previously for uncoated UCNPs when compared to silica-coated ones in RAW 264.7 cells and was attributed to higher internalization of negatively charged uncoated UCNPs [25]. Similarly, our results also indicate that a particle concentration up to 12.5 µg/mL does not lead to a critical cell line viability.…”

“…Nevertheless, cytotoxicity on HeLa and RAW 267.4 depended on the UCNPs tested. UC n and UC@CB [7] showed moderate and low cytotoxicity, respectively, in macrophages in a similar trend to that observed by Kembuan et al [25], indicating the enhancement of the biocompatibility of UCNPs nanoparticles upon cucurbit [7]uril coating. UC n and UC@CB [7] showed very low cytotoxicity on HeLa; see Figure 3.…”

“…RAW 264.7 is an established model for macrophages that actively and rapidly take up nanomaterials from biological media. This model has already been applied in studies involving bare NaGdF 4 [24] and silica-coated UCNPs [25]. O (>99.9%, all of them)), 1-octadecene (95%), oleic acid (99.9%), NaOH, NH 4 F (99.99%), and cucurbit [7]uril were purchased from Sigma-Aldrich (Madrid, Spain) and used as received without previous purification.…”