Polymer-coated hexagonal upconverting nanoparticles: chemical stability and cytotoxicity

Abstract

Large (120 nm) hexagonal NaYF4:Yb, Er nanoparticles (UCNPs) were synthesized by high-temperature coprecipitation method and coated with poly(ethylene glycol)-alendronate (PEG-Ale), poly (N,N-dimethylacrylamide-co-2-aminoethylacrylamide)-alendronate (PDMA-Ale) or poly(methyl vinyl ether-co-maleic acid) (PMVEMA). The colloidal stability of polymer-coated UCNPs in water, PBS and DMEM medium was investigated by dynamic light scattering; UCNP@PMVEMA particles showed the best stability in PBS. Dissolution of the particles in water, PBS, DMEM and artificial lysosomal fluid (ALF) determined by potentiometric measurements showed that all particles were relatively chemically stable in DMEM. The UCNP@Ale-PEG and UCNP@Ale-PDMA particles were the least soluble in water and ALF, while the UCNP@PMVEMA particles were the most chemically stable in PBS. Green fluorescence of FITC-Ale-modified UCNPs was observed inside the cells, demonstrating successful internalization of particles into cells. The highest uptake was observed for neat UCNPs, followed by UCNP@Ale-PDMA and UCNP@PMVEMA. Viability of C6 cells and rat mesenchymal stem cells (rMSCs) growing in the presence of UCNPs was monitored by Alamar Blue assay. Culturing with UCNPs for 24 h did not affect cell viability. Prolonged incubation with particles for 72 h reduced cell viability to 40%–85% depending on the type of coating and nanoparticle concentration. The greatest decrease in cell viability was observed in cells cultured with neat UCNPs and UCNP@PMVEMA particles. Thanks to high upconversion luminescence, high cellular uptake and low toxicity, PDMA-coated hexagonal UCNPs may find future applications in cancer therapy.

Toxicity of Large and Small Surface-Engineered Upconverting Nanoparticles for In Vitro and In Vivo Bioapplications

“…On the other hand, the leaches from L-UCNPs did not affect rMSC proliferation (Figure 4c); however, C6 growth was slowed down after the incubation with L-UCNP leaches for 72 h (p = 0.0086), L-UCNP@PMVEMA leaches (p = 0.0129), and L-UCNP@Ale-(PDMA-AEA) leaches (p = 0.0086), except for L-UCNP@Ale-PEG leaches, where the cell proliferation decreased only marginally (Figure 4d). Thus, it can be concluded that the real-time proliferation assay in cells incubated with UCNPs gave similar results to the MTT or Alamar blue assay performed in previous experiments [40,41], while the leaches, especially from L-UCNPs, were less harmful. In general, L-UCNPs were less toxic than S-UCNPs due to the lower surface-to-volume ratio.…”

“…This work is a continuation of our previous papers, in which we investigated the design and properties of small and large surface-engineered UCNPs with emphasis on their colloidal and chemical stability [39][40][41]. In this report, we compared the two types of UCNPs, small spherical (S-UCNPs) and large hexagonal (L-UCNPs), prepared by hightemperature coprecipitation of the respective lanthanide chlorides depending on the reaction conditions (Figure 1), in terms of morphology, cytotoxicity, and detection of DNA damage by the comet assay.…”

“…The resulting D h values of L-UCNP, L-UCNP@Ale-PEG, L-UCNP@Ale(PDMA-AEA), and L-UCNP@PMVEMA nanoparticles were 174, 158, 160, and 234 nm, respectively, and the corresponding ζ-potential was 28, 4, 22, and −46 mV, respectively (Table 1). Monitoring the fluoride ions dissolved in media in which the particles were aged showed that their degradation depended on many parameters, including size, coating type, temperature, and the medium used [40,41]. When released, Ln 3+ and F − ions engage with cellular phosphates found in membranes, ATP, and nucleic acids, resulting in cell damage.…”

“…Cell proliferation curves were determined after incubation with both particle types and their leaches (Figures 3 and 4). Particles were used at a concentration of 20 µg/mL, at which the viability of C6 and rMSCs in previous experiments using the Alamar blue or MTT assay reached >80% [40,41]. The growth of healthy non-tumor rMSCs incubated with any type of UCNPs for 1 day was similar, to the control.…”

“…The effect of coating on reducing UCNP cytotoxicity has already been reviewed [41]. This publication showed that uncoated nanoparticles had a substantial effect on cell viability.…”