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

Area of Science:

• Nanotechnology
• Biomaterials Science
• Cell Biology

Background:

• Upconversion nanoparticles (UCNPs) are promising for biomedical applications.
• Surface modification of UCNPs is crucial for improving biocompatibility and cellular interactions.
• Understanding nanoparticle toxicity and biodistribution is essential for in vivo applications.

Purpose of the Study:

• To synthesize and characterize polymer-coated NaYF4:Yb,Er upconversion nanoparticles (UCNPs) of different sizes.
• To evaluate the cellular internalization, cytotoxicity, and oxidative damage of these UCNPs in rat mesenchymal stem cells (rMSCs) and C6 cancer cells.
• To investigate the in vivo biodistribution and elimination pathways of UCNPs in mice.

Main Methods:

• High-temperature coprecipitation synthesis of spherical/hexagonal NaYF4:Yb,Er UCNPs (25 nm S-UCNPs, 120 nm L-UCNPs).
• Surface modification with poly(ethylene glycol) (PEG), poly(N,N-dimethylacrylamide-co-2-aminoethylacrylamide) [P(DMA-AEA)] with alendronate, and poly(methyl vinyl ether-co-maleic acid) (PMVEMA).
• Cellular internalization via electron microscopy, cytotoxicity via real-time proliferation assay, oxidative damage via comet assay, and in vivo studies in mice.

Main Results:

• Both L- and S-UCNPs were internalized by rMSCs and C6 cells via endosomes.
• L-UCNPs exhibited lower cytotoxicity than S-UCNPs across both cell types.
• Polymer coatings influenced cell viability, with S-UCNP@Ale-(PDMA-AEA) and S-UCNP@Ale-PEG showing higher viability than uncoated S-UCNPs.
• Neat L-UCNPs induced more oxidative damage in rMSCs than coated L-UCNPs; no significant difference was observed in C6 cells.
• In vivo studies showed L-UCNPs are eliminated via the hepatobiliary route, with L-UCNP@Ale-PEG showing significant liver elimination within 96 hours.

Conclusions:

• Larger UCNPs (L-UCNPs) demonstrate reduced toxicity and favorable hepatobiliary elimination.
• Surface modification with polymers, particularly alendronate-terminated P(DMA-AEA) and PEG, can mitigate UCNP cytotoxicity and oxidative stress.
• UCNP size and surface chemistry are critical factors determining their biological fate and safety for potential biomedical applications.