Evaluation of Lanthanide-Doped Upconverting Nanoparticles for in Vitro and in Vivo Applications

Abstract

Because of their unique physicochemical properties, lanthanide-doped upconverting nanoparticles (Ln-UCNPs) have exceptional potential for biological applications. However, the use in biological systems is hampered by the limited understanding of their bionano interactions. Our multidisciplinary study has generated these insights through in-depth and quantitative analyses. The Ln-UCNPs examined here are spherical, monodisperse, and stable in aqueous environments. We show that Ln-UCNPs were associated with HeLa (cervical cancer) and LLC-PK1 (renal proximal tubule) cells and were nontoxic over a wide concentration range. Multiple biomarkers were assessed to monitor the cellular homeostasis in Ln-UCNP-treated cells. To this end, we evaluated the nuclear lamina, nucleoli, and nuclear transport factors. Single-cell analyses quantified the impact on Nrf2 and NF-κB, two transcription factors that control stress and immune responses. Moreover, we measured Ln-UCNP-induced changes in the abundance of molecular chaperones. Collectively, in vitro studies confirmed that Ln-UCNPs are nontoxic and trigger minor cellular stress responses. This lack of toxicity was verified in vivo, using the model organism Caenorhabditis elegans. The compatibility with biological systems prompted us to assess Ln-UCNPs as potential contrast agents for magnetic resonance imaging. We demonstrated that the Ln-UCNPs examined here were especially suitable as T 2 contrast agents; they clearly outperformed the clinically used Gadovist. Taken together, our interdisciplinary work provides robust evidence for the nontoxicity of Ln-UCNPs. This sets the stage for the translation of Ln-UCNP for use in complex biological systems.

Polymer-Functionalized Upconversion Nanoparticles for Light/Imaging-Guided Drug Delivery

“…An amphiphilic block copolymer poly(oligo-(ethylene glycol) methyl ether acrylate)-block-poly-(monoacryloxy ethyl phosphate) (POEGA-b-PMAEP), which contained two C-PO-(OR) 2 groups, was used to coat NaGdF 4 / 49% Yb 3+ ,1% Tm 3+ /NaYF 4 UCNPs to form stable and monodispersed nanoparticles. 208 Treatment with UCNPs for 72 h with a concentration of 100 μg mL −1 did not cause any significant changes to the metabolic activities of HeLa (cervical cancer) and LLC-PK1 (renal proximal tubule) cells under irradiation of 980 nm laser (0.918 W/cm 2 ). Furthermore, sublethal effects such as stress responses or other changes in cell physiology were studied by quantifying the impact on the nuclear lamina, nucleoli, and Nrf2 and NF-κB, which are two nuclear transport factors that regulate the oxidative stress response.…”

“…Moreover, the in vivo model organism Caenorhabditis also verified the lack of toxicity of UCNPs. 208 8.4. Toxicity of PAA-Coated UCNPs.…”

Biomedical Applications of Lanthanide Nanomaterials, for Imaging, Sensing and Therapy

“…Dana M. et al tested their NaGdF4:Tm 3+ Yb 3+ nanoparticles on a variety of cancer cell lines and C.elegans. detected no toxicity over a wide concentration range [74]. For the same kind of particle, Huaiyong Xing et al showed after seven days post-injection to the mice, the NaGdF4:Tm 3+ ultra-small nanoparticle could be excreted into feces and urine [75].…”

Rare earth smart nanomaterials for bone tissue engineering and implantology: Advances, challenges, and prospects

“… 100 , 114 , 115 , 116 , 117 , 118 , 119 , 120 , 121 In this pipeline, the RE nanoparticles have tremendous potential for bone graft development since it has versatile bio applications, including an antioxidant to antimicrobial effect. 122 , 123 , 124 Furthermore, RE metals can be doped in the abovementioned nanoparticles to redevelop the smart nano‐biomaterials with improved antimicrobial, immunomodulatory potential of ceria, 125 , 126 the osteo‐angiogenic effect of europium, 127 , 128 , 129 contrast imaging potential of Gd, 130 , 131 and laser irradiation property of neodymium. 132 , 133 This review exemplifies the role of various RE nanomaterials for the therapeutic modulation of these important bone cells.…”