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.

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Background Current conceptual models of health literacy (HL) illustrate the link between HL and health outcomes. However, these models fail to recognize and integrate certain elements of disease management, health system factors, and socio-demographic factors into their framework. This article outlines the development of Chronic Airway Disease (CAD) Management and Health Literacy (CADMaHL) conceptual model that integrates the aforementioned elements and factors into a single framework. Methods Information obtained during the following stages informed the development of our model: (1) a systematic review of existing CAD HL measurement tools that apply core HL domains; (2) patient-oriented focus group sessions to understand HL barriers to CAD self-management practices; (3) key-informant interviews to obtain potential strategies to mitigate CAD management barriers, and validate disease self-management topics; (4) elicited the perspectives of Canadian respirologist’s on the ideal functional HL skills for asthma and COPD patients. Results Throughout the study process many stakeholders (i.e., patients, key-informants, and an international HL advisory panel) contributed to and reviewed the model. The process enabled us to organize the CADMaHL model into 6 primary modules, including: INPUT, consisting of four HL core components (access, understand, communicate, evaluate,) and numeracy skills; OUTPUT, including application of the obtained information; OUTCOME, covering patient empowerment in performing self-management practices by applying HL skills; ASSESSMENT, consisting of information about functionality and relevancy of CADMaHL; IMPACT, including mediators between HL and health outcomes; CROSSCUTTING FACTORS, consisting of diverse socio-demographics and health-system factors with applicability across the HL domains. Conclusions We developed the CADMaHL model, with input from key-stakeholders, which addresses a knowledge gap by integrating various disease management, health-system and socio-demographic factors absent from previous published frameworks. We anticipate that our model will serve as the backbone for the development of a comprehensive HL measurement tool, which may be utilized for future HL interventions for CAD patients. Trial registration NCT01474928- Date of registration: 11/26/2017.