Knock-out mouse models and single particle ICP-MS reveal that SP-D and SP-A deficiency reduces agglomeration of inhaled gold nanoparticles in vivo without significant changes to overall lung clearance.

IF 3.6 3区 医学 Q3 NANOSCIENCE & NANOTECHNOLOGY Nanotoxicology Pub Date : 2025-02-01 Epub Date: 2025-01-27 DOI:10.1080/17435390.2025.2454969
Adam Laycock, Artur Kirjakulov, Matthew Darren Wright, Konstantinos Nikolaos Bourdakos, Sumeet Mahajan, Howard Clark, Mark Griffiths, Grith Lykke Sørensen, Uffe Holmskov, Chang Guo, Martin O Leonard, Rachel Smith, Jens Madsen
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Abstract

The role of surfactant proteins A and D (SP-A and SP-D) in lung clearance and translocation to secondary organs of inhaled nanoparticles was investigated by exposing SP-A and SP-D knockout (AKO and DKO) and wild type (WT) mice nose-only for 3 hours to an aerosol of 20 nm gold nanoparticles (AuNPs). Animals were euthanised at 0-, 1-, 7- and 28-days post-exposure. Analysis by inductively coupled plasma mass spectrometry (ICP-MS) of the liver and kidneys showed that extrapulmonary translocation was below the limits of detection. Imaging of the lungs by laser ablation ICP-MS confirmed the homogenous distribution of AuNPs. Coherent anti-Stokes Raman Scattering, Second Harmonic Generation and Two-Photon Fluorescence imaging were applied for semi-quantitative analysis of the uptake of AuNPs by alveolar macrophages and found uptake increased with time post-exposure, peaking after 7 days, and with the largest increase in uptake being in WT mice. Single particle ICP-MS allowed particle counting and sizing of AuNPs in the lungs showing that particle agglomeration following deposition within the lung was greater for the wildtype than the knockout models, indicating a role for SP-A and SP-D in agglomeration, however, any effect of this on overall lung clearance was minimal. For all groups, the Au (mass) lung burden initial clearance half-time was approximately 20-25 d, however, the AuNP (particle number) lung burden clearance half-time was shorter at approximately 10 days. In general terms, differences between the results for the three models were limited, indicating the preferential clearance of smaller particles from the lung.

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来源期刊
Nanotoxicology
Nanotoxicology 医学-毒理学
CiteScore
10.10
自引率
4.00%
发文量
45
审稿时长
3.5 months
期刊介绍: Nanotoxicology invites contributions addressing research relating to the potential for human and environmental exposure, hazard and risk associated with the use and development of nano-structured materials. In this context, the term nano-structured materials has a broad definition, including ‘materials with at least one dimension in the nanometer size range’. These nanomaterials range from nanoparticles and nanomedicines, to nano-surfaces of larger materials and composite materials. The range of nanomaterials in use and under development is extremely diverse, so this journal includes a range of materials generated for purposeful delivery into the body (food, medicines, diagnostics and prosthetics), to consumer products (e.g. paints, cosmetics, electronics and clothing), and particles designed for environmental applications (e.g. remediation). It is the nano-size range if these materials which unifies them and defines the scope of Nanotoxicology . While the term ‘toxicology’ indicates risk, the journal Nanotoxicology also aims to encompass studies that enhance safety during the production, use and disposal of nanomaterials. Well-controlled studies demonstrating a lack of exposure, hazard or risk associated with nanomaterials, or studies aiming to improve biocompatibility are welcomed and encouraged, as such studies will lead to an advancement of nanotechnology. Furthermore, many nanoparticles are developed with the intention to improve human health (e.g. antimicrobial agents), and again, such articles are encouraged. In order to promote quality, Nanotoxicology will prioritise publications that have demonstrated characterisation of the nanomaterials investigated.
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