Intrapulmonary Cellular-Level Distribution of Inhaled Nanoparticles with Defined Functional Groups and Its Correlations with Protein Corona and Inflammatory Response

Abstract

Concerns over the health risks associated with airborne exposure to ultrafine particles [PM0.1, or nanoparticles (NPs)] call for a comprehensive understanding in the interactions of inhaled NPs along their respiratory journey. We prepare a collection of polyethylene glycol-coated gold nanoparticles that bear defined functional groups commonly identified in atmospheric particulates (Au@PEG-X NPs, where X = OCH 3 , COOH, NH 2 , OH, or C 12 H 25 ). Regardless of the functional group, these ∼50 nm NPs remain colloidally stable following aerosolization and incubation in bronchoalveolar lavage fluid (BALF), without pronouncedly crossing the air−blood barrier. The type of BALF proteins adhered onto the NPs is similar, but the composition of protein corona depends on functional group. By subjecting Balb/c mice to inhalation of Au@PEG-X NPs for 6 h, we demonstrate that the intrapulmonary distribution of NPs among the various types of cells (both found in BALF and isolated from the lavaged lung) and the acute inflammatory responses induced by inhalation are sensitive to the functional group of NPs and postinhalation period (0, 24, or 48 h). By evaluating the pairwise correlations between the three variables of "lung−nano" interactions (protein corona, intrapulmonary cellularlevel distribution, and inflammatory response), we reveal strong statistical correlations between the (1) fractions of albumin or carbonyl reductase bound to NPs, (2) associations of inhaled NPs to neutrophils in BALF or macrophages in the lavaged lung, and (3) level of total protein in BALF. Our results provide insights into the effect of functional group on lung−nano interactions and health risks associated with inhalation of PM0.1.

Exposure to airborne gold nanoparticles: a review of current toxicological data on the respiratory tract

“…However, different preparations of AuNPs induced different degrees of inflammation, underlining the effect of surface functionality of NP inhaled on the triggered acute inflammatory response. Interestingly, in the only study in which in vivo results were compared to in vitro results, the amount of inflammatory markers was not coherent between two systems highlighting the importance of in vivo approaches (Yin et al 2019).…”

“…Concerning inhalation studies for the evaluation of AuNP-induced inflammation, Yin et al (2019) reported the interaction of sub-100 nm aerosolised NPs with the lungs at the cellular level and the inflammatory responses triggered by their inhalation. The authors characterised synthesised citrate-capped AuNPs and PEG-coated AuNPs with different functional groups both in water suspensions and in BAL by DLS, UV-vis, TEM and zeta potential.…”

Municipal Residence Level of Long-Term PM10 Exposure Associated with Obesity among Young Adults in Seoul, Korea

“…The particle constituents are known to be varied according to the fraction size of PM and the relation with health may vary [ 48 , 49 , 50 ]. Recently, ultrafine particles (PM 0.1 ) were explored and suggested for the inflammatory responses [ 51 ]. Although finer fractions of PM were not explored in this study, those finer particles such as PM 2.5 or PM 0.1 are subsets of PM 10.…”

Disentangling Biomolecular Corona Interactions With Cell Receptors and Implications for Targeting of Nanomedicines

“…The use of multiple cellular responses showed that different descriptors seem to be involved into different biological processes. Along these lines, a more complex correlation analysis involving three variables was also applied as another means of predicting nanoparticle-cell association (Yin et al, 2019): by adding the inflammatory response as another variable next to biomolecular corona composition and cellular uptake, Yin et al (2019) revealed a strong statistical correlation between the fractions of certain proteins bound to nanoparticles, the association after inhalation of these nanoparticles to immune cells in the lungs, and the total protein content in bronchoalveolar lavage fluid. A similar correlation analysis between corona composition and cellular uptake was performed by Ritz et al (2015).…”

“…Thus, with the benefits and limitations offered by the discussed methods, better insights could be achieved by, for instance, combining some of them on the same system. At the same time, the biomolecular corona itself can be used as a tool to discover potential ligands as well as receptors involved in nanoparticle uptake in specific cell types to be used for novel targeting strategies (Walkey et al, 2014;Liu et al, 2015;Ritz et al, 2015;Yin et al, 2019;Yang et al, 2020). Indeed, many more aspects are yet still to be disentangled, for instance, how other physiological factors such as flow and shear stress (in blood) influence not only the biomolecular corona composition, but also the resulting interactions with cell receptors.…”