Investigating the influence of particle hydrophobicity on lung deposition using nonionic dye partitioning

The regional deposition of inhaled particulate matter (PM) in the respiratory tract determines its biological fate and lung toxicity. While it is widely accepted that the size of PM plays a predominant role in affecting lung deposition, the impact of other physicochemical properties, especially hydrophobicity, remains unclear. This knowledge gap exists, in part, due to the absence of standard methods to characterize the hydrophobicity of PM. Here, we developed a novel nonionic dye partitioning method to quantitatively characterize the hydrophobicity of PM. The use of a nonionic dye, rhodamine B, effectively eliminates experimental artifacts arising from unwanted dye adsorption due to electrostatic interactions, thus significantly improving the accuracy and applicability of the method. Through an intranasal mouse exposure model, we discovered that the lung deposition of four types of PM originated from common anthropogenic sources, including PM2.5, dust, biochar, and carbon black, is mediated by their hydrophobicity. The most hydrophobic PM tends to be trapped in the nasal cavity, whereas the least hydrophobic PM penetrates deep into the alveoli, inducing severe lung inflammation. The hydrophobicity-dependent deposition of PM in the respiratory tract offers novel insights into understanding the acute lung toxicity of inhaled PM and provides a foundation for the design of safer and more efficacious inhalable medicines. Furthermore, the nonionic dye partitioning method shows promise as a user-friendly and cost-effective approach for characterizing the hydrophobicity of PM.