Behavior and effect of nanoparticles on neutrophil recruitment in the pulmonary microcirculation

Abstract

<b>Background:</b> Different surface-modified nanoparticles, including Quantum dots (QDs) which exhibit unique fluorescent properties ideally for novel imaging approaches, are intended to be used for pulmonary biomedical applications. However, the behavior of QDs in the pulmonary microcirculation and their impact on immune cells under pathophysiologic conditions such as ALI and IPF, are still largely unknown. <b>Aims:</b> We hypothesize that the surface-modification of QDs determines their biological interactions and pro-inflammatory potential. Therefore, we aim to analyze i) QDs interactions and ii) neutrophil responses in murine models of ALI and IPF. <b>Methods:</b> Amine or carboxyl surface-modification QDs (aQDs, cQDs) (1pmol/g) were intravenously applied to healthy, LPS or Bleomycin treated mice. We performed lung intra-vital microscopy to investigate QDs dynamics and their impact on neutrophil recruitment during ALI and IPF in real time. <b>Results:</b> In healthy mice, aQDs elicited a significant increase (2.6 ± 0.4-fold) in neutrophil numbers in alveolar microvessels over 60 min as compared to the control group (1.3 ± 0.1-fold), while cQDs induced slight neutrophil increment (1.9 ± 0.2-fold). Similarly, in the ALI group, 60 min after aQDs application, neutrophil numbers were significantly higher (3.6 ± 0.3-fold) than the control group (2.9 ± 0.4-fold). In the IPF group, also aQDs treatment increased the neutrophil level (2.5 ± 0.1-fold) compared to bleomycin control group (1.8 ± 0.3-fold). However, cQDs had no additional effect on neutrophil numbers in ALI or IPF mice. <b>Conclusions:</b> Compared to aQDs, cQDs did not enhance the disease dependent microvascular inflammation.