BACKGROUND: Investigations on adverse biological effects of nanoparticles (NPs) in the lung by in vitro studies are usually performed under submerged conditions where NPs are suspended in cell culture media. However, the behaviour of nanoparticles such as agglomeration and sedimentation in such complex suspensions is difficult to control and hence the deposited cellular dose often remains unknown. Moreover, the cellular responses to NPs under submerged culture conditions might differ from those observed at physiological settings at the air-liquid interface. RESULTS: In order to avoid problems because of an altered behaviour of the nanoparticles in cell culture medium and to mimic a more realistic situation relevant for inhalation, @entity1 A549 lung epithelial cells were exposed to aerosols at the @entity11535 ( @entity11535 ) by using the @entity11535 deposition apparatus (ALIDA). The application of an electrostatic field allowed for particle deposition efficiencies that were higher by a factor of more than 20 compared to the unmodified VITROCELL deposition system. We studied two different amorphous @entity3440 nanoparticles (particles produced by flame synthesis and particles produced in suspension by the St  ber method). Aerosols with well-defined particle sizes and concentrations were generated by using a commercial electrospray generator or an atomizer. Only the electrospray method allowed for the generation of an aerosol containing monodisperse NPs. However, the deposited mass and surface dose of the particles was too low to induce cellular responses. Therefore, we generated the aerosol with an atomizer which supplied agglomerates and thus allowed a particle deposition with a three orders of magnitude higher mass and of surface doses on lung cells that induced significant biological effects. The deposited dose was estimated and independently validated by measurements using either transmission electron microscopy or, in case of labelled NPs, by fluorescence analyses. Surprisingly, cells exposed at the @entity11535 were less sensitive to @entity3440 NPs as evidenced by reduced @entity137 and inflammatory responses. CONCLUSION: Amorphous @entity3440 NPs induced qualitatively similar cellular responses under submerged conditions and at the @entity11535 . However, submerged exposure to NPs triggers stronger effects at much lower cellular doses. Hence, more studies are warranted to decipher whether cells at the @entity11535 are in general less vulnerable to NPs or specific NPs show different activities dependent on the exposure method.

@entity3440 nanoparticles are less toxic to XXXX lung cells when deposited at the air-liquid interface compared to conventional submerged exposure.

@entity1 :: ('9606', 'Species') :: ['human'] @entity137 :: ('MESH:D064420', 'Disease') :: ['cytotoxicity'] @entity11535 :: ('MESH:D009041', 'Disease') :: ['air-liquid interphase', 'ALI'] @entity3440 :: ('MESH:D012822', 'Chemical') :: ['silica']
@entity1 :: (9606,Species) :: ['human']
