Effect of avidin protein coated and uncoated mesoporous silica drug nanocarriers on their bioresponse in the lung

Mesoporous silica nanoparticles (MSNs) are novel drug carriers that offer unique properties, such as selective functionalization at specific sites within the nanoparticle. For example, as previously shown by us, the pores of the MSN particles can be functionalized by protease-responsive avidin caps. Here, we investigate the bioresponse of these MSN particles in the lung. For that, we instilled single-high doses (20 or 100 µg) of protein-coated MSN particles in BALB/c mice and studied their bioresponse after 1, 3 and 7 days. To analyze the effect of the protein coating, we also included non-functionalized MSNs in the study. Fluorescent labeling allowed for particle tracking in lung cryo-sections and cytospins of bronchoalveolar lavage (BAL) recovered cells. In this study, we show by confocal microscopy of lung- cryo sections, that instilled MSNs show widespread distribution over the alveolar surface of the lungs and are ineffectively cleared from there; after 7 days still many particles were observed. A typical acute inflammatory response was detected in response to high doses (100 µg) of avidin coated MSNs, however this resolved within 1 day. In addition, no inflammatory response was detected for the lower dose of 20 µg. Of note, exposure to non-functionalized MSNs indicated a toxic response as PMN/macrophage ratio and numbers of multinucleated macrophages were clearly increased. Our results indicate that avidin- protein coated MSNs are safe for the lung with regard to acute inflammatory responses. In addition, their long retention time and deep lung penetration offers potential for their application as therapeutic drug cargos in chronic lung disease.