PT  - JOURNAL ARTICLE
AU  - Emanuela Cova
AU  - Gabriele Ceccarelli
AU  - Laura Pandolfi
AU  - Manuela Agozzino
AU  - Raffaele Allevi
AU  - Laura Benedetti
AU  - Miriam Colombo
AU  - Simona Inghilleri
AU  - Sara Magni
AU  - Tiberio Oggionni
AU  - Davide Prosperi
AU  - Maria Gabriella Cusella
AU  - Federica Meloni
TI  - Engineered gold nanoparticles targeted to mesenchymal cells from BOS patients can be safely administered to normal mice by inhalation
AID  - 10.1183/13993003.congress-2015.PA1793
DP  - 2015 Sep 01
TA  - European Respiratory Journal
PG  - PA1793
VI  - 46
IP  - suppl 59
4099  - http://erj.ersjournals.com/content/46/suppl_59/PA1793.short
4100  - http://erj.ersjournals.com/content/46/suppl_59/PA1793.full
SO  - Eur Respir J2015 Sep 01; 46
AB  - Engineered gold nanoparticles targeted with a specific antibody (GNP-HCe) to primary lung mesenchymal cells (MC) isolated from BOS patients and loaded with everolimus were able to specifically inhibit MC proliferation and increase apoptosis without stimulating the inflammatory response (Cova, 2014). The aim of the present work was to prove that GNP-HCe can be safely administered to mice by inhalation.Nanoparticles (NPs) distribution and toxicity in vivo were assayed by aerosolization of 50 µg of labeled GNP-HCe or GNP-HC (gold nanoparticles with the antibody without everolimus) for 30 min a day for 2 weeks. Control mice were treated with saline solution. NPs localization was evaluated in lungs, kidney, spleen and liver by near-infrared (NIR) light imaging technology. Electron microscopy analysis (TEM) was performed to assess NP lung distribution. Toxic effects on tissue were evaluated by hystology. Inflammation burst in lung was tested by IL-8-homologue, CXCL1/KC, in BAL by ELISANIR showed that fluorescence was significantly higher (p<0,001) in lung compared to untreated mice and was not present in spleen, kidney and liver. As evidenced by TEM, NPs in lungs were localized in macrophages but not into epithelial cells. Morphologic alterations were not observed in lung, kidney, spleen and liver. KC secretion did not significantly increase after NP inhalation (p=0,05)Our data showed that NPs were not taken by epithelial cells and were not toxic for other organs. Moreover, their presence did not stimulate the local inflammatory response. This work confirms the feasibility of GNP-HCe to be used as novel therapeutic approach for patients affected by CLAD.