title: Applicability of avidin protein coated mesoporous silica nanoparticles as drug carriers in the lung.
abstract: Mesoporous silica nanoparticles (MSNs) exhibit unique drug delivery properties and are thus considered as promising candidates for next generation nano-medicines. In particular, inhalation into the lungs represents a direct, non-invasive delivery route for treating lung disease. To assess MSN biocompatibility in the lung, we investigated the bioresponse of avidin-coated MSNs (MSN-AVI), as well as aminated (uncoated) MSNs, after direct application into the lungs of mice. We quantified MSN distribution, clearance rate, cell-specific uptake, and inflammatory responses to MSNs within one week after instillation. We show that amine-functionalized (MSN-NH2) particles are not taken up by lung epithelial cells, but induced a prolonged inflammatory response in the lung and macrophage cell death. In contrast, MSN-AVI co-localized with alveolar epithelial type 1 and type 2 cells in the lung in the absence of sustained inflammatory responses or cell death, and showed preferential epithelial cell uptake in in vitro co-cultures. Further, MSN-AVI particles demonstrated uniform particle distribution in mouse lungs and slow clearance rates. Thus, we provide evidence that avidin functionalized MSNs (MSN-AVI) have the potential to serve as versatile biocompatible drug carriers for lung-specific drug delivery.
authors.affiliation: Comprehensive Pneumology Center (CPC), University Hospital, Ludwig-Maximilians University and Helmholtz Zentrum München, Munich, Germany. sabine.vanrijt@helmholtz-muenchen.de.
authors.forename: S H
authors.initials: SH
authors.lastname: van Rijt
authors.affiliation: Comprehensive Pneumology Center (CPC), University Hospital, Ludwig-Maximilians University and Helmholtz Zentrum München, Munich, Germany. sabine.vanrijt@helmholtz-muenchen.de.
authors.forename: D A
authors.initials: DA
authors.lastname: Bölükbas
authors.affiliation: Department of Chemistry and Center for NanoScience (CeNS), University of Munich (LMU), Butenandtstrasse 5-13(E), 81377 Munich, Germany. bein@lmu.de.
authors.forename: C
authors.initials: C
authors.lastname: Argyo
authors.affiliation: Comprehensive Pneumology Center (CPC), University Hospital, Ludwig-Maximilians University and Helmholtz Zentrum München, Munich, Germany. sabine.vanrijt@helmholtz-muenchen.de.
authors.forename: K
authors.initials: K
authors.lastname: Wipplinger
authors.affiliation: Comprehensive Pneumology Center (CPC), University Hospital, Ludwig-Maximilians University and Helmholtz Zentrum München, Munich, Germany. sabine.vanrijt@helmholtz-muenchen.de.
authors.forename: M
authors.initials: M
authors.lastname: Naureen
authors.affiliation: Department of Chemistry and Center for NanoScience (CeNS), University of Munich (LMU), Butenandtstrasse 5-13(E), 81377 Munich, Germany. bein@lmu.de.
authors.forename: S
authors.initials: S
authors.lastname: Datz
authors.affiliation: Comprehensive Pneumology Center (CPC), University Hospital, Ludwig-Maximilians University and Helmholtz Zentrum München, Munich, Germany. sabine.vanrijt@helmholtz-muenchen.de.
authors.forename: O
authors.initials: O
authors.lastname: Eickelberg
authors.affiliation: Comprehensive Pneumology Center (CPC), University Hospital, Ludwig-Maximilians University and Helmholtz Zentrum München, Munich, Germany. sabine.vanrijt@helmholtz-muenchen.de.
authors.forename: S
authors.initials: S
authors.lastname: Meiners
authors.affiliation: Department of Chemistry and Center for NanoScience (CeNS), University of Munich (LMU), Butenandtstrasse 5-13(E), 81377 Munich, Germany. bein@lmu.de.
authors.forename: T
authors.initials: T
authors.lastname: Bein
authors.affiliation: Comprehensive Pneumology Center (CPC), University Hospital, Ludwig-Maximilians University and Helmholtz Zentrum München, Munich, Germany. sabine.vanrijt@helmholtz-muenchen.de.
authors.forename: O
authors.initials: O
authors.lastname: Schmid
authors.affiliation: Comprehensive Pneumology Center (CPC), University Hospital, Ludwig-Maximilians University and Helmholtz Zentrum München, Munich, Germany. sabine.vanrijt@helmholtz-muenchen.de.
authors.forename: T
authors.initials: T
authors.lastname: Stoeger
mesh_terms: D000818:Animals; D001360:Avidin; D002460:Cell Line; D018920:Coculture Techniques; D016207:Cytokines / Q000378:metabolism; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D005260:Female; D018836:Inflammation Mediators / Q000378:metabolism; D008168:Lung / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D050997:Nanomedicine; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity; D012822:Silicon Dioxide
chemical_list: D016207:Cytokines; D004337:Drug Carriers; D018836:Inflammation Mediators; D001360:Avidin; D012822:Silicon Dioxide