title: Selective targeting of alveolar type II respiratory epithelial cells by anti-surfactant protein-C antibody-conjugated lipoplexes.
abstract: Alveolar type II (ATII) respiratory epithelial cells are essential to normal lung function. They may be also central to the pathogenesis of diseases such as acute lung injury, pulmonary fibrosis, and pulmonary adenocarcinoma. Hence, ATII cells are important therapeutic targets. However, effective ATII cell-specific drug delivery in vivo requires carriers of an appropriate size, which can cross the hydrophobic alveolar surfactant film and polar aqueous layer overlying ATII cells, and be taken up without inducing ATII cell dysfunction, pulmonary inflammation, lung damage, or excessive systemic spread and side-effects. We have developed lipoplexes as a versatile nanoparticle carrier system for drug/RNA delivery. To optimize their pulmonary localization and ATII cell specificity, lipoplexes were conjugated to an antibody directed against the ATII cell-specific antigen surfactant protein-C (SP-C) then administered to C57BL/6 mice via the nares. Intranasally-administered, anti-SP-C-conjugated lipoplexes targeted mouse ATII cells with >70% specificity in vivo, were retained within ATII cells for at least 48h, and did not accumulate at significant levels in other lung cell types or viscera. 48h after treatment with anti-SP-C-conjugated lipoplexes containing the test microRNA miR-486, expression of mature miR-486 was approximately 4-fold higher in ATII cells than whole lung by qRT-PCR, and was undetectable in other viscera. Lipoplexes induced no weight loss, hypoxemia, lung dysfunction, pulmonary edema, or pulmonary inflammation over a 6-day period. These findings indicate that ATII cell-targeted lipoplexes exhibit all the desired characteristics of an effective drug delivery system for the treatment of pulmonary diseases that result primarily from ATII cell dysfunction.
authors: Dept. of Biomedical Engineering, State University of New York at Buffalo, Bonner Hall, Buffalo, NY 14260, USA; Nanoscale Science and Engineering Center for Affordable Nanoengineering of Polymeric Biomedical Devices, The Ohio State University, Smith Laboratory, 174W. 18th Ave., Columbus, OH 43210, USA. Electronic address: ywu32@buffalo.edu.
authors: Yun
authors: Y
authors: Wu
authors: Nanoscale Science and Engineering Center for Affordable Nanoengineering of Polymeric Biomedical Devices, The Ohio State University, Smith Laboratory, 174W. 18th Ave., Columbus, OH 43210, USA. Electronic address: junyuma@hotmail.com.
authors: Junyu
authors: J
authors: Ma
authors: Dept. of Veterinary Biosciences, The Ohio State University, Goss Laboratories, 1925 Coffey Road, Columbus, OH 43210, USA. Electronic address: Parker.Woods@osumc.edu.
authors: Parker S
authors: PS
authors: Woods
authors: Dept. of Microbial Infection & Immunity, The Ohio State University, Biomedical Research Tower, 460W. 12th Ave., Columbus, OH 43210, USA. Electronic address: chesarino.1@buckeyemail.osu.edu.
authors: Nicholas M
authors: NM
authors: Chesarino
authors: Dept. of Biomedical Engineering, State University of New York at Buffalo, Bonner Hall, Buffalo, NY 14260, USA. Electronic address: cliu36@buffalo.edu.
authors: Chang
authors: C
authors: Liu
authors: Nanoscale Science and Engineering Center for Affordable Nanoengineering of Polymeric Biomedical Devices, The Ohio State University, Smith Laboratory, 174W. 18th Ave., Columbus, OH 43210, USA; William G. Lowrie Dept. of Chemical and Biomolecular Engineering, The Ohio State University, Koffolt Laboratories, 140W. 19th Ave., Columbus, OH 43210, USA. Electronic address: lee.31@osu.edu.
authors: L James
authors: LJ
authors: Lee
authors: Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, The Ohio State University, Davis Heart and Lung Research Institute, 473W. 12th Ave., Columbus, OH 43210, USA. Electronic address: Patrick.Nana-Sinkam@osumc.edu.
authors: Serge P
authors: SP
authors: Nana-Sinkam
authors: Dept. of Veterinary Biosciences, The Ohio State University, Goss Laboratories, 1925 Coffey Road, Columbus, OH 43210, USA. Electronic address: davis.2448@osu.edu.
authors: Ian C
authors: IC
authors: Davis
mesh_terms: D056809:Alveolar Epithelial Cells / Q000276:immunology*; D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D016503:Drug Delivery Systems; D005260:Female; D018014:Gene Transfer Techniques; D006801:Humans; D018796:Immunoconjugates / Q000737:chemistry / Q000276:immunology* / Q000493:pharmacokinetics; D008081:Liposomes / Q000737:chemistry / Q000276:immunology* / Q000493:pharmacokinetics; D008168:Lung / Q000276:immunology; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000008:administration & dosage*; D037721:Pulmonary Surfactant-Associated Protein C / Q000276:immunology*
chemical_list: D018796:Immunoconjugates; D008081:Liposomes; C560945:MIRN486 microRNA, human; D035683:MicroRNAs; D037721:Pulmonary Surfactant-Associated Protein C
keywords: Alveolar type II cell; Lipoplex; MicroRNA; Surfactant protein-C; Targeted delivery