{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T14:02:41Z","timestamp":1790431361643,"version":"4.1.0"},"reference-count":37,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2021,7,20]],"date-time":"2021-07-20T00:00:00Z","timestamp":1626739200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"EuroNanoMedIII","award":["ARROWNANO"],"award-info":[{"award-number":["ARROWNANO"]}]},{"DOI":"10.13039\/501100002803","name":"Fondazione Cariplo","doi-asserted-by":"publisher","award":["2017-1892"],"award-info":[{"award-number":["2017-1892"]}],"id":[{"id":"10.13039\/501100002803","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","award":["Ricerca corrente San Matteo"],"award-info":[{"award-number":["Ricerca corrente San Matteo"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Chronic lung allograft dysfunction (CLAD) and interstitial lung disease associated with collagen tissue diseases (CTD-ILD) are two end-stage lung disorders in which different chronic triggers induce activation of myo-\/fibroblasts (LFs). Everolimus, an mTOR inhibitor, can be adopted as a potential strategy for CLAD and CTD-ILD, however it exerts important side effects. This study aims to exploit nanomedicine to reduce everolimus side effects encapsulating it inside liposomes targeted against LFs, expressing a high rate of CD44. PEGylated liposomes were modified with high molecular weight hyaluronic acid and loaded with everolimus (PEG-LIP(ev)-HA400kDa). Liposomes were tested by in vitro experiments using LFs derived from broncholveolar lavage (BAL) of patients affected by CLAD and CTD-ILD, and on alveolar macrophages (AM) and lymphocytes isolated, respectively, from BAL and peripheral blood. PEG-LIP-HA400kDa demonstrated to be specific for LFs, but not for CD44-negative cells, and after loading everolimus, PEG-LIP(ev)-HA400kDa were able to arrest cell cycle arrest and to decrease phospho-mTOR level. PEG-LIP(ev)-HA400kDa showed anti-inflammatory effect on immune cells. This study opens the possibility to use everolimus in lung fibrotic diseases, demonstrating that our lipids-based vehicles can vehicle everolimus inside cells exerting the same drug molecular effect, not only in LFs, but also in immune cells.<\/jats:p>","DOI":"10.3390\/ijms22147743","type":"journal-article","created":{"date-parts":[[2021,7,20]],"date-time":"2021-07-20T11:26:10Z","timestamp":1626780370000},"page":"7743","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Liposomes Loaded with Everolimus and Coated with Hyaluronic Acid: A Promising Approach for Lung Fibrosis"],"prefix":"10.3390","volume":"22","author":[{"given":"Laura","family":"Pandolfi","sequence":"first","affiliation":[{"name":"Research Laboratory of Lung Diseases, Section of Cell Biology, IRCCS Policlinico San Matteo Foundation, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Marengo","sequence":"additional","affiliation":[{"name":"Institut Galien Paris-Saclay, CNRS, Universit\u00e9 Paris-Saclay, Ch\u00e2tenay-Malabry, 92296 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kamila Bohne","family":"Japiassu","sequence":"additional","affiliation":[{"name":"Institut Galien Paris-Saclay, CNRS, Universit\u00e9 Paris-Saclay, Ch\u00e2tenay-Malabry, 92296 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3194-8027","authenticated-orcid":false,"given":"Vanessa","family":"Frangipane","sequence":"additional","affiliation":[{"name":"Research Laboratory of Lung Diseases, Section of Cell Biology, IRCCS Policlinico San Matteo Foundation, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2095-2626","authenticated-orcid":false,"given":"Nicolas","family":"Tsapis","sequence":"additional","affiliation":[{"name":"Institut Galien Paris-Saclay, CNRS, Universit\u00e9 Paris-Saclay, Ch\u00e2tenay-Malabry, 92296 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valeria","family":"Bincoletto","sequence":"additional","affiliation":[{"name":"Department of Drug Science and Technology, University of Turin, 10125 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2557-8514","authenticated-orcid":false,"given":"Veronica","family":"Codullo","sequence":"additional","affiliation":[{"name":"Unit of Rheumatology, IRCCS Policlinico San Matteo Foundation, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Bozzini","sequence":"additional","affiliation":[{"name":"Research Laboratory of Lung Diseases, Section of Cell Biology, IRCCS Policlinico San Matteo Foundation, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Morosini","sequence":"additional","affiliation":[{"name":"Research Laboratory of Lung Diseases, Section of Cell Biology, IRCCS Policlinico San Matteo Foundation, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Lettieri","sequence":"additional","affiliation":[{"name":"Pneumology Unit, IRCCS Policlinico San Matteo Foundation, University of Pavia, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Vertui","sequence":"additional","affiliation":[{"name":"Pneumology Unit, IRCCS Policlinico San Matteo Foundation, University of Pavia, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7275-4229","authenticated-orcid":false,"given":"Davide","family":"Piloni","sequence":"additional","affiliation":[{"name":"Pneumology Unit, IRCCS Policlinico San Matteo Foundation, University of Pavia, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Arpicco","sequence":"additional","affiliation":[{"name":"Department of Drug Science and Technology, University of Turin, 10125 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3194-961X","authenticated-orcid":false,"given":"Elias","family":"Fattal","sequence":"additional","affiliation":[{"name":"Institut Galien Paris-Saclay, CNRS, Universit\u00e9 Paris-Saclay, Ch\u00e2tenay-Malabry, 92296 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"Meloni","sequence":"additional","affiliation":[{"name":"Research Laboratory of Lung Diseases, Section of Cell Biology, IRCCS Policlinico San Matteo Foundation, 27100 Pavia, Italy"},{"name":"Pneumology Unit, IRCCS Policlinico San Matteo Foundation, University of Pavia, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,7,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"S1732","DOI":"10.21037\/jtd.2019.03.83","article-title":"Detection, classification, and management of rejection after lung transplantation","volume":"11","author":"Parulekar","year":"2019","journal-title":"J. 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