{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T15:52:09Z","timestamp":1790697129048,"version":"4.1.0"},"reference-count":72,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2022,6,29]],"date-time":"2022-06-29T00:00:00Z","timestamp":1656460800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010661","name":"European Union\u2019s Horizon 2020 Research and Innovation Programme","doi-asserted-by":"publisher","award":["765912"],"award-info":[{"award-number":["765912"]}],"id":[{"id":"10.13039\/100010661","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Autophagy is a fundamental housekeeping process by which cells degrade their components to maintain homeostasis. Defects in autophagy have been associated with aging, neurodegeneration and metabolic diseases. Non-alcoholic fatty liver diseases (NAFLDs) are characterized by hepatic fat accumulation with or without inflammation. No treatment for NAFLDs is currently available, but autophagy induction has been proposed as a promising therapeutic strategy. Here, we aimed to design autophagy-inducing particles, using the autophagy-inducing peptide (Tat-Beclin), and achieve liver targeting in vivo, taking NAFLD as a model disease. Polylactic acid (PLA) particles were prepared by nanoprecipitation without any surfactant, followed by surface peptide adsorption. The ability of Tat-Beclin nanoparticles (NP T-B) to modulate autophagy and to decrease intracellular lipid was evaluated in vitro by LC3 immunoblot and using a cellular model of steatosis, respectively. The intracellular localization of particles was evaluated by transmission electron microscopy (TEM). Finally, biodistribution of fluorescent NP T-B was evaluated in vivo using tomography in normal and obese mice. The results showed that NP T-B induce autophagy with a long-lasting and enhanced effect compared to the soluble peptide, and at a ten times lower dose. Intracellular lipid also decreased in a cellular model of NAFLD after treatment with T-B and NP T-B under the same dose conditions. Ultrastructural studies revealed that NP T-B are internalized and located in endosomal, endolysosomal and autolysosomal compartments, while in healthy and obese mice, NP T-B could accumulate for several days in the liver. Given the beneficial effects of autophagy-inducing particles in vitro, and their capacity to target the liver of normal and obese mice, NP T-B could be a promising therapeutic tool for NAFLDs, warranting further in vivo investigation.<\/jats:p>","DOI":"10.3390\/pharmaceutics14071379","type":"journal-article","created":{"date-parts":[[2022,6,29]],"date-time":"2022-06-29T22:43:28Z","timestamp":1656542608000},"page":"1379","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Design and Evaluation of Autophagy-Inducing Particles for the Treatment of Abnormal Lipid Accumulation"],"prefix":"10.3390","volume":"14","author":[{"given":"Stavroula","family":"Zagkou","sequence":"first","affiliation":[{"name":"Adjuvatis, 60 Avenue Rockefeller, 69008 Lyon, France"},{"name":"Laboratory of Tissue Biology and Therapeutic Engineering, CNRS UMR 5305, Universit\u00e9 Claude Bernard Lyon 1, CEDEX 7, 69367 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentine","family":"Marais","sequence":"additional","affiliation":[{"name":"Adjuvatis, 60 Avenue Rockefeller, 69008 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Narimane","family":"Zeghoudi","sequence":"additional","affiliation":[{"name":"Adjuvatis, 60 Avenue Rockefeller, 69008 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edouard Le","family":"Guillou","sequence":"additional","affiliation":[{"name":"INSERM UMR-S1151, CNRS UMR-S8253, Institut Necker Enfants Malades, Universit\u00e9 Paris Cit\u00e9, 75015 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0006-7785","authenticated-orcid":false,"given":"Eeva-Liisa","family":"Eskelinen","sequence":"additional","affiliation":[{"name":"Institute of Biomedicine, University of Turku, 20520 Turku, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5591-848X","authenticated-orcid":false,"given":"Ganna","family":"Panasyuk","sequence":"additional","affiliation":[{"name":"INSERM UMR-S1151, CNRS UMR-S8253, Institut Necker Enfants Malades, Universit\u00e9 Paris Cit\u00e9, 75015 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8478-7095","authenticated-orcid":false,"given":"Bernard","family":"Verrier","sequence":"additional","affiliation":[{"name":"Adjuvatis, 60 Avenue Rockefeller, 69008 Lyon, France"},{"name":"Laboratory of Tissue Biology and Therapeutic Engineering, CNRS UMR 5305, Universit\u00e9 Claude Bernard Lyon 1, CEDEX 7, 69367 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte","family":"Primard","sequence":"additional","affiliation":[{"name":"Adjuvatis, 60 Avenue Rockefeller, 69008 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.1038\/nature06639","article-title":"Autophagy fights disease through cellular selfdigestion","volume":"451","author":"Mizushima","year":"2008","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"R29","DOI":"10.1016\/j.cub.2011.11.034","article-title":"Mechanisms of Autophagosome Biogenesis","volume":"22","author":"Rubinsztein","year":"2012","journal-title":"Curr. 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