{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T07:53:11Z","timestamp":1772437991217,"version":"3.50.1"},"posted":{"date-parts":[[2026,2,25]]},"group-title":"Bioengineering","reference-count":48,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T00:00:00Z","timestamp":1771977600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"NIAID","doi-asserted-by":"crossref","award":["R01EB024556"],"award-info":[{"award-number":["R01EB024556"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,2,25]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Advanced nanocarrier technologies have reshaped treatment paradigms for inflammatory and degenerative disorders by facilitating cell-specific delivery of bioactive molecules, including nucleic acids. Despite this progress, therapeutic application of microRNAs (miRs) has been hindered by rapid degradation, limited stability in circulation, and suboptimal cytosolic delivery within complex biological environments. In this study, we engineered and validated a macrophage-directed lipid nanoparticle (LNP) system designed to efficiently deliver the anti-inflammatory microRNA miR-146a (MacLNP-miR146a). Mannose-functionalized LNPs were generated through a scalable lipid injection formulation approach, producing highly uniform nanoparticles with strong physicochemical integrity across diverse pH conditions and in serum-rich environments. The optimized four-lipid composition supports efficient miR-146a encapsulation, promotes endosomal escape, and enhances intracellular trafficking, leading to effective cellular uptake and favorable tissue distribution in both\n                  <jats:italic>in vitro<\/jats:italic>\n                  and\n                  <jats:italic>in vivo<\/jats:italic>\n                  models. Notably, MacLNP-miR146a demonstrates strong biocompatibility in primary cell systems and animal studies. Together, these findings position MacLNP-miR146a as a robust and translational nanotherapeutic strategy for modulating macrophage-driven inflammation, including biomaterial-associated foreign body responses and related inflammatory pathologies.\n                <\/jats:p>","DOI":"10.64898\/2026.02.23.707596","type":"posted-content","created":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T18:25:26Z","timestamp":1772043926000},"source":"Crossref","is-referenced-by-count":0,"title":["A novel endosome-escaping, macrophage-targeted nanoparticle platform for miR-146a delivery with favorable in vivo biodistribution and biocompatibility"],"prefix":"10.64898","author":[{"given":"Mohammad I.","family":"Khan","sequence":"first","affiliation":[{"name":"University of Maryland, Department of Nutrition and Food Science, College Park, MD 20742"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karunakaran R.","family":"Sankaran","sequence":"additional","affiliation":[{"name":"University of Maryland, Department of Nutrition and Food Science, College Park, MD 20742"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shaik O.","family":"Rahaman","sequence":"additional","affiliation":[{"name":"University of Maryland, Department of Nutrition and Food Science, College Park, MD 20742"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"issue":"6","key":"2026030122551478000_2026.02.23.707596v1.1","doi-asserted-by":"crossref","first-page":"5421","DOI":"10.1021\/acsnano.2c10042","article-title":"Cysteine-based redox-responsive nanoparticles for fibroblast-targeted drug delivery in the treatment of myocardial infarction","volume":"17","year":"2023","journal-title":"ACS nano"},{"key":"2026030122551478000_2026.02.23.707596v1.2","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.ejpb.2020.12.016","article-title":"Docosahexaenoic acid nanoencapsulated with anti-PECAM-1 as co-therapy for atherosclerosis regression","volume":"159","year":"2021","journal-title":"Eur. 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