{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T15:54:34Z","timestamp":1765209274659,"version":"3.46.0"},"reference-count":57,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T00:00:00Z","timestamp":1765152000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["22174031","22374033"],"award-info":[{"award-number":["22174031","22374033"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005046","name":"Natural Science Foundation of Heilongjiang Province","doi-asserted-by":"publisher","award":["ZD2022B001"],"award-info":[{"award-number":["ZD2022B001"]}],"id":[{"id":"10.13039\/501100005046","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nanomaterials"],"abstract":"<jats:p>Messenger RNA therapy represents a transformative therapeutic in vaccine development, tumor immunotherapy, and genetic disease intervention. Polyethylene glycol (PEG) lipid, a key component of ionizable lipid nanoparticles (iLNPs) for mRNA delivery, and the PEG antibodies induced by PEG are associated with hypersensitivity and accelerated blood clearance. To address the above PEG-associated challenges, we systematically investigated polysorbate 20 (PS20) as an alternative for constructing PEG-free iLNPs. The formulation of PS20-incorporated iLNPs (PS20-iLNPs) for carrying mRNA was systematically investigated by analyzing the particle size, pKa, endosomal escape efficiency, and cellular internalization efficiency of iLNPs with different molar ratio PS20 content (0.5\u20135.0%). iLNPs with a relative molar ratio of 2.5% were identified as the optimal mRNA delivery carrier. This carrier exhibited excellent resistance to serum protein adsorption capacity, with serum stability 1.3-fold higher than PEG-iLNPs. At high lipid concentrations (2.7 mg\/mL), the cell viability of PS20-iLNPs was maintained at 91.1%, which was 1.07-fold higher than PEG-iLNPs. Under serum interference, PS20-iLNPs achieved a transfection efficiency of 46.5%, marking a 10.6% improvement over PEG-iLNPs under identical conditions. Notably, PS20-iLNPs exhibited 24 times higher spleen accumulation than PEG-iLNPs. These findings highlight PS20 as a viable PEG substitute for developing PEG-free spleen-accumulated mRNA delivery platforms with enhanced therapeutic potential.<\/jats:p>","DOI":"10.3390\/nano15241844","type":"journal-article","created":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T14:52:24Z","timestamp":1765205544000},"page":"1844","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Construction of Spleen-Accumulated Polysorbate 20-Containing Ionizable Lipid Nanoparticles for mRNA Delivery"],"prefix":"10.3390","volume":"15","author":[{"given":"Hanyu","family":"Liu","sequence":"first","affiliation":[{"name":"State Key Laboratory of Urban-Rural Water Resource and Environment, MIIT Key Laboratory of Critical Materials Technology for New Energy Conversion and Storage, Heilongjiang Provincial Joint Laboratory of Molecular Science (International Cooperation), School of Chemistry and Chemical Engineering, Harbin Institute of Technology, Harbin 150001, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Siqi","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Urban-Rural Water Resource and Environment, MIIT Key Laboratory of Critical Materials Technology for New Energy Conversion and Storage, Heilongjiang Provincial Joint Laboratory of Molecular Science (International Cooperation), School of Chemistry and Chemical Engineering, Harbin Institute of Technology, Harbin 150001, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kexin","family":"Chen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Urban-Rural Water Resource and Environment, MIIT Key Laboratory of Critical Materials Technology for New Energy Conversion and Storage, Heilongjiang Provincial Joint Laboratory of Molecular Science (International Cooperation), School of Chemistry and Chemical Engineering, Harbin Institute of Technology, Harbin 150001, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuyi","family":"Yao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Urban-Rural Water Resource and Environment, MIIT Key Laboratory of Critical Materials Technology for New Energy Conversion and Storage, Heilongjiang Provincial Joint Laboratory of Molecular Science (International Cooperation), School of Chemistry and Chemical Engineering, Harbin Institute of Technology, Harbin 150001, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuefeng","family":"Tang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Urban-Rural Water Resource and Environment, MIIT Key Laboratory of Critical Materials Technology for New Energy Conversion and Storage, Heilongjiang Provincial Joint Laboratory of Molecular Science (International Cooperation), School of Chemistry and Chemical Engineering, Harbin Institute of Technology, Harbin 150001, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8571-6187","authenticated-orcid":false,"given":"Xiaojun","family":"Han","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Urban-Rural Water Resource and Environment, MIIT Key Laboratory of Critical Materials Technology for New Energy Conversion and Storage, Heilongjiang Provincial Joint Laboratory of Molecular Science (International Cooperation), School of Chemistry and Chemical Engineering, Harbin Institute of Technology, Harbin 150001, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"115175","DOI":"10.1016\/j.addr.2023.115175","article-title":"The immunostimulatory nature of mRNA lipid nanoparticles","volume":"205","author":"Sharma","year":"2024","journal-title":"Adv. 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