{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T05:01:45Z","timestamp":1787029305521,"version":"build-2736575974"},"reference-count":26,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T00:00:00Z","timestamp":1761782400000},"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":"crossref","award":["21961017"],"award-info":[{"award-number":["21961017"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Yunnan Agricultural Basic Research Project","award":["202301BD070001-225"],"award-info":[{"award-number":["202301BD070001-225"]}]},{"name":"China Agriculture Research System of MOF and MARA","award":["CARS-16-E07"],"award-info":[{"award-number":["CARS-16-E07"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Background\/Objectives: Lipid nanoparticles (LNPs) have demonstrated notable clinical success as advanced drug delivery systems. However, the development of novel covalently bonded ionizable lipids faces substantial technical challenges, as their modification is difficult and they have a high molecular weight. To address this issue, we report the use of host\u2013guest complexes in supramolecular chemistry as functional lipid motifs for constructing LNPs. Methods: Ionizable amine \u03b2-cyclodextrin (amine \u03b2-CD)-derived host\u2013guest amphiphilic lipid molecules (HGLs) were designed for the construction of multi-stage assembly supramolecular LNPs (MSLNPs). The structure\u2013function relationships and stability of MSLNPs were explored by screening eight types of amine \u03b2-CDs and varying the ratio of HGL to yolk phosphatidylcholine. Stability screening and molecular dynamics simulations were performed to clarify the self-assembly mechanisms and optimal formulations, followed by a systematic evaluation of delivery performance. Results: MSLNPs showed a high drug-loading efficiency (&gt; 30%), a rapid-response release in acidic environments, and multi-pathway cellular uptake. In vivo delivery experiments using ethylenediamine \u03b2-CD-based MSLNPs in mice revealed no significant immunogenicity, no significant abnormalities in organs\/tissues or their functions, a unique biodistribution pattern, and pronounced renal targeting. The successful development of MSLNPs with acidic pH-responsive control, a high delivery efficiency, and renal-targeting properties simplifies LNP preparation. Conclusions: This study offers novel insights into the design of simplified LNPs and the optimization of targeted delivery, with potential applications in renal disease therapy.<\/jats:p>","DOI":"10.3390\/pharmaceutics17111410","type":"journal-article","created":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T01:23:59Z","timestamp":1761873839000},"page":"1410","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Supramolecular Lipid Nanoparticles Based on Amine \u03b2-CD Host\u2013Guest Lipids: Design, Mechanisms, and Biosafety"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9377-2736","authenticated-orcid":false,"given":"Pin","family":"Lv","sequence":"first","affiliation":[{"name":"Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming 650500, China"},{"name":"Industrial Crop Research Institute, Yunnan Academy of Agricultural Sciences, Kunming 650225, China"},{"name":"Yunnan Key Laboratory of Genetic Improvement of Herbal Oil Crops, Kunming 650225, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yamin","family":"Li","sequence":"additional","affiliation":[{"name":"Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming 650500, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gang","family":"Du","sequence":"additional","affiliation":[{"name":"Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming 650500, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiawei","family":"Ding","sequence":"additional","affiliation":[{"name":"Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming 650500, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiawei","family":"Zhou","sequence":"additional","affiliation":[{"name":"Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming 650500, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Industrial Crop Research Institute, Yunnan Academy of Agricultural Sciences, Kunming 650225, China"},{"name":"Yunnan Key Laboratory of Genetic Improvement of Herbal Oil Crops, Kunming 650225, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huang","family":"Lin","sequence":"additional","affiliation":[{"name":"Industrial Crop Research Institute, Yunnan Academy of Agricultural Sciences, Kunming 650225, China"},{"name":"Yunnan Key Laboratory of Genetic Improvement of Herbal Oil Crops, Kunming 650225, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Yang","sequence":"additional","affiliation":[{"name":"Industrial Crop Research Institute, Yunnan Academy of Agricultural Sciences, Kunming 650225, China"},{"name":"Yunnan Key Laboratory of Genetic Improvement of Herbal Oil Crops, Kunming 650225, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Zhou","sequence":"additional","affiliation":[{"name":"Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming 650500, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Yang","sequence":"additional","affiliation":[{"name":"Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming 650500, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e2400633","DOI":"10.1002\/smtd.202400633","article-title":"Lipid nanoparticle-mRNA engineered dendritic cell based adoptive cell therapy enhances cancer immune response","volume":"9","author":"Das","year":"2025","journal-title":"Small Methods"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"13790","DOI":"10.1021\/acsnano.4c16617","article-title":"Lipid nanoparticles for in vivo lung delivery of CRISPR-Cas9 ribonucleoproteins allow gene editing of clinical targets","volume":"19","author":"Haley","year":"2025","journal-title":"ACS Nano"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e2305300","DOI":"10.1002\/adma.202305300","article-title":"Lipid nanoparticles optimized for targeting and release of nucleic acid","volume":"36","author":"Jia","year":"2024","journal-title":"Adv. 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