{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T22:57:22Z","timestamp":1793228242452,"version":"4.5.0"},"reference-count":41,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2024,11,9]],"date-time":"2024-11-09T00:00:00Z","timestamp":1731110400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000738","name":"Department of Veterans Affairs","doi-asserted-by":"publisher","award":["BX002526"],"award-info":[{"award-number":["BX002526"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000738","name":"Department of Veterans Affairs","doi-asserted-by":"publisher","award":["BX004476"],"award-info":[{"award-number":["BX004476"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000738","name":"Department of Veterans Affairs","doi-asserted-by":"publisher","award":["#709144"],"award-info":[{"award-number":["#709144"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000738","name":"Department of Veterans Affairs","doi-asserted-by":"publisher","award":["#833679"],"award-info":[{"award-number":["#833679"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Crohn\u2019s and Colitis Foundation of North America","award":["BX002526"],"award-info":[{"award-number":["BX002526"]}]},{"name":"Crohn\u2019s and Colitis Foundation of North America","award":["BX004476"],"award-info":[{"award-number":["BX004476"]}]},{"name":"Crohn\u2019s and Colitis Foundation of North America","award":["#709144"],"award-info":[{"award-number":["#709144"]}]},{"name":"Crohn\u2019s and Colitis Foundation of North America","award":["#833679"],"award-info":[{"award-number":["#833679"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nanomaterials"],"abstract":"<jats:p>A novel lipid nanoparticle (nLNP), formulated with three essential lipids to mimic ginger-derived exosomal particles, shows strong potential for delivering IL-22 mRNA specifically to the colon, presenting a unique oral drug delivery system for inflammatory bowel disease (IBD). However, its cellular targets and uptake behavior in healthy versus diseased colons remain unclear. Understanding these aspects is crucial for fully elucidating its targeting effectiveness in inflamed colon tissue. This study investigates the nLNP\u2019s cellular targets in healthy and diseased mouse colons. Flow cytometry compared nLNP uptake in healthy mice and a DSS-induced acute colitis model. The results revealed efficient internalization of nLNP by colonic epithelial cells in healthy and inflamed mice. In non-inflamed mice, the small number of colonic macrophages resulted in minimal uptake of nLNP by these cells. In inflamed mice, macrophages migrated to the damaged epithelium, where nLNP uptake was significantly increased, highlighting the nLNP\u2019s ability to target both epithelial and macrophage cells during inflammation. Additionally, safety assessments showed that the nLNP neither altered in vitro kinase activities nor exhibited immunotoxicity or induced in vivo toxicity at the maximum tolerated oral dose. These findings underscore the nLNP\u2019s safety and potential as a promising epithelial\/macrophage-targeted drug delivery platform for oral ulcerative colitis (UC) treatment.<\/jats:p>","DOI":"10.3390\/nano14221800","type":"journal-article","created":{"date-parts":[[2024,11,11]],"date-time":"2024-11-11T03:52:07Z","timestamp":1731297127000},"page":"1800","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Harnessing a Safe Novel Lipid Nanoparticle: Targeted Oral Delivery to Colonic Epithelial and Macrophage Cells in a Colitis Mouse Model"],"prefix":"10.3390","volume":"14","author":[{"given":"Rabeya Jafrin","family":"Mow","sequence":"first","affiliation":[{"name":"Digestive Disease Research Group, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2310-3590","authenticated-orcid":false,"given":"Michal Pawel","family":"Kuczma","sequence":"additional","affiliation":[{"name":"Digestive Disease Research Group, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaodi","family":"Shi","sequence":"additional","affiliation":[{"name":"Digestive Disease Research Group, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4132-6157","authenticated-orcid":false,"given":"Sridhar","family":"Mani","sequence":"additional","affiliation":[{"name":"Albert Einstein College of Medicine, Bronx, NY 10461, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Didier","family":"Merlin","sequence":"additional","affiliation":[{"name":"Digestive Disease Research Group, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303, USA"},{"name":"Atlanta Veterans Affairs Medical Center, Decatur, GA 30302, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0805-1008","authenticated-orcid":false,"given":"Chunhua","family":"Yang","sequence":"additional","affiliation":[{"name":"Digestive Disease Research Group, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303, USA"},{"name":"Atlanta Veterans Affairs Medical Center, Decatur, GA 30302, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"7247238","DOI":"10.1155\/2019\/7247238","article-title":"A Comprehensive Review and Update on the Pathogenesis of Inflammatory Bowel Disease","volume":"2019","author":"Guan","year":"2019","journal-title":"J. Immunol. Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"113","DOI":"10.2147\/JIR.S65979","article-title":"Inflammatory bowel disease: Clinical aspects and treatments","volume":"7","author":"Fakhoury","year":"2014","journal-title":"J. Inflamm. Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e065186","DOI":"10.1136\/bmjopen-2022-065186","article-title":"Global, regional and national burden of inflammatory bowel disease in 204 countries and territories from 1990 to 2019: A systematic analysis based on the Global Burden of Disease Study 2019","volume":"13","author":"Wang","year":"2023","journal-title":"BMJ Open"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1038\/nrgastro.2015.150","article-title":"The global burden of IBD: From 2015 to 2025","volume":"12","author":"Kaplan","year":"2015","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1133","DOI":"10.1093\/ibd\/izy085","article-title":"Determinants of IBD Heritability: Genes, Bugs, and More","volume":"24","author":"Turpin","year":"2018","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"17562848221138160","DOI":"10.1177\/17562848221138160","article-title":"A review of the therapeutic management of ulcerative colitis","volume":"15","author":"Aslam","year":"2022","journal-title":"Therap. Adv. Gastroenterol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"368504241253709","DOI":"10.1177\/00368504241253709","article-title":"Research advancements and perspectives of inflammatory bowel disease: A comprehensive review","volume":"107","author":"Bai","year":"2024","journal-title":"Sci. Prog."},{"key":"ref_8","first-page":"e41120","article-title":"Advancements in Inflammatory Bowel Disease: A Narrative Review of Diagnostics, Management, Epidemiology, Prevalence, Patient Outcomes, Quality of Life, and Clinical Presentation","volume":"15","author":"Muzammil","year":"2023","journal-title":"Cureus"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"456895","DOI":"10.1155\/2015\/456895","article-title":"Five-aminosalicylic Acid: An update for the reappraisal of an old drug","volume":"2015","author":"Perrotta","year":"2015","journal-title":"Gastroenterol. Res. Pract."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1217","DOI":"10.1111\/j.1365-2036.2005.02462.x","article-title":"Experience of 5-aminosalicylate nephrotoxicity in the United Kingdom","volume":"21","author":"Muller","year":"2005","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"11","DOI":"10.5217\/ir.2020.00155","article-title":"Use of thiopurines in inflammatory bowel disease: An update","volume":"20","author":"Singh","year":"2022","journal-title":"Intest. Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1518","DOI":"10.1111\/j.1572-0241.2007.01187.x","article-title":"Thiopurine-induced liver injury in patients with inflammatory bowel disease: A systematic review","volume":"102","author":"Gisbert","year":"2007","journal-title":"Am. J. Gastroenterol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"115","DOI":"10.3949\/ccjm.81a.12121","article-title":"Managing risks of TNF inhibitors: An update for the internist","volume":"81","author":"Hadam","year":"2014","journal-title":"Clevel. Clin. J. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1016\/j.jmii.2013.03.005","article-title":"Risk of tuberculosis infection in anti-TNF-\u03b1 biological therapy: From bench to bedside","volume":"47","author":"Xie","year":"2014","journal-title":"J. Microbiol. Immunol. Infect."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2653","DOI":"10.1182\/blood.V126.23.2653.2653","article-title":"Risk of Non-Hodgkin Lymphoma Following Treatment of Inflammatory Conditions with Tumor Necrosis Factor-Alpha Inhibitors","volume":"126","author":"Calip","year":"2015","journal-title":"Blood"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1016\/j.jconrel.2020.04.032","article-title":"Natural-lipid nanoparticle-based therapeutic approach to deliver 6-shogaol and its metabolites M2 and M13 to the colon to treat ulcerative colitis","volume":"323","author":"Yang","year":"2020","journal-title":"J. Control. Release"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Zhang, Y., Wang, L., Wang, Z.-D., Zhou, Q., Zhou, X., Zhou, T., Guan, Y.-X., and Liu, X. (2023). Surface-anchored microbial enzyme-responsive solid lipid nanoparticles enabling colonic budesonide release for ulcerative colitis treatment. J. Nanobiotechnol., 21.","DOI":"10.1186\/s12951-023-01889-0"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1038\/s41573-020-0090-8","article-title":"Engineering precision nanoparticles for drug delivery","volume":"20","author":"Mitchell","year":"2021","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Ashfaq, R., Rasul, A., Asghar, S., Kov\u00e1cs, A., Berk\u00f3, S., and Budai-Sz\u0171cs, M. (2023). Lipid Nanoparticles: An Effective Tool to Improve the Bioavailability of Nutraceuticals. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms242115764"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/17425247.2020.1698543","article-title":"Can naturally occurring nanoparticle-based targeted drug delivery effectively treat inflammatory bowel disease?","volume":"17","author":"Yang","year":"2020","journal-title":"Expert. Opin. Drug Deliv."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Yu, L., Deng, Z., Liu, L., Zhang, W., and Wang, C. (2020). Plant-Derived Nanovesicles: A Novel Form of Nanomedicine. Front. Bioeng. Biotechnol., 8.","DOI":"10.3389\/fbioe.2020.584391"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1186\/s12934-023-02243-7","article-title":"Prausnitzii-derived extracellular vesicles attenuate experimental colitis by regulating intestinal homeostasis in mice","volume":"22","author":"Ye","year":"2023","journal-title":"Microb. Cell Fact."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Balboni, A., Ailuno, G., Baldassari, S., Drava, G., Petretto, A., Grinovero, N., Cavalleri, O., Angeli, E., Lagomarsino, A., and Canepa, P. (2024). Human glioblastoma-derived cell membrane nanovesicles: A novel, cell-specific strategy for boron neutron capture therapy of brain tumors. Sci. Rep., 14.","DOI":"10.1038\/s41598-024-69696-7"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Mougenot, M.F., Pereira, V.S., Costa, A.L.R., Lancellotti, M., Porcionatto, M.A., da Silveira, J.C., and de la Torre, L.G. (2022). Biomimetic Nanovesicles\u2014Sources, Design, Production Methods, and Applications. Pharmaceutics, 14.","DOI":"10.3390\/pharmaceutics14102008"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Sung, J., Alghoul, Z., Long, D., Yang, C., and Merlin, D. (2022). Oral delivery of IL-22 mRNA-loaded lipid nanoparticles targeting the injured intestinal mucosa: A novel therapeutic solution to treat ulcerative colitis. Biomaterials, 288.","DOI":"10.1016\/j.biomaterials.2022.121707"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Long, D., Yang, C., Sung, J., and Merlin, D. (2021). Atomic Force Microscopy to Characterize Ginger Lipid-Derived Nanoparticles (GLDNP). Bio-Protocol, 11.","DOI":"10.21769\/BioProtoc.3969"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Mow, R.J., Srinivasan, A., Bolay, E., Merlin, D., and Yang, C. (2024). Fluorescent Labeling and Imaging of IL-22 mRNA-Loaded Lipid Nanoparticles. Bio-Protocol, 14.","DOI":"10.21769\/BioProtoc.4994"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Morral, C., Ghinnagow, R., Karakasheva, T., Zhou, Y., Thadi, A., Li, N., Yoshor, B., Soto, G., Chen, C., and Aleynick, D. (2023). Isolation of Epithelial and Stromal Cells from Colon Tissues in Homeostasis and Under Inflammatory Conditions. Bio-Protocol, 13.","DOI":"10.21769\/BioProtoc.4825"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"eaaz3186","DOI":"10.1126\/sciadv.aaz3186","article-title":"Commensal epitopes drive differentiation of colonic T(regs)","volume":"6","author":"Kuczma","year":"2020","journal-title":"Sci. Adv."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1016\/j.biomaterials.2016.06.018","article-title":"Edible ginger-derived nanoparticles: A novel therapeutic approach for the prevention and treatment of inflammatory bowel disease and colitis-associated cancer","volume":"101","author":"Zhang","year":"2016","journal-title":"Biomaterials"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1196","DOI":"10.1093\/ibd\/izz011","article-title":"Acute Colitis Drives Tolerance by Persistently Altering the Epithelial Barrier and Innate and Adaptive Immunity","volume":"25","author":"Wardill","year":"2019","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"101333","DOI":"10.1016\/j.jcmgh.2024.03.005","article-title":"Unleashing the Potential of Oral Deliverable Nanomedicine in the Treatment of Inflammatory Bowel Disease","volume":"18","author":"Yang","year":"2024","journal-title":"Cell. Mol. Gastroenterol. Hepatol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1501","DOI":"10.2217\/nnm-2022-0222","article-title":"Lipid nanoparticles for oral delivery of nucleic acids for treating inflammatory bowel disease","volume":"17","author":"Yang","year":"2022","journal-title":"Nanomedicine"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1867","DOI":"10.1038\/ncomms2886","article-title":"Delivery of Therapeutic Agents by Nanoparticles Made of Grapefruit-Derived Lipids","volume":"4","author":"Wang","year":"2013","journal-title":"Nat. Commun."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"137963","DOI":"10.1016\/j.foodchem.2023.137963","article-title":"Plant exosome-like nanovesicles derived from sesame leaves as carriers for luteolin delivery: Molecular docking, stability, and bioactivity","volume":"438","author":"Jiang","year":"2024","journal-title":"Food Chem."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Zu, M., Xie, D., Canup, B.S., Chen, N., Wang, Y., Sun, R., Zhang, Z., Fu, Y., Dai, F., and Xiao, B. (2021). \u2018Green\u2019 nanotherapeutics from tea leaves for orally targeted prevention and alleviation of colon diseases. Biomaterials, 279.","DOI":"10.1016\/j.biomaterials.2021.121178"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1016\/j.apsb.2021.08.016","article-title":"Natural exosome-like nanovesicles from edible tea flowers suppress metastatic breast cancer via ROS generation and microbiota modulation","volume":"12","author":"Chen","year":"2022","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"5596","DOI":"10.7150\/thno.73650","article-title":"Turmeric-derived nanovesicles as novel nanobiologics for targeted therapy of ulcerative colitis","volume":"12","author":"Gao","year":"2022","journal-title":"Theranostics"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Hu, G., Guo, M., Xu, J., Wu, F., Fan, J., Huang, Q., Yang, G., Lv, Z., Wang, X., and Jin, Y. (2019). Nanoparticles Targeting Macrophages as Potential Clinical Therapeutic Agents Against Cancer and Inflammation. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.01998"},{"key":"ref_40","unstructured":"Bonner, J.C., and Brown, J.M. (2020). Macrophages: First Innate Immune Responders to Nanomaterials. Interaction of Nanomaterials with the Immune System, Springer International Publishing."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"106609","DOI":"10.1016\/j.vascn.2019.106609","article-title":"Safety screening in early drug discovery: An optimized assay panel","volume":"99","author":"Bendels","year":"2019","journal-title":"J. Pharmacol. Toxicol. Methods"}],"container-title":["Nanomaterials"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-4991\/14\/22\/1800\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:29:23Z","timestamp":1760113763000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-4991\/14\/22\/1800"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,9]]},"references-count":41,"journal-issue":{"issue":"22","published-online":{"date-parts":[[2024,11]]}},"alternative-id":["nano14221800"],"URL":"https:\/\/doi.org\/10.3390\/nano14221800","relation":{},"ISSN":["2079-4991"],"issn-type":[{"value":"2079-4991","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,9]]}}}