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It is crucial to improve the targeting of drugs on tumor cells and tissues. Celastrol (CeT), as an active ingredient of traditional Chinese medicine, possesses strong antitumor effects, especially in triggering apoptosis of HCC. However, due to its toxicity and lack of targeting, its application is greatly limited. HMCLPs, a nano-biomimetic platform carrying CeT with controllable drug release, enhanced targeting, and immunocompatibility, were developed for the first time, which can be used for the treatment of HCC. By utilizing homologous cell membranes and hyaluronic acid (HA), HMCLPs can precisely target tumor regions and release CeT in a controlled manner. Both in vitro and in vivo studies have demonstrated that HMCLPs loaded with CeT significantly increased the accumulation of reactive oxygen species (ROS), induced mitochondrial damage, and triggered apoptosis of HCC cells, resulting in effective treatment with minimal adverse reaction. The development of HMCLPs as a nanocarrier system for CeT delivery offers a promising therapeutic strategy for HCC. This innovative approach improves the targeted delivery and bioavailability of CeT, dramatically induces apoptosis in HCC cells, and exerts its powerful antitumor effects while minimizing systemic toxicity. The present study highlights the potential of combining innovative nanocarriers with powerful natural compounds such as CeT to enhance efficacy and reduce toxicity.<\/jats:p>","DOI":"10.3390\/cells13211819","type":"journal-article","created":{"date-parts":[[2024,11,4]],"date-time":"2024-11-04T09:52:54Z","timestamp":1730713974000},"page":"1819","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Celastrol-Loaded Hyaluronic Acid\/Cancer Cell Membrane Lipid Nanoparticles for Targeted Hepatocellular Carcinoma Prevention"],"prefix":"10.3390","volume":"13","author":[{"given":"Peng","family":"He","sequence":"first","affiliation":[{"name":"Laboratory of Stem Cell Regulation and Application of Traditional Chinese Medicine, School of Pharmacy, Hunan University of Chinese Medicine, Changsha 410208, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manshu","family":"Zou","sequence":"additional","affiliation":[{"name":"Science and Technology Innovation Center, Hunan University of Chinese Medicine, Changsha 410208, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chanjuan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Laboratory of Stem Cell Regulation and Application of Traditional Chinese Medicine, School of Pharmacy, Hunan University of Chinese Medicine, Changsha 410208, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaning","family":"Shi","sequence":"additional","affiliation":[{"name":"Laboratory of Stem Cell Regulation and Application of Traditional Chinese Medicine, School of Pharmacy, Hunan University of Chinese Medicine, Changsha 410208, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9797-2636","authenticated-orcid":false,"given":"Li","family":"Qin","sequence":"additional","affiliation":[{"name":"Laboratory of Stem Cell Regulation and Application of Traditional Chinese Medicine, School of Pharmacy, Hunan University of Chinese Medicine, Changsha 410208, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1053\/j.gastro.2016.11.048","article-title":"Liver Cancer Cell of Origin, Molecular Class, and Effects on Patient Prognosis","volume":"152","author":"Sia","year":"2017","journal-title":"Gastroenterology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/j.canlet.2015.07.018","article-title":"Heterogeneity of liver cancer and personalized therapy","volume":"379","author":"Li","year":"2016","journal-title":"Cancer Lett."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1038\/s41568-021-00383-9","article-title":"The immunological and metabolic landscape in primary and metastatic liver cancer","volume":"21","author":"Li","year":"2021","journal-title":"Nat. Rev. Cancer"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1472","DOI":"10.1038\/s41401-020-00572-6","article-title":"Celastrol induces lipophagy via the LXR\u03b1\/ABCA1 pathway in clear cell renal cell carcinoma","volume":"42","author":"Zhang","year":"2021","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1038\/s41392-022-01231-4","article-title":"Celastrol suppresses colorectal cancer via covalent targeting peroxiredoxin 1","volume":"8","author":"Xu","year":"2023","journal-title":"Signal Transduct. Target Ther."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1016\/j.canlet.2021.08.030","article-title":"Celastrol in cancer therapy: Recent developments, challenges and prospects","volume":"521","author":"Lim","year":"2021","journal-title":"Cancer Lett."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1186\/s13045-021-01096-0","article-title":"Nanomaterials for cancer therapy: Current progress and perspectives","volume":"14","author":"Cheng","year":"2021","journal-title":"J. Hematol. Oncol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"216397","DOI":"10.1016\/j.canlet.2023.216397","article-title":"Nano-drug delivery system targeting tumor microenvironment: A prospective strategy for melanoma treatment","volume":"574","author":"Xu","year":"2023","journal-title":"Cancer Lett."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1016\/j.jconrel.2023.06.038","article-title":"Purification processes of polymeric nanoparticles: How to improve their clinical translation?","volume":"360","author":"Tehrani","year":"2023","journal-title":"J. Control Release"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1016\/j.jconrel.2022.05.054","article-title":"Polymer nanotherapeutics: A versatile platform for effective rheumatoid arthritis therapy","volume":"348","author":"Nooreen","year":"2022","journal-title":"J. Control Release"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1016\/j.jconrel.2024.03.008","article-title":"Liposome-integrated hydrogel hybrids: Promising platforms for cancer therapy and tissue regeneration","volume":"368","author":"Sanati","year":"2024","journal-title":"J. Control Release"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.actbio.2022.12.013","article-title":"Liposome-based diagnostic and therapeutic applications for pancreatic cancer","volume":"157","author":"Raza","year":"2023","journal-title":"Acta Biomater."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Liu, Q., Li, D., Pan, X., and Liang, Y. (2023). Targeted therapy using engineered extracellular vesicles: Principles and strategies for membrane modification. J. Nanobiotechnol., 21.","DOI":"10.1186\/s12951-023-02081-0"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e1803549","DOI":"10.1002\/adma.201803549","article-title":"Hyaluronic Acid-Based Activatable Nanomaterials for Stimuli-Responsive Imaging and Therapeutics: Beyond CD44-Mediated Drug Delivery","volume":"31","author":"Choi","year":"2019","journal-title":"Adv. Mater."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1186\/s12964-023-01143-y","article-title":"Adiponectin affects the migration ability of bone marrow-derived mesenchymal stem cells via the regulation of hypoxia inducible factor 1\u03b1","volume":"21","author":"Soh","year":"2023","journal-title":"Cell Commun. Signal"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1021\/acsnano.1c07556","article-title":"Biomimetic Hybrid Membrane-Coated Xuetongsu Assisted with Laser Irradiation for Efficient Rheumatoid Arthritis Therapy","volume":"16","author":"Yu","year":"2022","journal-title":"ACS Nano"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"5599","DOI":"10.1039\/D1BM00446H","article-title":"An exosome-mimicking membrane hybrid nanoplatform for targeted treatment toward Kras-mutant pancreatic carcinoma","volume":"9","author":"Deng","year":"2021","journal-title":"Biomater. Sci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.actbio.2020.05.028","article-title":"Hybrid cell membrane-coated nanoparticles: A multifunctional biomimetic platform for cancer diagnosis and therapy","volume":"112","author":"Chen","year":"2020","journal-title":"Acta Biomater."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e292","DOI":"10.1002\/ctm2.292","article-title":"Membrane engineering of cell membrane biomimetic nanoparticles for nanoscale therapeutics","volume":"11","author":"Zhang","year":"2021","journal-title":"Clin. Transl. Med."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Yang, N., Li, M., Wu, L., Song, Y., Yu, S., Wan, Y., Cheng, W., Yang, B., Mou, X., and Yu, H. (2023). Peptide-anchored neutrophil membrane-coated biomimetic nanodrug for targeted treatment of rheumatoid arthritis. J. Nanobiotechnol., 21.","DOI":"10.1186\/s12951-023-01773-x"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1016\/j.apsb.2019.01.011","article-title":"Red blood cell membrane-camouflaged nanoparticles: A novel drug delivery system for antitumor application","volume":"9","author":"Xia","year":"2019","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e2100876","DOI":"10.1002\/advs.202100876","article-title":"Multi-Functional Liposome: A Powerful Theranostic Nano-Platform Enhancing Photodynamic Therapy","volume":"8","author":"Cheng","year":"2021","journal-title":"Adv. Sci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1397","DOI":"10.1021\/acs.molpharmaceut.8b01342","article-title":"Inflammation-Targeted Delivery of Celastrol via Neutrophil Membrane-Coated Nanoparticles in the Management of Acute Pancreatitis","volume":"16","author":"Zhou","year":"2019","journal-title":"Mol. Pharm."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1016\/j.jconrel.2023.04.040","article-title":"Unleashing the potential of cell biomimetic nanoparticles: Strategies and challenges in their design and fabrication for therapeutic applications","volume":"358","author":"Zinger","year":"2023","journal-title":"J. Control Release"},{"key":"ref_25","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_26","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1016\/j.apsb.2020.12.018","article-title":"Biological drug and drug delivery-mediated immunotherapy","volume":"11","author":"Xiao","year":"2021","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"888","DOI":"10.1016\/j.jconrel.2023.07.034","article-title":"Extracellular matrix component-derived nanoparticles for drug delivery and tissue engineering","volume":"360","author":"Hogan","year":"2023","journal-title":"J. Control Release"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"117103","DOI":"10.1016\/j.carbpol.2020.117103","article-title":"Drug delivery systems based on CD44-targeted glycosaminoglycans for cancer therapy","volume":"251","author":"Li","year":"2021","journal-title":"Carbohydr. Polym."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e1604","DOI":"10.1038\/cddis.2014.543","article-title":"Celastrol induces apoptosis and autophagy via the ROS\/JNK signaling pathway in human osteosarcoma cells: An in vitro and in vivo study","volume":"6","author":"Li","year":"2015","journal-title":"Cell Death Dis."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"10290","DOI":"10.7150\/thno.46728","article-title":"Celastrol induces ROS-mediated apoptosis via directly targeting peroxiredoxin-2 in gastric cancer cells","volume":"10","author":"Chen","year":"2020","journal-title":"Theranostics"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1186\/s13046-019-1173-4","article-title":"Celastrol mediates autophagy and apoptosis via the ROS\/JNK and Akt\/mTOR signaling pathways in glioma cells","volume":"38","author":"Liu","year":"2019","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"121709","DOI":"10.1016\/j.ijpharm.2022.121709","article-title":"Brain-targeting biomimetic nanoparticles for codelivery of celastrol and LY2157299 for reversing glioma immunosuppression","volume":"619","author":"Zhu","year":"2022","journal-title":"Int. J. Pharm."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Zhou, R., You, Y., Zha, Z., Chen, J., Li, Y., Chen, X., Chen, X., Jiang, X., Chen, J., and Kwan, H.Y. (2023). Biotin decorated celastrol-loaded ZIF-8 nano-drug delivery system targeted epithelial ovarian cancer therapy. Biomed. Pharmacother., 167.","DOI":"10.1016\/j.biopha.2023.115573"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"23746","DOI":"10.1021\/acsnano.3c07555","article-title":"Biomimetic Macrophage Membrane-Camouflaged Nanoparticles Induce Ferroptosis by Promoting Mitochondrial Damage in Glioblastoma","volume":"17","author":"Cao","year":"2023","journal-title":"ACS Nano"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.jconrel.2022.09.002","article-title":"Stealth nanoparticles in oncology: Facing the PEG dilemma","volume":"351","author":"Zalba","year":"2022","journal-title":"J. Control Release"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"4366","DOI":"10.1038\/s41467-024-48838-5","article-title":"Rediscovery of mononuclear phagocyte system blockade for nanoparticle drug delivery","volume":"15","author":"Zelepukin","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_37","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-Sources, Design, Production Methods, and Applications. Pharmaceutics, 14.","DOI":"10.3390\/pharmaceutics14102008"}],"updated-by":[{"DOI":"10.3390\/cells15050426","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2024,11,4]],"date-time":"2024-11-04T00:00:00Z","timestamp":1730678400000}}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/13\/21\/1819\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T10:40:19Z","timestamp":1772448019000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/13\/21\/1819"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,4]]},"references-count":37,"journal-issue":{"issue":"21","published-online":{"date-parts":[[2024,11]]}},"alternative-id":["cells13211819"],"URL":"https:\/\/doi.org\/10.3390\/cells13211819","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,4]]}}}