{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:10:42Z","timestamp":1792789842422,"version":"4.5.0"},"reference-count":39,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,1,20]],"date-time":"2023-01-20T00:00:00Z","timestamp":1674172800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"CAMS Innovation Fund for Medical Science (CIFMS)","award":["2022-I2M-2-002"],"award-info":[{"award-number":["2022-I2M-2-002"]}]},{"name":"CAMS Innovation Fund for Medical Science (CIFMS)","award":["2021-I2M-1-031"],"award-info":[{"award-number":["2021-I2M-1-031"]}]},{"name":"CAMS Innovation Fund for Medical Science (CIFMS)","award":["2021-I2M-1-071"],"award-info":[{"award-number":["2021-I2M-1-071"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>The therapeutic efficacy of nanoscale drug delivery systems is related to particle size, zeta potential, morphology, and other physicochemical properties. The structure and composition of nanocarriers may affect their physicochemical properties. To systematically evaluate these characteristics, three analogues, namely polyethylene glycol (PEG), PEG-conjugated octadecylamine (PEG-C18), and tri(ethylene glycol) (TEG), were explored as nanocarriers to entrap celastrol (CSL) via the injection-combined dialysis method. CSL nanoparticles were successfully prepared as orange milky solutions, which revealed a similar particle size of approximately 120 nm, with narrow distribution and a negative zeta potential of \u221220 mV. All these CSL nanoparticles exhibited good storage stability and media stability but presented different drug-loading capacities (DLCs), release profiles, cytotoxicity, and hemolytic activity. For DLCs, PEG-C18\/CSL exhibited better CSL entrapment capacity. Regarding the release profiles, TEG\/CSL showed the lowest release rate, PEG-C18\/CSL presented a moderate release rate, and PEG\/CSL exhibited a relatively fast release rate. Based on the different release rates, PEG-C18\/CSL and TEG\/CSL showed higher degrees of cytotoxicity than PEG\/CSL. Furthermore, TEG\/CSL showed the lowest membrane toxicity, and its hemolytic rate was below 20%. These results suggest that the structural effects of nanocarriers can affect the interactions between nanocarriers and drugs, resulting in different release profiles and antitumor activity.<\/jats:p>","DOI":"10.3390\/molecules28031040","type":"journal-article","created":{"date-parts":[[2023,1,20]],"date-time":"2023-01-20T02:35:55Z","timestamp":1674182155000},"page":"1040","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["A Celastrol Drug Delivery System Based on PEG Derivatives: The Structural Effects of Nanocarriers"],"prefix":"10.3390","volume":"28","author":[{"given":"Yansong","family":"Zhang","sequence":"first","affiliation":[{"name":"College of Food and Drug, Luoyang Normal University, Luoyang 471934, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lijuan","family":"Ding","sequence":"additional","affiliation":[{"name":"Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, No. 151, Malianwa North Road, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, No. 151, Malianwa North Road, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangtao","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, No. 151, Malianwa North Road, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Yu","sequence":"additional","affiliation":[{"name":"Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, No. 151, Malianwa North Road, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei","family":"Jia","sequence":"additional","affiliation":[{"name":"Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, No. 151, Malianwa North Road, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meihua","family":"Han","sequence":"additional","affiliation":[{"name":"Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, No. 151, Malianwa North Road, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yifei","family":"Guo","sequence":"additional","affiliation":[{"name":"Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, No. 151, Malianwa North Road, Beijing 100193, China"},{"name":"Key Laboratory of New Drug Discovery Based on Classic Chinese Medicine Prescription, Chinese Academy of Medical Sciences, No. 151, Malianwa North Road, Beijing 100193, China"},{"name":"Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1016\/j.jconrel.2020.08.045","article-title":"Nanoscale drug delivery systems for controllable drug behaviors by multi-stage barrier penetration","volume":"331","author":"Wang","year":"2021","journal-title":"J. Control. Release"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.jconrel.2014.04.015","article-title":"Nano-niosomes as nanoscale drug delivery systems: An illustrated review","volume":"185","author":"Moghassemi","year":"2014","journal-title":"J. Control. Release"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"4098","DOI":"10.1016\/j.apsb.2022.08.013","article-title":"Smart drug delivery systems for precise cancer therapy","volume":"12","author":"Wang","year":"2022","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1705436","DOI":"10.1002\/adma.201705436","article-title":"Dimeric Drug Polymeric Micelles with Acid-Active Tumor Targeting and FRET-Traceable Drug Release","volume":"30","author":"Guo","year":"2018","journal-title":"Adv. Mater."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1002\/(SICI)1521-4095(199802)10:3<195::AID-ADMA195>3.0.CO;2-V","article-title":"Amphiphilic Block Copolymers in Structure-Controlled Nanomaterial Hybrids","volume":"10","author":"Antonietti","year":"1998","journal-title":"Adv. Mater."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1517","DOI":"10.1021\/ja1090113","article-title":"Controlling the Self-Assembly Structure of Magnetic Nanoparticles and Amphiphilic Block-Copolymers: From Micelles to Vesicles","volume":"133","author":"Hickey","year":"2011","journal-title":"J. Am. Chem. Soc."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1343","DOI":"10.1002\/jps.10397","article-title":"Amphiphilic block copolymers for drug delivery","volume":"92","author":"Adams","year":"2003","journal-title":"J. Pharm. Sci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.jconrel.2017.06.019","article-title":"Self-assembled amphiphilic core-shell nanocarriers in line with the modern strategies for brain delivery","volume":"261","author":"Elezaby","year":"2017","journal-title":"J. Control. Release"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.colsurfb.2018.08.019","article-title":"Amphiphilic core-shell nanoparticles: Synthesis, biophysical properties, and applications","volume":"172","author":"Panday","year":"2018","journal-title":"Colloids Surf. B-Biointerfaces"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1527","DOI":"10.1021\/la503869d","article-title":"Core-Shell Structure, Biodegradation, and Drug Release Behavior of Poly(lactic acid)\/Poly(ethylene glycol) Block Copolymer Micelles Tuned by Macromolecular Stereostructure","volume":"31","author":"Ma","year":"2015","journal-title":"Langmuir"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1021\/acsbiomaterials.5b00122","article-title":"Biodegradable PEG-Based Amphiphilic Block Copolymers for Tissue Engineering Applications","volume":"1","author":"Kutikov","year":"2015","journal-title":"Acs Biomater. Sci. Eng."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Mendes, L.P., Pan, J., and Torchilin, V.P. (2017). Dendrimers as Nanocarriers for Nucleic Acid and Drug Delivery in Cancer Therapy. Molecules, 22.","DOI":"10.3390\/molecules22091401"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"111752","DOI":"10.1016\/j.colsurfb.2021.111752","article-title":"Co-administration of a branched arginine-rich polymer enhances the anti-cancer efficacy of doxorubicin","volume":"203","author":"Huang","year":"2021","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.ejps.2016.11.029","article-title":"Composition-dependent structural changes and antitumor activity of ASC-DP\/DSPE-PEG nanoparticles","volume":"99","author":"Higashi","year":"2017","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"4243","DOI":"10.1021\/acs.chemmater.6b00877","article-title":"Size-Controlled Functionalized Mesoporous Silica Nanoparticles for Tunable Drug Release and Enhanced Anti-Tumoral Activity","volume":"28","author":"Bouchoucha","year":"2016","journal-title":"Chem. Mater."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"11074","DOI":"10.1039\/D0RA01421D","article-title":"The influence of nanocarrier architectures on antitumor efficacy of docetaxel nanoparticles","volume":"10","author":"Dong","year":"2020","journal-title":"Rsc. Adv."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1039\/C4PY01380H","article-title":"Amphiphilic poly(ethylene glycol)-poly(\u03b5-caprolactone) AB2 miktoarm copolymers for self-assembled nanocarrier systems: Synthesis, characterization, and effects of morphology on antitumor activity","volume":"6","author":"Yoon","year":"2015","journal-title":"Polym. Chem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1903243","DOI":"10.1002\/advs.201903243","article-title":"A Nanostrategy for Efficient Imaging-Guided Antitumor Therapy through a Stimuli-Responsive Branched Polymeric Prodrug","volume":"7","author":"Cai","year":"2020","journal-title":"Adv. Sci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1562","DOI":"10.1021\/mp9001206","article-title":"Synthesis and In Vivo Antitumor Efficacy of PEGylated Poly(L-lysine) Dendrimer-Camptothecin Conjugates","volume":"6","author":"Fox","year":"2009","journal-title":"Mol. Pharm."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.jconrel.2016.09.036","article-title":"Smart nanoparticles with a detachable outer shell for maximized synergistic antitumor efficacy of therapeutics with varying physicochemical properties","volume":"243","author":"Yin","year":"2016","journal-title":"J. Control. Release"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1016\/j.addr.2012.09.022","article-title":"PEGylated nanoparticles for biological and pharmaceutical applications","volume":"64","author":"Otsuka","year":"2012","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1564","DOI":"10.1166\/jbn.2021.3126","article-title":"Honokiol-Based Nanomedicine Decorated with Ethylene Glycols Derivatives Promotes Antitumor Efficacy","volume":"17","author":"Dong","year":"2021","journal-title":"J. Biomed. Nanotechnol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.ejpb.2018.12.003","article-title":"Hydroxycamptothecin nanoparticles based on poly\/oligo (ethylene glycol): Architecture effects of nanocarriers on antitumor efficacy","volume":"134","author":"Guo","year":"2019","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1016\/j.ejps.2018.08.043","article-title":"Effect of alkyl chain on cellular uptake and antitumor activity of hydroxycamptothecin nanoparticles based on amphiphilic linear molecules","volume":"124","author":"Guo","year":"2018","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1205","DOI":"10.1021\/acs.molpharmaceut.9b01228","article-title":"Influence of Hydrophobic Chains in Nanocarriers on Antitumor Efficacy of Docetaxel Nanoparticles","volume":"17","author":"Dong","year":"2020","journal-title":"Mol. Pharm."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"85547","DOI":"10.1039\/C5RA12177A","article-title":"A series of codendrimers from polyamidoamine (PAMAM) and oligoethylene glycols (OEG) dendrons as drug carriers: The effect of OEG dendron decoration degree","volume":"5","author":"Zhao","year":"2015","journal-title":"Rsc. Adv."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1016\/j.addr.2009.03.009","article-title":"Nanoparticle interaction with plasma proteins as it relates to particle biodistribution, biocompatibility and therapeutic efficacy","volume":"61","author":"Aggarwal","year":"2009","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1021\/mp800032f","article-title":"Preclinical studies to understand nanoparticle interaction with the immune system and its potential effects on nanoparticle biodistribution","volume":"5","author":"Dobrovolskaia","year":"2008","journal-title":"Mol. Pharm."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"3205","DOI":"10.1002\/jps.24116","article-title":"Dual Drug Release from Core-Shell Nanoparticles with Distinct Release Profiles","volume":"103","author":"Cao","year":"2014","journal-title":"J. Pharm. Sci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.jconrel.2014.03.026","article-title":"PEG-PLGA copolymers: Their structure and structure-influenced drug delivery applications","volume":"183","author":"Zhang","year":"2014","journal-title":"J. Control. Release"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1080\/10717544.2017.1388451","article-title":"Cleavable PEGylation: A strategy for overcoming the \"PEG dilemma\" in efficient drug delivery","volume":"24","author":"Fang","year":"2017","journal-title":"Drug Deliv."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"10748","DOI":"10.1039\/D1NR02065J","article-title":"Effects of polyethylene glycol on the surface of nanoparticles for targeted drug delivery","volume":"13","author":"Shi","year":"2021","journal-title":"Nanoscale"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"67309","DOI":"10.3389\/fphar.2021.673209","article-title":"Nanotechnology-Based Celastrol Formulations and Their Therapeutic Applications","volume":"12","author":"Wagh","year":"2021","journal-title":"Front. Pharmacol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"984","DOI":"10.1039\/D1BM01637G","article-title":"Biodegradable celastrol-loaded albumin nanoparticles ameliorate inflammation and lipid accumulation in diet-induced obese mice","volume":"10","author":"Fan","year":"2022","journal-title":"Biomater. Sci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1039\/C6PY01883A","article-title":"Well-defined podophyllotoxin polyprodrug brushes: Preparation via RAFT polymerization and evaluation as drug carriers","volume":"8","author":"Guo","year":"2017","journal-title":"Polym. Chem."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Yu, B., Wang, X., Ding, L., Han, M., and Guo, Y. (2022). Hydrophilic Natural Polylysine as Drug Nanocarrier for Preparation of Helical Delivery System. Pharmaceutics, 14.","DOI":"10.3390\/pharmaceutics14112512"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1186\/s40824-022-00329-8","article-title":"Ginsenoside Rg3 nanoparticles with permeation enhancing based chitosan derivatives were encapsulated with doxorubicin by thermosensitive hydrogel and anti-cancer evaluation of peritumoral hydrogel injection combined with PD-L1 antibody","volume":"26","author":"Wu","year":"2022","journal-title":"Biomater. Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"8851","DOI":"10.1038\/s41598-020-65773-9","article-title":"Preparation of high drug-loading celastrol nanosuspensions and their anti-breast cancer activities in vitro and in vivo","volume":"10","author":"Huang","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2665","DOI":"10.1021\/acs.molpharmaceut.8b00190","article-title":"Amphiphilic Hybrid Dendritic-Linear Molecules as Nanocarriers for Shape-Dependent Antitumor Drug Delivery","volume":"15","author":"Guo","year":"2018","journal-title":"Mol. Pharm."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/28\/3\/1040\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:11:54Z","timestamp":1760119914000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/28\/3\/1040"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,20]]},"references-count":39,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2023,2]]}},"alternative-id":["molecules28031040"],"URL":"https:\/\/doi.org\/10.3390\/molecules28031040","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,20]]}}}