[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-379865-105":59,"doc-detail-379865-en":130},{"code":4,"msg":5,"data":6},0,"success",[7,13,18,23,28,33,38,43,48,51,55],{"id":8,"doc_module":4,"doc_module_name":9,"category_name":10,"show_sort_weight":11,"slug":12},1,"Document","Story & Novel",90,"story-novel",{"id":14,"doc_module":4,"doc_module_name":9,"category_name":15,"show_sort_weight":16,"slug":17},2,"Literature",80,"literature",{"id":19,"doc_module":4,"doc_module_name":9,"category_name":20,"show_sort_weight":21,"slug":22},4,"Exam",70,"exam",{"id":24,"doc_module":4,"doc_module_name":9,"category_name":25,"show_sort_weight":26,"slug":27},5,"Comic",60,"comic",{"id":29,"doc_module":4,"doc_module_name":9,"category_name":30,"show_sort_weight":31,"slug":32},6,"Technology",50,"technology",{"id":34,"doc_module":4,"doc_module_name":9,"category_name":35,"show_sort_weight":36,"slug":37},7,"Healthcare",40,"healthcare",{"id":39,"doc_module":4,"doc_module_name":9,"category_name":40,"show_sort_weight":41,"slug":42},8,"Research & Report",30,"research-report",{"id":44,"doc_module":4,"doc_module_name":9,"category_name":45,"show_sort_weight":46,"slug":47},9,"Religion & Spirituality",20,"religion-spirituality",{"id":46,"doc_module":4,"doc_module_name":9,"category_name":49,"show_sort_weight":46,"slug":50},"World Cup","world-cup",{"id":52,"doc_module":4,"doc_module_name":9,"category_name":53,"show_sort_weight":52,"slug":54},10,"Lifestyle","lifestyle",{"id":56,"doc_module":4,"doc_module_name":9,"category_name":57,"show_sort_weight":24,"slug":58},19,"General","general",{"code":4,"msg":60,"data":61},"ok",{"site_id":62,"language":63,"slug":64,"title":65,"keywords":66,"description":67,"schema_data":68,"social_meta":123,"head_meta":125,"extra_data":127,"updated_unix":129},105,"en","hyaluronidase-trigger-nanocarriers-for-targeted-delivery-of-anti-liver-cancer-compound","Hyaluronidase-trigger nanocarriers for targeted delivery of anti-liver cancer compound","","Chemotherapy is a major option for liver cancer, yet the anti-liver compound celastrol is hindered by systemic toxicity, poor water solubility, multidrug resistance, premature degradation, and insufficient tumor targeting. This study develops hyaluronidase (HAase)-responsive HA/(MI)7-b-CD nanocarriers that exploit CD44-rich liver cancer cells. Under HAase stimulation, the nanocarriers disassemble to trap, deliver, and controllably release celastrol. Cytotoxicity and uptake experiments show reduced toxicity to normal cells and effective inhibition and apoptosis in tumor cells, with release behavior consistent with free drug performance.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/hyaluronidase-trigger-nanocarriers-for-targeted-delivery-of-anti-liver-cancer-compound/379865/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/hyaluronidase-trigger-nanocarriers-for-targeted-delivery-of-anti-liver-cancer-compound/379865.png","ImageObject",300,407,{"name":92,"@type":93},"Ivy","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-09-25","2026-09-24",true,{"@type":102,"interactionType":103,"userInteractionCount":81},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"Why is celastrol limited in liver cancer chemotherapy?","Question",{"text":112,"@type":113},"Its clinical use is restricted by systemic toxicity, poor water solubility, multidrug resistance, premature degradation, and lack of tumor targeting.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How do the HA/(MI)7-b-CD nanocarriers achieve targeted delivery?",{"text":117,"@type":113},"They are designed around HA/HAase biology, taking advantage of CD44 receptors on liver cancer cells and HAase-triggered disassembly to release celastrol where needed.",{"name":119,"@type":110,"acceptedAnswer":120},"What evidence supports the effectiveness of the nanocarrier-delivered celastrol?",{"text":121,"@type":113},"Cytotoxicity assays show reduced toxicity for normal cells and strong inhibition of tumor cell survival, including apoptosis effects comparable to free celastrol at the tested concentration.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},379865,1790355903,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":81,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145},549758252649,"https://ap-avatar.wpscdn.com/avatar/8000253669c5317157?_k=1778319167496531819","RSC Advances  \nPAPER  \nCite this: RSC Adv., 2023, 13, 11160  \nReceived 1st February 2023  \nAccepted 30th March 2023 DOI: 10.1039/d3ra00693j[rsc.li/rsc-advances](rsc.li/rsc-advances)  \nHyaluronidase-trigger nanocarriers for targeted delivery of anti-liver cancer compound†  \nJunxin Xu,a Siling Chen,a Jianmei Yang,a Zhengquan Nie,a Junnan He,a Yong Zhao,a Xiaoqing Liu,b Jin Zhang*a and Yan Zhao  *a  \nChemotherapy is recognized as one of the significant treatment methods for liver cancer. The compound celastrol (CSL) could effectively inhibit the proliferation, migration, and invasion of liver cancer cells, which is regarded as a promising candidate to become a mainstream anti-liver cancer drug. However, the application of CSL in liver cancer chemotherapy is limited due to its systemic toxicity, poor water solubility, multidrug resistance, premature degradation, and lack of tumor targeting. Meanwhile, in order to comply with the current concept of precision medicine, precisely targeted delivery of the anti-liver compound CSL was desired. This paper takes into account that liver cancer cells were equipped with hyaluronic acid (HA) receptors (CD44) on their surface and overexpressed. Hyaluronidase (HAase) capable of degrading HA, HAase-responsive nanocarriers (NCs), named HA/(MI)7-b-CD NCs, were prepared based on the electrostatic interaction between HA and imidazole moieties modified bcyclodextrin (MI)7-b-CD. HA/(MI)7-b-CD NCs showed disassembly properties under HAase stimuli, which was utilized to trap, deliver, and the controllable release of the anti-liver cancer compound CSL. Furthermore, cytotoxicity assay experiments revealed that CSL-trapped HA/(MI)7-b-CD NCs not only reduced cytotoxicity for normal cells but also effectively inhibited the survival for five tumor cells, and even the apoptotic effect of CSL-trapped NCs with a concentration of 5 mg mL −1 on tumor cells (SMMC- 7721) was consistent with free CSL. Cell uptake experiments demonstrated HA/(MI)7-b-CD NCs possessed the capability of targeted drug delivery to cancerous cells. HA/(MI)7-b-CD NCs exhibited sitespecific and controllable release performance, which is anticipated to proceed further in precisiontargeted drug delivery systems.  \n1 Introduction  \nLiver cancer is one of the most frequently diagnosed solid tumors worldwide and the third leading cause of cancer-related deaths.1 In addition, liver cancer is the only one of the top 􀀁ve most lethal cancers to show an annual percentage increase in occurrence.2 In recent decades, the effective treatment of liver cancer has become one of the clinical challenges arising from the growing number of liver cancer cases. Chemotherapy is considered to be one of the most effective treatments for liver cancer.3 Traditional Chinese medicine (TCM) has become a research hotspot in the 􀀁eld of chemotherapy drugs because it can act on preventing tumorigenesis attenuating toxicity, enhancing the treatment effect, and reducing tumor recurrence and metastasis. Among them, celastrol (CSL) is a natural active product extracted from the root bark of Tripterygium wilfordii  \naCollege of Chemistry and Chemical Engineering, Yunnan Normal University, Kunming, 650500, People's Republic of China. E-mail: [ynzhangjin@163.com](ynzhangjin@163.com); [zhaooyann@163.com](zhaooyann@163.com)  \nbShenzhen Kewode Technology Co., Ltd, Shenzhen, 518028, People's Republic of China † Electronic supplementary information (ESI) available. See DOI:  \n[https://doi.org/10.1039/d3ra00693j](https://doi.org/10.1039/d3ra00693j)  \nHook, which displays strong antioxidant, anti-cancer, antirheumatoid and other effects.4–7 In clinical practice, CSL has been successfully used to treat autoimmune diseases such as rheumatoid arthritis and leprosy reactions.8,9 It is worth mentioning that recent research has demonstrated that CSL caneffectively inhibit the proliferation, metastasis, and invasion of liver cancer cells.10 However, CSL is limited use in hepatocellular carcinoma chemotherapy","cbCaiv8kThxRqIUw","https://ap.wps.com/l/cbCaiv8kThxRqIUw","pdf",1166896,11,"English","# 1 Introduction\n## Liver cancer treatment challenges and celastrol limitations\n## Precision medicine and targeted delivery rationale\n## Stimulus-responsive and enzyme-responsive drug delivery systems\n## Role of hyaluronidase and HA receptors (CD44/RHAMM) in targeting","[{\"question\":\"Why is celastrol limited in liver cancer chemotherapy?\",\"answer\":\"Its clinical use is restricted by systemic toxicity, poor water solubility, multidrug resistance, premature degradation, and lack of tumor targeting.\"},{\"question\":\"How do the HA/(MI)7-b-CD nanocarriers achieve targeted delivery?\",\"answer\":\"They are designed around HA/HAase biology, taking advantage of CD44 receptors on liver cancer cells and HAase-triggered disassembly to release celastrol where needed.\"},{\"question\":\"What evidence supports the effectiveness of the nanocarrier-delivered celastrol?\",\"answer\":\"Cytotoxicity assays show reduced toxicity for normal cells and strong inhibition of tumor cell survival, including apoptosis effects comparable to free celastrol at the tested concentration.\"}]","Hyaluronidase-trigger nanocarriers for targeted delivery of anti-liver cancer compound | PDF",1790237811,28]