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Encapsulation efficiencies for GEM and HNK in SDC1-LB-MSN-GEM/HNK were 60.3 ± 3.2% and 73.0 ± 1.1%. Targeting efficiency was evaluated in BxPC-3 cells, showing a 2-fold fluorescence increase due to SDC1/IGF1R-mediated endocytosis, accompanied by markedly enhanced cytotoxicity. Mechanistic studies indicated SDC1-LB-MSN-HNK induced tumor apoptosis via the mitochondrial pathway, and in BALB/c nude mice it achieved tumor growth inhibition of 56.19%, outperforming free GEM/HNK and LB-MSN-GEM/HNK groups, with preliminary safety supported.",{"@graph":69,"@context":123},[70,84,106],{"@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/co-delivery-of-gemcitabine-and-honokiol-by-lipid-bilayer-coated-mesoporous-silica-nanoparticles-enhances-pancreatic-cancer-therapy-via-targeting-depletion-of-tumor-stroma/330089/",{"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/co-delivery-of-gemcitabine-and-honokiol-by-lipid-bilayer-coated-mesoporous-silica-nanoparticles-enhances-pancreatic-cancer-therapy-via-targeting-depletion-of-tumor-stroma/330089.png","ImageObject",300,407,{"name":92,"@type":93},"Himbo","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-24","2026-09-21",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",15,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"What delivery system was used to co-deliver gemcitabine and honokiol?","Question",{"text":113,"@type":114},"Syndecan-1 modified lipid bilayer-coated mesoporous silica nanoparticles (SDC1-LB-MSN) were prepared to co-deliver gemcitabine (GEM) and honokiol (HNK).","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"How was targeting efficiency evaluated in vitro?",{"text":118,"@type":114},"Targeting efficiency was investigated in BxPC-3 cells by measuring fluorescence intensity, where SDC1/IGF1R-mediated endocytosis increased intracellular fluorescence about 2-fold versus LB-MSN controls.",{"name":120,"@type":111,"acceptedAnswer":121},"What therapeutic effects were observed in vivo and how did they compare to other treatments?",{"text":122,"@type":114},"In BALB/c nude mice bearing BxPC-3 tumors, SDC1-LB-MSN-GEM/HNK produced a tumor growth inhibition index of 56.19%, which was higher than free GEM/HNK (1.45-fold) and LB-MSN-GEM/HNK (1.33-fold), with preliminary safety also assessed.","https://schema.org",{"og:url":83,"og:type":125,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":127,"canonical":83},"index,follow",{"doc_id":129,"site_id":62},330089,1790133330,{"code":4,"msg":5,"data":132},{"doc_id":129,"user_id":133,"nickname":92,"user_avatar":134,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":105,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":140,"language":141,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":142,"faqs":143,"seo_title":144,"seo_description":67,"update_tm":145,"read_time":36},687197100911,"https://ap-avatar.wpscdn.com/avatar/a000239b6f1da00475?x-image-process=image/resize,m_fixed,w_180,h_180&k=1785132997149421697","molecules   \nArticle  \nCo-Delivery of Gemcitabine and Honokiol by Lipid Bilayer-Coated Mesoporous Silica Nanoparticles Enhances Pancreatic Cancer Therapy via Targeting Depletion of Tumor Stroma  \nDan Liu, Linjiang Wang, Henan Li, Dong Li, Jianwen Zhou, Jing Wang, Qi Zhang * and Defu Cai *  \nCitation: Liu, D.; Wang, L.; Li, H.; Li, D.; Zhou, J.; Wang, J.; Zhang, Q.; Cai, D. Co-Delivery of Gemcitabine and Honokiol by Lipid Bilayer-Coated Mesoporous Silica Nanoparticles Enhances Pancreatic Cancer Therapy via Targeting Depletion of Tumor Stroma. Molecules 2024, 29, 675 . [https://doi.org/10.3390/](https://doi.org/10.3390/)[ ](https://doi.org/10.3390/)molecules29030675  \nAcademic Editor: Fabio Sonvico  \nReceived: 15 January 2024  \nRevised: 29 January 2024  \nAccepted: 30 January 2024  \nPublished: 31 January 2024  \nCopyright: © 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) .  \nInstitute of Medicine and Drug Research, Qiqihar Medical University, Qiqihar 161006, China;  \n[liudan@qmu.edu.cn](liudan@qmu.edu.cn) (D.L.); [lingjiangwang6@gmail.com](lingjiangwang6@gmail.com) (L.W.); [henanli0902@gmail.com](henanli0902@gmail.com) (H.L.);  \n[lidong201809@gmail.com](lidong201809@gmail.com) (D.L.); [zhoujianwen@qmu.edu.cn](zhoujianwen@qmu.edu.cn) (J.Z.); [wangjing@qmu.edu.cn](wangjing@qmu.edu.cn) (J.W.)  \n* Correspondence: [zhangqi@qmu.edu.cn](zhangqi@qmu.edu.cn) (Q.Z.); [cai@qmu.edu.cn](cai@qmu.edu.cn) (D.C.)  \nAbstract: Syndecan-1 (SDC1) modified lipid bilayer (LB)-coated mesoporous silica nanoparticles (MSN) to co-deliver gemcitabine (GEM) and honokiol (HNK) were prepared for the targeting treatment of pancreatic cancer. The encapsulation efficiencies of GEM and HNK in SDC1-LB-MSNGEM/HNK were determined to be 60.3 ± 3.2% and 73.0 ± 1.1% . The targeting efficiency of SDC1-LB-MSN-GEM/HNK was investigated in BxPC-3 cells in vitro. The fluorescence intensity in the cells treated with SDC1-LB-MSN-Cou6 was 2-fold of LB-MSN-Cou6-treated cells, which was caused by SDC1/IGF1R-mediated endocytosis. As anticipated, its cytotoxicity was significantly increased. Furthermore, the mechanism was verified that SDC1-LB-MSN-HNK induced tumor cell apoptosis through the mitochondrial apoptosis pathway. Finally, the biodistribution, tumor growth inhibition, and preliminary safety studies were performed on BALB/c nude mice bearing BxPC-3 tumor models. The tumor growth inhibition index of SDC1-LB-MSN-GEM/HNK was 56.19%, which was 1.45-fold and 1.33-fold higher than that of the free GEM/HNK and LB-MSN-GEM/HNK treatment groups, respectively. As a result, SDC1-LB-MSN-GEM/HNK combined advantages of both GEM and HNK and simultaneously targeted and eliminated pancreatic cancerous and cancer-associated stromal cells. In summary, the present study demonstrated a new strategy of synergistic GEM and HNK to enhance the therapeutic effect of pancreatic cancer via the targeting depletion of tumor stroma.  \nKeywords: gemcitabine; honokiol; lipid bilayer-coated mesoporous silica nanoparticles; syndecan-1; targeting tumor stroma  \n1. Introduction  \nGemcitabine (GEM), a nucleoside analogue, is a first-line chemotherapy drug for pancreatic cancer. However, the median survival was 6.8 months and the objective response rate was 9.4% for GEM-treated patients [1] . The reason for the worse prognosis of pancreatic cancer in clinic is the resistance to GEM [2] . This resistance resulted mainly from the stroma of pancreatic cancer in which tumor cell clusters are wrapped by a dense, interconnected stromal structure, creating physical barriers to prevent GEM from penetrating and accumulating in the tumor cells [3,4] . Insufficient activation or rapid inactivation may lead to unfavorable GEM pharmacok","cbCaibk2ENjeabRv","https://ap.wps.com/l/cbCaibk2ENjeabRv","pdf",3506854,16,"English","# Abstract\n# Keywords\n# 1. Introduction","[{\"question\":\"What delivery system was used to co-deliver gemcitabine and honokiol?\",\"answer\":\"Syndecan-1 modified lipid bilayer-coated mesoporous silica nanoparticles (SDC1-LB-MSN) were prepared to co-deliver gemcitabine (GEM) and honokiol (HNK).\"},{\"question\":\"How was targeting efficiency evaluated in vitro?\",\"answer\":\"Targeting efficiency was investigated in BxPC-3 cells by measuring fluorescence intensity, where SDC1/IGF1R-mediated endocytosis increased intracellular fluorescence about 2-fold versus LB-MSN controls.\"},{\"question\":\"What therapeutic effects were observed in vivo and how did they compare to other treatments?\",\"answer\":\"In BALB/c nude mice bearing BxPC-3 tumors, SDC1-LB-MSN-GEM/HNK produced a tumor growth inhibition index of 56.19%, which was higher than free GEM/HNK (1.45-fold) and LB-MSN-GEM/HNK (1.33-fold), with preliminary safety also assessed.\"}]","Co-Delivery of Gemcitabine and Honokiol by Lipid Bilayer-Coated Mesoporous Silica Nanoparticles Enhances Pancreatic Cancer Therapy via Targeting Depletion of Tumor Stroma | PDF",1789987069]