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This study reports Bola/IM, a nanoformulation where a bola-amphiphilic dendrimer encapsulates imatinib to target CD117 (c-Kit) as a key mediator of ovarian cancer stem cells. Bola/IM more effectively suppresses survival, stemness, and metastasis through a tumor-specific β-catenin/HRP2 signaling axis. Results in patient-derived ascites and organoids, and mouse models show tumor-oriented accumulation, favorable pharmacokinetics, and synergy with cisplatin without adverse effects.",{"@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/bola-amphiphilic-dendrimer-enhances-imatinib-to-target-metastatic-ovarian-cancer-via-catenin-hrp2-signaling-axis/368163/",{"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/bola-amphiphilic-dendrimer-enhances-imatinib-to-target-metastatic-ovarian-cancer-via-catenin-hrp2-signaling-axis/368163.png","ImageObject",300,407,{"name":92,"@type":93},"Patrick","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-24","2026-09-23",true,{"@type":102,"interactionType":103,"userInteractionCount":24},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"Why is ovarian cancer difficult to treat in advanced metastatic cases?","Question",{"text":112,"@type":113},"Ovarian cancer is often diagnosed at an advanced metastatic stage, and platinum/taxane chemotherapy is hindered by intrinsic and acquired chemoresistance, leading to recurrence and poor survival.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"What is Bola/IM and how does it target ovarian cancer stem cells?",{"text":117,"@type":113},"Bola/IM is a nanoformulation of imatinib encapsulated by a bola-amphiphilic dendrimer, designed to target CD117 (c-Kit), a critical mediator of ovarian cancer stem cells.",{"name":119,"@type":110,"acceptedAnswer":120},"What mechanism does the study propose for Bola/IM’s enhanced effects?",{"text":121,"@type":113},"Bola/IM enhances targeting and suppresses survival, stemness, and metastasis through a novel, tumor-specific β-catenin/HRP2 axis.","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},368163,1790488336,{"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":24,"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},549758146520,"https://ap-avatar.wpscdn.com/avatar/80002397d8c0411e94?_k=1775819394049821470","This article is licensed under CC-BY-NC-ND 4.0   \n[www.acsami.org](www.acsami.org)  Research Article   \nBola-Amphiphilic Dendrimer Enhances Imatinib to Target Metastatic Ovarian Cancer via β‑Catenin-HRP2 Signaling Axis  \nZeyu Shi,◆ Margarita Artemenko,◆ Weiyu Yu, Ming Zhang, Canhui Yi, Peng Chen, Shuting Lin, Zhancun Bian, Baoping Lian, Fanzhen Meng, Jiaxuan Chen, Tom Roussel, Ying Li, Karen K. L. Chan, Philip P. C. Ip, Hung-Cheng Lai, Sally K. Y. To, Xiaoxuan Liu, * Ling Peng, * and Alice S. T. Wong*  \n Cite This: ACS Appl. Mater. Interfaces 2025, 17, 2884−2898  \nRead Online  \n\n|  |  |  |  |  |  |\n| --- | --- | --- | --- | --- | --- |\n| ACCESS   | Metrics & More |  |  Article Recommendations |  | *sı Supporting Information |\n\nABSTRACT: Ovarian cancer is the leading cause of death among all gynecological malignancies, and drug resistance renders the current chemotherapy agents ineffective for patients with advanced metastatic tumors. We report an effective treatment strategy for targeting metastatic ovarian cancer involving a nanoformulation (Bola/IM)􀀁bola-amphiphilicdendrimer (Bola)-encapsulated imatinib (IM)􀀁to target the critical mediator of ovarian cancer stem cells (CSCs) CD117 (c-Kit). Bola/IM offered significantly more effective targeting of CSCs compared to IM alone, through a novel and tumor-specific β-catenin/HRP2 axis, allowing potent inhibition of cancer cell survival, stemness, and metastasis in metastatic and drug-resistant ovarian cancer cells. Promising results were also obtained in clinically relevant patient-derived ascites and organoids alongside high  \ntumor-oriented accumulation and favorable pharmacokinetic properties in mouse models. Furthermore, Bola/IM displayed synergistic anticancer activity when combined with the first-line chemotherapeutic drug cisplatin in patient-derived xenograft mouse models without any adverse effects. Our findings support the use of Bola/IM as a nanoformulation to empower IM, providing targeted and potent treatment of metastatic ovarian cancer. Our study thus represents a significant advancement toward addressing the unmet medical need for improved therapies targeting this challenging disease.  \nKEYWORDS: cancer stem cells, targeted therapy, dendrimer, nanovector, chemoresistance, ovarian cancer  \n1. INTRODUCTION  \nOvarian cancer is the most lethal gynecological malignancy worldwide.1,2 Being asymptomatic, more than 75% of ovarian cancer cases are diagnosed at an advanced metastatic stage.3 Platinum/taxane-based chemotherapy is the first-line standard approach used for treating unresectable ovarian cancer4 but is greatly hindered by intrinsic and acquired chemoresistance. While metastatic tumors are initially sensitive to this chemotherapy, 70% ofpatients will experience recurrence, which is the major cause of mortality, with a 5-year survival rate of \u003C25%.5 Thus, there is an urgent need for new therapeutic strategies that can provide increased specificity and efficacy in treating metastatic drug-resistant ovarian cancer.  \nCancer stem cells (CSCs) are a small subpopulation of tumor cells that possess a high capacity for self-renewal and multilineage differentiation, tumor initiation, chemoresistance, and metastasis.6 As such, targeting CSCs represents a critically important strategy in treating metastatic, chemoresistant cancers. We have reported a critical role for receptor tyrosine kinase c-Kit (also known as CD117) in CSCs. Not only does cKit serve as a marker of ovarian CSCs, but it also determines their stem phenotype.7 While activating c-Kit mutations have not been found in ovarian cancer, increased c-Kit expression has  \nbeen correlated with poorer patient outcomes.7 Moreover, c-Kit is hyperactivated in tumor-infiltrating immune cells,8 suggesting that targeting c-Kit may also relieve immunosuppression in the tumor microenvironment.  \nOne ideal candidate for targeting c-Kit is imatinib (IM, Scheme 1a), an FDA-approved anticancer drug shown to inhibit c-Kit, Bcr/Abl, a","cbCailzeW2pIqrUP","https://ap.wps.com/l/cbCailzeW2pIqrUP","pdf",14213720,15,"English","# Abstract\n# Introduction\n## Rationale for targeting ovarian cancer stem cells\n## Limitations of imatinib-based therapy","[{\"question\":\"Why is ovarian cancer difficult to treat in advanced metastatic cases?\",\"answer\":\"Ovarian cancer is often diagnosed at an advanced metastatic stage, and platinum/taxane chemotherapy is hindered by intrinsic and acquired chemoresistance, leading to recurrence and poor survival.\"},{\"question\":\"What is Bola/IM and how does it target ovarian cancer stem cells?\",\"answer\":\"Bola/IM is a nanoformulation of imatinib encapsulated by a bola-amphiphilic dendrimer, designed to target CD117 (c-Kit), a critical mediator of ovarian cancer stem cells.\"},{\"question\":\"What mechanism does the study propose for Bola/IM’s enhanced effects?\",\"answer\":\"Bola/IM enhances targeting and suppresses survival, stemness, and metastasis through a novel, tumor-specific β-catenin/HRP2 axis.\"}]","Bola-Amphiphilic Dendrimer Enhances Imatinib to Target Metastatic Ovarian Cancer via β-Catenin-HRP2 Signaling Axis | PDF",1790175366,38]