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Clinical databases assess DR6 expression and its association with patient survival, and DP7-C/siDR6 micelles are prepared by self-assembly. In vitro assays in 293T, B16F10, and LL2 cells evaluate transfection efficiency, safety, and anti-tumor activity, while mouse studies test lung targeting, metastatic prevention, and therapeutic efficacy across LL2, B16F10, and 4T1 models. Results show DR6 enrichment in metastatic tumors, STAT3 suppression, efficient lung targeting, and blockade of endothelial necroptosis-driven metastasis, supporting an alternative systemic delivery strategy.",{"@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/a-novel-systemic-sidr6-delivery-system-based-on-dp7-c-for-the-treatment-of-metastatic-lung-cancer/371344/",{"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/a-novel-systemic-sidr6-delivery-system-based-on-dp7-c-for-the-treatment-of-metastatic-lung-cancer/371344.png","ImageObject",300,407,{"name":92,"@type":93},"Riley","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-24","2026-09-23",true,{"@type":102,"interactionType":103,"userInteractionCount":39},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What problem does this study address in metastatic lung cancer?","Question",{"text":112,"@type":113},"It targets the limited effectiveness of conventional therapies and the clinical need for an effective, minimally invasive strategy to prevent and treat lung metastases.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How are DP7-C/siDR6 micelles prepared and evaluated?",{"text":117,"@type":113},"DP7-C/siDR6 micelles are generated by self-assembly. 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Once lung metastasis occurs, patients’ survival is often significantly shortened. Therefore, prevention and treatment of lung metastases is an important aspect of cancer treatment. In this study, a simple, low-toxicity, cholesterol-modified cationic cell-penetrating peptide DP7 (DP7-C), in combination with siDR6 was used for intravenous administration for the treatment of lung metastases.\u003Cbr>Methods: Initially, clinical databases were analyzed to determine the expression levels of death receptor 6 (DR6) in metastatic tumorsand the correlation between DR6 expression and patient survival times. The DP7-C/siDR6 micelles were prepared by a self-assembly method. By cultivating 293T, B16F10 and LL2 cells, the in vitro experiments were performed to assess the transfection efficiency, safety and anti-cancer ability of DP7-C/siDR6, while its targeting efficiency and prevention of lungs were investigated by mouse experiments. Furthermore, the therapeutic efficacy of DP7-C/siDR6 was demonstrated in the LL2 model of lung cancer in situ, the B16F10 model of artificial lung metastasis, and the 4T1 model of spontaneous lung metastasis.\u003Cbr>Results: The clinical data analysis revealed that DR6 was highly expressed in the majority of metastatic tumors and that patients with high DR6 expression exhibited significantly shorter survival times. The DP7-C/siDR6 showed high transfection efficiency, and it could inhibit tumor cell growth by suppressing the STAT3 signaling pathway. Subsequent mouse experiments demonstrated that intravenous administration of DP7-C/siDR6 resulted in efficient lung targeting. The inhibition of DR6 expression on lung endothelial cells was found to prevent metastasis-induced primary necrosis of lung endothelial cells, thereby preventing tumor metastasis. And the DP7-C/ siDR6 treatment showed excellent therapeutic efficacy in the tumor models.\u003Cbr>Conclusion: The systemic delivery of DP7-C micelles carrying siDR6 provide an alternative therapeutic strategy to halt cancer lung metastasis.\u003Cbr>Keywords: DP7-C, siDR6, gene therapy, delivery system, metastatic cancer |\n| --- |\n| Introduction\u003Cbr>It has been reported that more than 90% of cancer-related deaths are associated with metastasis.1–3 Metastasis may occur at any stage of the disease, including in multiple cancers such as melanoma, breast cancer, lung cancer, and liver cancer.4–6 Primary cancer cells typically metastasize to the lung, liver, brain, and bone. The lung has emerged as one of the most common metastatic organs for tumor cells due to its rich capillary network and low blood flow pressure.7,8 Given the challenges inherent in the treatment of lung metastasis, approximately 30% of patients with cancer die from this complication.9 While conventional treatments such as surgery, resection, chemotherapy, and radiotherapy exert a therapeutic effect to some extent, the therapeutic benefit of these treatments is unsatisfactory for the majority of |\n\nReceived: 1 September 2024  \nAccepted: 6 March 2025  \nPublished: 19 March 2025  \nInternational Journal of Nanomedicine 2025:20 3623–3642 3623  \n© 2025 Zhou et al. This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at [http","cbCaisHqhd9reJjZ","https://ap.wps.com/l/cbCaisHqhd9reJjZ","pdf",18371459,"English","# Background\n# Methods\n# Results\n# Conclusion\n# Keywords\n# Introduction","[{\"question\":\"What problem does this study address in metastatic lung cancer?\",\"answer\":\"It targets the limited effectiveness of conventional therapies and the clinical need for an effective, minimally invasive strategy to prevent and treat lung metastases.\"},{\"question\":\"How are DP7-C/siDR6 micelles prepared and evaluated?\",\"answer\":\"DP7-C/siDR6 micelles are generated by self-assembly. Transfection efficiency, safety, and anti-cancer activity are assessed in cultured cells, and targeting plus prevention are evaluated in mouse experiments.\"},{\"question\":\"What main biological findings support the therapeutic effect?\",\"answer\":\"DR6 is highly expressed in metastatic tumors and correlates with shorter survival. DP7-C/siDR6 inhibits tumor growth by suppressing STAT3 signaling and achieves lung targeting, helping prevent endothelial cell necroptosis-driven metastasis.\"}]","A Novel Systemic siDR6 Delivery System Based on DP7-C - for the Treatment of Metastatic Lung Cancer | PDF",1790191855]