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Antibody-drug conjugates have advanced clinical testing, motivating DNA nanostructure–based delivery. The study constructs a rituximab–DNA tetrahedron–doxorubicin conjugate (RTD) using DNA tetrahedra for loading and coupling, validating strong in vitro anticancer activity. In a subcutaneous tumor model, RTD maintains potent efficacy while reducing doxorubicin-associated cardiotoxicity and hematotoxicity, supporting next-generation ADC development.",{"@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/antibody-dna-nanostructure-conjugates-integrate-doxorubicin-and-rituximab-to-enhance-therapeutic-efficacy-for-dlbcl-drug-advances/435409/",{"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/antibody-dna-nanostructure-conjugates-integrate-doxorubicin-and-rituximab-to-enhance-therapeutic-efficacy-for-dlbcl-drug-advances/435409.png","ImageObject",300,407,{"name":92,"@type":93},"pop out","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-30","2026-09-29",true,{"@type":102,"interactionType":103,"userInteractionCount":34},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"Why is R-CHOP challenging for many DLBCL patients?","Question",{"text":112,"@type":113},"A substantial fraction of patients relapse and show poor survival after R-CHOP, and the regimen’s high chemotherapy burden can cause severe toxic side effects.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"What conjugate design does the study develop?",{"text":117,"@type":113},"It fabricates an antibody-DNA nanostructure conjugate by combining a rituximab-based R-CHOP component with DNA tetrahedra, then loading doxorubicin to form the RTD conjugate.",{"name":119,"@type":110,"acceptedAnswer":120},"What evidence supports RTD’s improved therapeutic profile?",{"text":121,"@type":113},"RTD shows robust antitumor effects in vitro, exceeding the combined effects of rituximab and doxorubicin by over 50-fold, and retains strong efficacy in a subcutaneous tumor model while mitigating doxorubicin cardiotoxicity and hematotoxicity.","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},435409,1790795002,{"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":34,"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,"preview_page_count":4},962090760408,"https://ap-avatar.wpscdn.com/davatar_085a072bc5b1113ac321206ff7593b45","DRUG ADVANCES  \nAntibody-DNA nanostructure conjugates integrate doxorubicin andrituximab to enhance therapeutic efficacy for DLBCL  \nZuguang Xia, 1, 2,* Jiazhen Cao,3,* Yingzhu Li,4 Jianing Wu,4 Jun Ren,4 Weiqi Sheng,2,5,6 Chengxun Li,7 and Shengjie Li4  \n1 Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China; 2 Department of Oncology, Shanghai Medical College, 3 Department of Laboratory Medicine, Huashan Hospital, and 4 Department of Clinical Laboratory, Eye & ENT Hospital, Shanghai Medical College, Fudan University, Shanghai, China;  \n5 Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China; and 6 Institute of Pathology, and 7 Department of Otolaryngology, Eye & ENT Hospital, Fudan University, Shanghai, China  \nThe primary clinical approach for diffuse large B-cell lymphoma (DLBCL) in recent decades has predominantly relied on chemotherapy with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) as the cornerstone. However, given the highly heterogeneous nature of DLBCL, >30% of patients are prone to relapse and may even exhibit resistance to treatment. Antibody-drug conjugate (ADC) therapies have demonstrated significant advancements in clinical trials targeting DLBCL, thereby indicating a promising direction for its management. By leveraging the inherent modifiability of DNA nanostructures and the affinity of doxorubicin for DNA, we used a combination of rituximab-based R-CHOP scheme and DNA tetrahedra to fabricate antibody-DNA nanostructure conjugate (ADNC). Therituximab-tetrahedron-doxorubicin conjugate (RTD) studied in our research has been validated through in vitro cellular experiments and subcutaneous tumor models. The RTD demonstrated a robust antitumor effect in vitro, significantly exceeding the combined effects of rituximab and doxorubicin by >50-fold. Furthermore, confirmation from a subcutaneous tumor model substantiated the potent antitumor efficacy of RTD while successfully mitigating cardiotoxicity and hematotoxicity associated with doxorubicin. ADNC effectively facilitates the binding of rituximab and doxorubicin in the R-CHOP regimen, offering novel prospects for the development of next-generation ADC drugs.  \nIntroduction  \nDiffuse large B-cell lymphomas (DLBCLs), accounting for ~30% of all non-Hodgkin lymphoma cases worldwide and affecting ~150 000 individuals annually, typically manifest as progressive lymphadenopathy or extranodal disease.1 Despite most patients being diagnosed at an advanced stage, >60% can achieve a cure through the administration of R-CHOP (rituximab [RTM], cyclophosphamide, doxorubicin [DOX], vincristine, and prednisone) immunochemotherapy.1 Currently, DLBCL treatment encounters 2 primary challenges: first, 40% of patients still experience relapse and exhibit poor survival outcomes after R-CHOP therapy2 ; and second, the R-CHOP–based treatment regimen using a substantial quantity of chemotherapy drugs may induce severe toxic side effects in patients.3 Therefore, the development of novel therapeutic strategies is currently an imperative.  \nSubmitted 12 May 2025; accepted 30 August 2025; prepublished online on Blood Advances First Edition 30 September 2025. [https://doi.org/10.1182/](https://doi.org/10.1182/)[ ](https://doi.org/10.1182/)[bloodadvances.2025017118](bloodadvances.2025017118.)[.](bloodadvances.2025017118.)  \n*Z.X. and J.C. contributed equally to this work.  \nThe data generated in this study are available within the article and its supplemental Data files.  \nThe full-text version of this article contains a data supplement.  \n© 2025 American Society of Hematology. Published by Elsevier Inc. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.  \n23 DECEMBER 2025 • VOLUME 9, NUMBER 24 6549  \nIn the POLARIX phase 3 study, the addition of th","cbCaiaMWZrOtwwO0","https://ap.wps.com/l/cbCaiaMWZrOtwwO0","pdf",9368121,14,"English","# Introduction\n## R-CHOP limitations in DLBCL\n## Rationale for antibody-drug conjugates (ADCs)\n## DNA tetrahedra as a drug-delivery platform","[{\"question\":\"Why is R-CHOP challenging for many DLBCL patients?\",\"answer\":\"A substantial fraction of patients relapse and show poor survival after R-CHOP, and the regimen’s high chemotherapy burden can cause severe toxic side effects.\"},{\"question\":\"What conjugate design does the study develop?\",\"answer\":\"It fabricates an antibody-DNA nanostructure conjugate by combining a rituximab-based R-CHOP component with DNA tetrahedra, then loading doxorubicin to form the RTD conjugate.\"},{\"question\":\"What evidence supports RTD’s improved therapeutic profile?\",\"answer\":\"RTD shows robust antitumor effects in vitro, exceeding the combined effects of rituximab and doxorubicin by over 50-fold, and retains strong efficacy in a subcutaneous tumor model while mitigating doxorubicin cardiotoxicity and hematotoxicity.\"}]","Antibody-DNA nanostructure conjugates integrate doxorubicin and rituximab to enhance therapeutic efficacy for DLBCL - Drug Advances | PDF",1790673507,35]