[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-454609-105":59,"doc-detail-454609-en":131},{"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":124,"head_meta":126,"extra_data":128,"updated_unix":130},105,"en","homing-and-detection-of-unknown-primary-head-neck-cancer-by-acid-sensing-nanoparticles","Homing and Detection of Unknown Primary Head-Neck Cancer by Acid-Sensing Nanoparticles","","Precise localization is essential for curative surgery, yet unknown primary head-and-neck cancer remains difficult to identify when tumors are small or anatomically concealed. This work describes a prospective Phase 2 open-label clinical trial (NCT05576974) using Pegsitacianine, an acid-sensing nanoparticle with activation threshold pH 5.3, to construct a single-cell spatial atlas in head-and-neck squamous carcinoma. Results show preferential accumulation in immune-infiltrative severely acidic milieus (iSAM), enabling fluorescence-guided tumor resection in 14 of 16 patients when standard diagnostics failed. Findings link tumor metabolism, immune infiltration, and nanoparticle delivery, supporting severe tumor acidosis targeting for diagnosis and therapy.",{"@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/homing-and-detection-of-unknown-primary-head-neck-cancer-by-acid-sensing-nanoparticles/454609/",{"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/homing-and-detection-of-unknown-primary-head-neck-cancer-by-acid-sensing-nanoparticles/454609.png","ImageObject",300,407,{"name":92,"@type":93},"วิน","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-07","2026-09-30",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",12,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"Why is unknown primary head-and-neck cancer hard to treat surgically?","Question",{"text":113,"@type":114},"The primary tumor can remain undetectable even when cervical nodal metastases are present, especially when conventional diagnostics cannot locate the source lesion accurately.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"What is Pegsitacianine and what pH threshold does it target?",{"text":118,"@type":114},"Pegsitacianine is an ultra pH-sensitive acid-sensing nanoparticle designed to fluoresce under severe acidic conditions with an activation pH threshold of 5.3.",{"name":120,"@type":111,"acceptedAnswer":121},"How well did Pegsitacianine help detect tumors in the Phase 2 trial?",{"text":122,"@type":114},"In the ILLUMINATE Study, fluorescence-guided resection was achieved in 14 of 16 patients with unknown primary cancer when conventional diagnostic tools failed to locate the tumor.","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},454609,1791394007,{"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":146,"preview_page_count":4},2336475104736,"https://ap-avatar.wpscdn.com/avatar/22000c4c5e0e5b17e70?x-image-process=image/resize,m_fixed,w_180,h_180&k=1786591360781797222","UT Southwestern Medical Center [https://orcid.org/0000-0003-0726-5098](https://orcid.org/0000-0003-0726-5098)  \nThe University of Texas Southwestern Medical Center [https://orcid.org/0000-0002-3665-3914](https://orcid.org/0000-0002-3665-3914)  \nThe University of Texas Southwestern Medical Center [https://orcid.org/0009-0006-4896-8952](https://orcid.org/0009-0006-4896-8952)  \nThe University of Texas Southwestern Medical Center  \nThe University of Texas Southwestern Medical Center  \nThe University of Texas Southwestern Medical Center  \nThe University of Texas Southwestern Medical Center  \nThe University of Texas Southwestern Medical Center  \nThe University of Texas Southwestern Medical Center  \nThe University of Texas Southwestern Medical Center  \nThe University of Texas Southwestern Medical Center  \nThe University of Texas Southwestern Medical Center  \nThe University of Texas Southwestern Medical Center  \nThe University of Texas Southwestern Medical Center  \nThe University of Texas Southwestern Medical Center  \nUniversity of Texas Southwestern Medical Center [https://orcid.org/0000-0001-6658-9557](https://orcid.org/0000-0001-6658-9557)  \nThe University of Texas Southwestern Medical Center  \nThe University of Texas Southwestern Medical Center  \nUT Southwestern Medical Center [https://orcid.org/0000-0001-6754-0480](https://orcid.org/0000-0001-6754-0480)  \nThe University of Texas Southwestern Medical Center  \nUniversity of Texas Southwestern Medical Center [https://orcid.org/0000-0002-3133-6717](https://orcid.org/0000-0002-3133-6717)  \nUniversity of Texas Southwestern Medical Center [https://orcid.org/0000-0002-8371-4388](https://orcid.org/0000-0002-8371-4388)  \nDecember 10th, 2025  \n [https://doi.org/10.21203/rs.3.rs-8253010/v1](https://doi.org/10.21203/rs.3.rs-8253010/v1)  \n 􀁱 􀅏 This work is licensed under a Creative Commons Attribution 4.0 International License.  \nRead Full License  \n there is potential Competing Interest. B. D.S. and J. G. are scienti«c cofounders and scienti«c advisors of OncoNano Medicine, Inc. G. H. is a scienti«c advisor for OncoNano Medicine, Inc.  \nPrecise localization of cancer is essential for curative surgery but remains a major clinical challenge when tumors are small or anatomically concealed. While tumor-targeted imaging with nanomaterials has shown promise in preclinical models, mechanistic understanding and clinical translation in cancer patients remain limited. Here, in a prospective Phase 2 clinical trial (NCT05576974), we constructed a single-cell spatial atlas of Pegsitacianine, an acid-sensing nanoparticle with activation pH threshold of 5.3, in human squamous carcinoma of the head and neck. Mechanistically, Pegsitacianine preferentially accumulate in immune-in«ltrative severely acidic milieus (iSAM) within tumor stromal regions adjacent to metabolically active cancer cells. Clinically, Pegsitacianine illuminated iSAM regions and achieved ¬ uorescence-guided resection of tumors in 14 of 16 patients with unknown primary cancer, where conventional diagnostic tools failed to locate the tumor. These «ndings establish the mechanistic link between tumor metabolism, immune in«ltration, and nanoparticle delivery, and underscore the clinical value of targeting severe tumor acidosis for cancer detection and therapy.  \nSurgical resection remains as the foundation of cancer care for many solid tumors, provided the tumor can be accurately located. In head and neck squamous cell carcinoma (HNSCC), tumors can metastasize early to cervical lymph nodes while the primary lesion stays undetectable 1. This is particularly common in the oropharynx, where a discontinuous basement membrane and complex lymphoepithelial architecture facilitate early lymphatic spread and hinder direct visualization2-4. Such cases, known as unknown primary cancer (UPC), may present as cervical nodal metastases or be ¬agged by circulating tumor DNA analysis5, 6, yet still lack an accurate identi«cation of primary tumor. Locating primar","cbCaittRO3Yu5Qi8","https://ap.wps.com/l/cbCaittRO3Yu5Qi8","pdf",9233442,21,"English","# Prospective clinical trial overview\n## Study rationale and clinical challenge\n## Nanoparticle design and mechanism\n## Single-cell spatial atlas generation\n## Clinical detection and surgical outcomes\n## Implications for cancer diagnosis and therapy","[{\"question\":\"Why is unknown primary head-and-neck cancer hard to treat surgically?\",\"answer\":\"The primary tumor can remain undetectable even when cervical nodal metastases are present, especially when conventional diagnostics cannot locate the source lesion accurately.\"},{\"question\":\"What is Pegsitacianine and what pH threshold does it target?\",\"answer\":\"Pegsitacianine is an ultra pH-sensitive acid-sensing nanoparticle designed to fluoresce under severe acidic conditions with an activation pH threshold of 5.3.\"},{\"question\":\"How well did Pegsitacianine help detect tumors in the Phase 2 trial?\",\"answer\":\"In the ILLUMINATE Study, fluorescence-guided resection was achieved in 14 of 16 patients with unknown primary cancer when conventional diagnostic tools failed to locate the tumor.\"}]","Homing and Detection of Unknown Primary Head-Neck Cancer by Acid-Sensing Nanoparticles | PDF",1790740980,53]