[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"doc-seo-382134-105":3,"detail-sidebar-cat-0-en-105":81,"doc-detail-382134-en":130},{"code":4,"msg":5,"data":6},0,"ok",{"site_id":7,"language":8,"slug":9,"title":10,"keywords":11,"description":12,"schema_data":13,"social_meta":74,"head_meta":76,"extra_data":78,"updated_unix":80},105,"en","photoactivatable-nanoagonists-chemically-programmed-for-pharmacokinetic-tuning-and-in-situ-cancer-vaccination","Photoactivatable nanoagonists chemically programmed for pharmacokinetic tuning and in situ cancer vaccination","","Immunotherapy can control aggressive and metastatic cancers, yet existing approaches such as immune checkpoint blockade benefit only a limited fraction of patients. A photoactivatable TLR7/8 nanoagonist platform is developed to produce near-infrared light–triggered immunogenic cell death while synchronously releasing a potent immunoadjuvant. The design links a TLR7/8 agonist to biodegradable macromolecular moieties and uses ROS-cleavable linkers plus encapsulated photosensitizers for systemic delivery. In mice and multiple preclinical models, NIR irradiation after intravenous dosing suppresses recurrence and metastasis, remodels the tumor immune landscape, and elicits robust tumor-specific T cell priming.",{"@graph":14,"@context":73},[15,34,56],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/healthcare/","Healthcare",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/photoactivatable-nanoagonists-chemically-programmed-for-pharmacokinetic-tuning-and-in-situ-cancer-vaccination/382134/",4,{"url":32,"name":10,"@type":35,"image":36,"author":41,"headline":10,"publisher":44,"fileFormat":47,"inLanguage":8,"description":12,"dateModified":48,"datePublished":49,"encodingFormat":47,"isAccessibleForFree":50,"interactionStatistic":51},"DigitalDocument",{"url":37,"@type":38,"width":39,"height":40},"https://docshare.wps.com/thumbnails/photoactivatable-nanoagonists-chemically-programmed-for-pharmacokinetic-tuning-and-in-situ-cancer-vaccination/382134.png","ImageObject",300,407,{"name":42,"@type":43},"MrHarris58","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-11-03","2026-09-24",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",10,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"Why are current immunotherapies effective only in a small subset of patients?","Question",{"text":63,"@type":64},"Immune checkpoint blockade responses are limited because tumors often create immunosuppressive microenvironments and many cancers are poorly immunogenic (“cold” tumors), reducing productive immune priming.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"What is the core idea of the photoactivatable nanoagonist platform?",{"text":68,"@type":64},"The platform uses near-infrared photoactivation to induce immunogenic cell death in dying tumor cells while triggering on-demand release of TLR7/8 agonists that stimulate the immune system.",{"name":70,"@type":61,"acceptedAnswer":71},"How does pharmacokinetic tuning improve delivery and treatment outcomes?",{"text":72,"@type":64},"Conjugating a TLR7/8 agonist to biodegradable macromolecular moieties with different molecular weights enables tuning of small-molecule pharmacokinetics and optimized delivery efficiency, which improves NIR-driven therapeutic performance in preclinical models.","https://schema.org",{"og:url":32,"og:type":75,"og:title":10,"og:site_name":45,"og:description":12},"article",{"robots":77,"canonical":32},"index,follow",{"doc_id":79,"site_id":7},382134,1790483980,{"code":4,"msg":82,"data":83},"success",[84,88,92,96,101,106,110,115,120,123,126],{"id":22,"doc_module":4,"doc_module_name":25,"category_name":85,"show_sort_weight":86,"slug":87},"Story & Novel",90,"story-novel",{"id":26,"doc_module":4,"doc_module_name":25,"category_name":89,"show_sort_weight":90,"slug":91},"Literature",80,"literature",{"id":33,"doc_module":4,"doc_module_name":25,"category_name":93,"show_sort_weight":94,"slug":95},"Exam",70,"exam",{"id":97,"doc_module":4,"doc_module_name":25,"category_name":98,"show_sort_weight":99,"slug":100},5,"Comic",60,"comic",{"id":102,"doc_module":4,"doc_module_name":25,"category_name":103,"show_sort_weight":104,"slug":105},6,"Technology",50,"technology",{"id":107,"doc_module":4,"doc_module_name":25,"category_name":29,"show_sort_weight":108,"slug":109},7,40,"healthcare",{"id":111,"doc_module":4,"doc_module_name":25,"category_name":112,"show_sort_weight":113,"slug":114},8,"Research & Report",30,"research-report",{"id":116,"doc_module":4,"doc_module_name":25,"category_name":117,"show_sort_weight":118,"slug":119},9,"Religion & Spirituality",20,"religion-spirituality",{"id":118,"doc_module":4,"doc_module_name":25,"category_name":121,"show_sort_weight":118,"slug":122},"World Cup","world-cup",{"id":55,"doc_module":4,"doc_module_name":25,"category_name":124,"show_sort_weight":55,"slug":125},"Lifestyle","lifestyle",{"id":127,"doc_module":4,"doc_module_name":25,"category_name":128,"show_sort_weight":97,"slug":129},19,"General","general",{"code":4,"msg":82,"data":131},{"doc_id":79,"user_id":132,"nickname":42,"user_avatar":133,"doc_module":4,"category_id":107,"category_name":29,"doc_title":10,"doc_description":12,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":55,"is_deleted":4,"is_public":22,"is_downloadable":22,"audit_status":22,"page_count":139,"language":140,"language_code":8,"site_id":7,"html_lang":8,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":12,"update_tm":144,"read_time":145},687212988360,"https://ap-avatar.wpscdn.com/davatar_276721f389ce27ea32af1340a28f341c","RESEARCH ARTICLE  \nMEDICAL SCIENCES ENGINEERING  \nPhotoactivatable nanoagonists chemically programmed for pharmacokinetic tuning and in situ cancer vaccination  \nJianqin Wana, b, Lulu Rena, Xiaoyan Lia,c, Shasha Hed, Yang Fue, Peirong Xua,c, Fanchao Menga , Shiyun Xiana, Kanyi Pud , and Hangxiang Wanga, b,1 Edited by Darrell J. Irvine, Massachusetts Institute of Technology, Cambridge, MA; received June 17, 2022; accepted January 17, 2023 by Editorial Board Member Rakesh K. Jain  \nImmunotherapy holds great promise for the treatment of aggressive and metastatic cancers; however, currently available immunotherapeutics, such as immune checkpoint blockade, benefit only a small subset of patients. A photoactivatable toll-like receptor 7/8 (TLR7/8) nanoagonist (PNA) system that imparts near-infrared (NIR) light-induced immunogenic cell death (ICD) in dying tumor cells in synchrony with the spontaneous release of a potent immunoadjuvant is developed here. The PNA consists of polymer-derived proimmunoadjuvants ligated via a reactive oxygen species (ROS)-cleavable linker and polymer-derived photosensitizers, which are further encapsulated in amphiphilic matrices for systemic injection. In particular, conjugation of the TLR7/8 agonist resiquimod to biodegradable macromolecular moieties with different molecular weights enabled pharmacokinetic tuning of small-molecule agonists and optimized delivery efficiency in mice. Upon NIR photoirradiation, PNA effectively generated ROS not only to ablate tumors and induce the ICD cascade but also to trigger the on-demand release of TLRagonists. In several preclinical cancer models, intravenous PNA administration followed by NIR tumor irradiation resulted in remarkable tumor regression and suppressed postsurgical tumor recurrence and metastasis. Furthermore, this treatment profoundly shifted the tumor immune landscape to a tumoricidal one, eliciting robust tumor-specific T cell priming in vivo. This work highlights a simple and cost-effective approach to generate in situ cancer vaccines for synergistic photodynamic immunotherapy of metastatic cancers.  \nprodrug design | pharmacokinetic tuning | TLR7/8 agonist | immunotherapy | cancer vaccination  \nCancer immunotherapy has emerged as a powerful therapeutic paradigm that stimulates the patient immune system to achieve durable tumor control and manage metastatic cancer recurrence and treatment escape (1, 2) . Despite the remarkable clinical success of immune checkpoint blockade therapy (e.g., anti-PD-1/PD-L1 and anti-CTLA-4 inhibitors), the responses occur only in a small subset of patients (3, 4) . Growing evidence has suggested that antitumor responses primed by these immunotherapies correlate with the host’s inherent immunological status, and multiple mechanisms of immune resistance exist in tumors (5) . The majority of cancers are poorly immunogenic (so-called “cold” tumors), characterized by the abundant presence of immune suppressors together with a paucity of tumor-infiltrating lymphocytes, making them refractory to conventional immunotherapies (6). Consequently, approaches capable of transforming an immunologically cold tumor microenvironment (TME) into a “hot” one are essential to potentiate cancer immunotherapy (7–9) .  \nToll-like receptor 7/8 (TLR7/8) agonists are involved in innate immune stimulation, activating antigen-presenting cells (APCs) and promoting the subsequent proliferation of T cells (10–12) . Currently, several small-molecule TLR agonists are clinically approved only for topical formulations (13) . Parenteral dosing of these agonists is impeded by systemic distribution and severe immune-related adverse events. Moreover, the pharmacokinetic shortcomings of small molecules, including rapid metabolism and elimination from the systemic circulation and insufficient transport to lymph nodes or tumors, compromise their efficacy (10) . Delivery strategies based on particulate platforms have been developed to address these issues, includ","cbCaiq8XKs2vyAOm","https://ap.wps.com/l/cbCaiq8XKs2vyAOm","pdf",9180829,11,"English","# Significance\n# Background and rationale\n## Limitations of current immunotherapies\n## Cold tumor microenvironment and need for conversion\n# TLR7/8 agonists and delivery challenges\n## Systemic toxicity and pharmacokinetic shortcomings\n## Nanocarrier and activatable nanoparticle strategies\n# Photodynamic therapy and ROS generation\n# Proposed photoactivatable nanoagonist platform\n## Design and mechanism\n## Preclinical efficacy and immune effects","[{\"question\":\"Why are current immunotherapies effective only in a small subset of patients?\",\"answer\":\"Immune checkpoint blockade responses are limited because tumors often create immunosuppressive microenvironments and many cancers are poorly immunogenic (“cold” tumors), reducing productive immune priming.\"},{\"question\":\"What is the core idea of the photoactivatable nanoagonist platform?\",\"answer\":\"The platform uses near-infrared photoactivation to induce immunogenic cell death in dying tumor cells while triggering on-demand release of TLR7/8 agonists that stimulate the immune system.\"},{\"question\":\"How does pharmacokinetic tuning improve delivery and treatment outcomes?\",\"answer\":\"Conjugating a TLR7/8 agonist to biodegradable macromolecular moieties with different molecular weights enables tuning of small-molecule pharmacokinetics and optimized delivery efficiency, which improves NIR-driven therapeutic performance in preclinical models.\"}]","Photoactivatable nanoagonists chemically programmed for pharmacokinetic tuning and in situ cancer vaccination | PDF",1790249222,28]