{"title":"Propiolates-Based Selective Labeling and Affinity Capture Enables High-Fidelity Transcriptome-Wide Profiling of A-to-I RNA Editing.","authors":"Jian-Feng Qin, Tong-Meng Yan, Chen Huang, Ying-Wei Wang, Yu Pan, Hao Shi, Pei-Jie Zhu, Xiao Yang, Zhi-Hong Jiang","doi":"10.1021/acs.bioconjchem.5c00300","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.5c00300","url":null,"abstract":"<p><p>Adenosine-to-inosine (A-to-I) RNA editing is a critical post-transcriptional modification that regulates various biological processes and has been implicated in neurological diseases, cancer, and autoimmune diseases. However, current methods for detecting A-to-I sites, including inosine chemical erasing and acrylonitrile-derivative labeling, suffer from compromised sensitivity and specificity due to two critical limitations: cross-reactivity with pseudouridine and suboptimal enrichment efficiency. Here, we introduce a novel chemical labeling strategy using propiolates as selective inosine-binding agents, coupled with biotin-streptavidin enrichment, enabling precise transcriptome-wide profiling of A-to-I editing sites. Through screening a range of propiolates and optimizing the reaction conditions, we demonstrated that <i>tert</i>-butyl propiolate functions as a highly selective probe, achieving 6-fold higher specificity for I compared to pseudouridine (Ψ) in RNA editing detection. This scaffold represents the first application of propiolates in RNA editing detection. Subsequent RT-qPCR analysis revealed that the optimized protocol achieved a 55-fold enrichment efficiency of inosine-containing RNAs through copper-free click chemistry conjugation and streptavidin magnetic bead pulldown. Compared to acrylonitrile-derivative labeling methods, this protocol represents a 3.7-fold improvement in enrichment efficiency. Applied to human cellular RNA, this method robustly identified A-to-I editing sites with enhanced accuracy and coverage. By reducing pseudouridine cross-reactivity and enabling efficient RNA enrichment, our strategy provides a universal platform for studying RNA editing dynamics in development, disease, and therapeutic contexts, thereby opening new avenues for epitranscriptomic biomarker discovery. This work advances the molecular toolbox for epitranscriptomics, offering broad utility in dissecting the functional roles of A-to-I editing in health and pathology.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145297963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mackenzie L Smith, Sarah Sirajuddin, Adriana N Santiago-Miranda, Richard R Rustandi, Jacob H Waldman, Mikhail Reibarkh, Joseph P Smith, Patrick M McHugh
{"title":"Elucidating the Critical Attributes of Sodium Triacetoxyborohydride to Tune Glycoconjugation via Reductive Amination.","authors":"Mackenzie L Smith, Sarah Sirajuddin, Adriana N Santiago-Miranda, Richard R Rustandi, Jacob H Waldman, Mikhail Reibarkh, Joseph P Smith, Patrick M McHugh","doi":"10.1021/acs.bioconjchem.5c00377","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.5c00377","url":null,"abstract":"<p><p>Pneumococcal conjugate vaccines (PCVs) have effectively enhanced immunogenicity by conjugating a carrier protein to a purified capsular polysaccharide. The degree of conjugation influences the effective size of the final conjugate, and control of this reaction is critical in developing a robust process. Sodium triacetoxyborohydride (STAB) is a common reducing agent used to perform reductive aminations to provide a means for conjugation and can be utilized as an <i>in situ</i> preparation in the PCV conjugation process. Robust analytical methods for characterizing STAB were not previously available. Herein, we develop methods to rapidly assess STAB for both activity and composition using quantitative NMR methodologies and apply these learnings to improve our understanding of the bioconjugation process. It was determined that decreasing the reaction temperature to synthesize STAB resulted in a more active reducing reagent enriched with sodium diacetoxyborohydride (SDAB). Conjugation reactions performed with a model polysaccharide and carrier protein found that an increased SDAB content led to larger conjugation sizes. Moreover, we established a correlation between the conjugate size and SDAB concentration by charging the reaction with varying molar equivalents of SDAB. Through this work, a deeper understanding of the critical attributes of STAB was developed using diverse analytical methods, and these learnings can be applied to develop a more appropriate control strategy for producing glycoconjugate therapeutics.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145297903","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yimei Zhang, Liqun Wei, Xiaole Yin, Yiliang Xie, Hang Gao, Bing Zhang, Zhihuan Zhao, Weihong Zhao, Min Xu
{"title":"Double-Responsive Metallic Magnetic Nanoparticles Based on Tumor Microenvironment \"Leverage\" Rebalancing for Triple Collaborative Cancer Therapy.","authors":"Yimei Zhang, Liqun Wei, Xiaole Yin, Yiliang Xie, Hang Gao, Bing Zhang, Zhihuan Zhao, Weihong Zhao, Min Xu","doi":"10.1021/acs.bioconjchem.5c00475","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.5c00475","url":null,"abstract":"<p><p>Targeted perturbation of redox balance through concurrent elevation of reactive oxygen species (ROS) production and glutathione (GSH) depletion has emerged as a therapeutic paradigm for triggering tumor cell apoptosis. Nevertheless, the conventional single-agent system demonstrates limited therapeutic efficacy due to insufficient oxidative stress amplification within tumor cells. Herein, we designed pH- and GSH double-responsive metallic magnetic Ag-NH<sub>2</sub>-CoFe<sub>2</sub>O<sub>4</sub>@C@DOX nanoparticles (ANFCD NPs), which disrupted the redox balance within the tumor microenvironment (TME) to achieve synergistic chemodynamic therapy (CDT), photothermal therapy (PTT), and chemotherapy (CT) effects. In the acidic TME, ANFCD NPs functioned as both a Fenton catalyst and GSH depletor through the reversible redox property of Fe (II/III) and Co (I/II), inducing oxidative stress and exerting a \"leverage\" rebalancing to potentiate CDT. Additionally, ANFCD NPs showed high photothermal conversion efficiency, enhancing PTT efficacy via magnetic targeting-driven tumor accumulation. Meanwhile, they could also responsively release DOX to achieve CT. More importantly, the hyperthermia generated by ANFCD NPs not only effectively eradicated tumor cells but also boosted the CDT effect and promoted DOX release, ultimately achieving the aim of combined therapy. Therefore, such a nanomaterial is a promising therapeutic agent for disrupting redox homeostasis to augment multimodal collaborative therapy, which might show further applications in nanomedical science.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145290343","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Mitochondria-Targeting Antimicrobial Peptide (AMP) Regulating N6-Methyladenosine (m6A) Modification to Promote Colon Cancer Ferroptosis.","authors":"Chenyu Li, Shuai Li, Linlin Lv, Yanwei Chen, Shilei Yang, Yan Lu, Deshi Dong","doi":"10.1021/acs.bioconjchem.5c00459","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.5c00459","url":null,"abstract":"<p><p>Colon cancer (COAD) is one of the common malignant tumors in the gastrointestinal tract; it is urgent to deeply study the mechanism of COAD and develop new therapeutic agents, which will provide new hope for improving the therapeutic efficacy and prolonging the survival of patients. Mitochondria are crucial organelles that play an important role in COAD, participating in cellular energy and material metabolism and playing a key role in the regulation of cell death, making mitochondria a potential target for COAD therapy. In this study, we designed an antimicrobial peptide (AMP) that can target tumor cells and act on mitochondria. The AMP is taken up by tumor cells and can achieve colocalization with mitochondria, reducing the mitochondrial membrane potential levels in tumor cells and inducing ferroptosis. The AMP affects N6-methyladenosine (m6A) methylation modification in cells and participates in the regulation of ferroptosis. During in vivo experiments on COAD, the AMP demonstrated a strong ability to inhibit tumor growth and good biosafety. Unlike peptide-drug conjugates that rely on toxin release, the synthetic AMP exerts direct targeted activity with improved biosafety and efficiency. The AMP effectively suppresses the development of COAD, providing a new reference method for the treatment of COAD.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145285068","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xianhao Wei, Jiarui Qiao, Wenjing Wei, Meng Liu, Yan Wang, Tingyan Jiang, Junhe Ou, Luwen Zhang, Maolin Pang
{"title":"A HCOF-Based Drug Delivery System for Cancer Therapy via Intracellular Click Chemistry.","authors":"Xianhao Wei, Jiarui Qiao, Wenjing Wei, Meng Liu, Yan Wang, Tingyan Jiang, Junhe Ou, Luwen Zhang, Maolin Pang","doi":"10.1021/acs.bioconjchem.5c00285","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.5c00285","url":null,"abstract":"<p><p>Click reactions exhibit remarkable selectivity within biological systems, making them powerful and useful tools for synthesizing various novel anticancer drugs in biomedical fields. Utilizing the overexpressed enzyme in a tumor microenvironment to trigger click reactions between nontoxic or low-toxicity precursors provides an effective solution to the high toxicity of conventional chemotherapeutic agents. However, small-molecule drugs tend to undergo rapid metabolism within biological environments; therefore, an effective drug delivery system was needed. In this study, a hollow covalent organic framework (HCOF) was introduced, prodrug molecules were loaded, and finally, an anticancer drug was formed via the click reaction with the help of nitroreductase (NTR). Both in vitro and in vivo studies confirmed the excellent antitumor efficacy of the resulting therapeutic platform. This work further expands the biomedical applications of HCOF via click chemistry.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145273137","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jung Me Hwang, Young-Chul Shin, Enkhzul Amasanaa, Nayoung Kim, Seok-Pyo Hong, Insung S Choi, Young Hye Kim, Hyun-A Seong, Kyungjae Myung, Zee-Won Lee, Kyung-Bok Lee
{"title":"Live-Cell Imaging of the Binding between a Chemical Drug and Its Target Proteins Based on Intracellular Redistribution of the Target Proteins.","authors":"Jung Me Hwang, Young-Chul Shin, Enkhzul Amasanaa, Nayoung Kim, Seok-Pyo Hong, Insung S Choi, Young Hye Kim, Hyun-A Seong, Kyungjae Myung, Zee-Won Lee, Kyung-Bok Lee","doi":"10.1021/acs.bioconjchem.5c00308","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.5c00308","url":null,"abstract":"<p><p>In modern pharmacology, obtaining an in-depth understanding of the interaction of chemical drugs with their target proteins is essential for drug discovery and the advancement of precision medicine. However, detecting these drug-protein interactions in living cells remains challenging owing to the lack of reliable methodologies. The current study presents a robust strategy involving the redistribution of target proteins in cells and applying a cotranslocation-based cellular assay for monitoring drug-target interactions in living cells. This technique utilizes an enhanced green fluorescent protein (EGFP)-tagged drug target protein that is translocated from the cytoplasm to the plasma membrane when exposed to a biotin-conjugated drug and phorbol 12-myristate 13-acetate (PMA). This movement is facilitated by the membrane-translocation properties of the C1A-mRFP-streptavidin fusion protein, which anchors the biotinylated small-molecule drug and facilitates the spatial redistribution of its target proteins. This system provides a dynamic tool for the real-time observations of drug-protein binding events within cellular environments.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145248991","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mei Li, Jinglan Wang, Qinan Li, Xiaoxia Zhang, Luxi Yang, Yumin Li, Wenting He, Tao Liu
{"title":"Indocyanine Green-Labeled Antibody-NOTCH2 as a New Fluorescent Molecular Imaging Probe for Gastric Cancer.","authors":"Mei Li, Jinglan Wang, Qinan Li, Xiaoxia Zhang, Luxi Yang, Yumin Li, Wenting He, Tao Liu","doi":"10.1021/acs.bioconjchem.5c00465","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.5c00465","url":null,"abstract":"<p><p>Gastric cancer is a malignant tumor that seriously threatens human health. Its high mortality is mainly due to delayed diagnosis, which makes early detection important for improving patient prognosis. Near-infrared (NIR) fluorescence imaging, with its high signal-to-noise ratio and good sensitivity, has been widely applied in biomedical research and clinical diagnosis. NOTCH2 is often overexpressed in gastric cancer and may serve as a useful target for diagnosis and treatment. In this study, we constructed a NOTCH2-targeted single-chain variable fragment (scFv) conjugated with indocyanine green (ICG) and evaluated its application in gastric cancer imaging in vitro and in vivo. The ICG-scFv probe showed similar photophysical properties to free ICG and was specifically taken up by MKN45 gastric cancer cells. In NIR imaging, ICG-scFv selectively accumulated in tumor tissue, achieved tumor-specific imaging, and maintained fluorescence signals for a longer time, which was further confirmed by colocalization analysis. These results indicate that the targeted fluorescent probe ICG-scFv may have potential value in the diagnosis and treatment of gastric cancer.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145248984","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kaiyuan Guo, , , Dinglingge Cao, , , Lucia P. Marchese-Thomas, , and , Yizhou Dong*,
{"title":"Antibody Engineering for Receptor-Mediated Transcytosis Across the Blood–Brain Barrier","authors":"Kaiyuan Guo, , , Dinglingge Cao, , , Lucia P. Marchese-Thomas, , and , Yizhou Dong*, ","doi":"10.1021/acs.bioconjchem.5c00379","DOIUrl":"10.1021/acs.bioconjchem.5c00379","url":null,"abstract":"<p >Efficient delivery of therapeutic antibodies into the central nervous system (CNS) remains severely limited by the restrictive nature of the blood–brain barrier (BBB). Receptor-mediated transcytosis (RMT) has emerged as a promising strategy to enhance antibody transport across the BBB. In this Viewpoint, we highlight recent advances in RMT-based antibody delivery, focusing specifically on three representative BBB receptors: transferrin receptor (TfR), insulin receptor (InsR), and neonatal Fc receptor (FcRn). By comparing antibody engineering strategies that target these receptors, we summarize current progress, discuss critical limitations, and suggest directions for advancing CNS-targeted therapeutic antibodies. This Viewpoint provides valuable insights for selecting appropriate RMT targets and optimizing antibody-based therapies for CNS diseases.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":"36 10","pages":"2109–2115"},"PeriodicalIF":3.9,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145197408","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hanyue Ma, , , Lysanne D. A. N. de Muynck, , , Ruben D. Houvast, , , Savanne Beekman, , , Amber Piet, , , Taryn L. March, , , Lukas J. A. C. Hawinkels, , , J. Sven D. Mieog, , , Alexander L. Vahrmeijer, , and , Yann Seimbille*,
{"title":"Revolutionizing Solid Tumor Surgery with Fibroblast Activation Protein (FAP)-Targeted Imaging Probes for a Fluorescence-Guided Surgery of Pancreatic Cancer","authors":"Hanyue Ma, , , Lysanne D. A. N. de Muynck, , , Ruben D. Houvast, , , Savanne Beekman, , , Amber Piet, , , Taryn L. March, , , Lukas J. A. C. Hawinkels, , , J. Sven D. Mieog, , , Alexander L. Vahrmeijer, , and , Yann Seimbille*, ","doi":"10.1021/acs.bioconjchem.5c00218","DOIUrl":"10.1021/acs.bioconjchem.5c00218","url":null,"abstract":"<p >The development of fluorescent probes that target the tumor stroma to help surgeons detect and remove malignant lesions using near-infrared fluorescence (NIRF)-guided surgery is advancing rapidly. Such advancements show promise for a range of malignancies, expanding the eligibility of patients for surgical intervention and offering improved surgical outcomes. Fibroblast activation protein (FAP), expressed by cancer-associated fibroblasts (CAFs), is highly upregulated within the tumor stroma of nearly all solid tumors. It is a promising tumor target for NIRF-guided surgery, especially in solid tumors with dense tumor stroma, such as pancreatic cancer. In this study, we aimed to develop FAP-targeting fluorescent probes with enhanced pharmacokinetics for the NIRF-guided surgery of pancreatic cancer. Three novel FAP-targeted probes (eFAPs) based on a (4-quinolinoyl)-glycyl-2-cyanopyrrolidine (QCP) structure equipped with the NIRF dye IRDye800CW were designed and synthesized. All of the probes displayed excellent inhibition potency and selectivity to FAP. The probes consistently exhibited strong inhibition and specific uptake in FAP-expressing U87 glioblastoma cells. In in vivo optical imaging studies, eFAP-24 showed a tumor-to-background ratio (TBR) of 3.1 ± 0.6 at 24 h postinjection, enabling the clear delineation of tumors using the clinical Quest Spectrum NIRF imaging system. A strong fluorescence signal in the tumor and a negligible uptake in nontarget tissues were confirmed by biodistribution analyses. The successful development and validation of FAP-targeting fluorescent probes, especially eFAP-24, offers promising prospects for enhancing the visualization of FAP-rich stromal compartments improving surgical outcomes through NIRF-guided surgery, particularly in solid tumors with dense stroma such as pancreatic cancer.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":"36 10","pages":"2145–2157"},"PeriodicalIF":3.9,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145204996","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xiaochen Yang, , , Dan Tang, , , E Pang, , , Qiuyi Yang, , , Shaojing Zhao, , , Jianing Yi*, , , Minhuan Lan*, , and , Jie Zeng*,
{"title":"Kaempferol–Iron Assembled Nanoparticles for Synergistic Photothermal and Chemodynamic Therapy of Breast Cancer","authors":"Xiaochen Yang, , , Dan Tang, , , E Pang, , , Qiuyi Yang, , , Shaojing Zhao, , , Jianing Yi*, , , Minhuan Lan*, , and , Jie Zeng*, ","doi":"10.1021/acs.bioconjchem.5c00391","DOIUrl":"10.1021/acs.bioconjchem.5c00391","url":null,"abstract":"<p >Photothermal and chemodynamic therapies (PTT and CDT) have gained traction as viable adjunct anti-cancer treatments. However, they remain restricted by the low efficiency of photothermal conversion and the inefficiency of the Fenton reaction. Kaempferol (Kae), a naturally occurring bioactive flavonoid, can induce apoptotic signaling pathways by reducing the expression or activity of many proteins involved in the initiation and execution phases of apoptosis. In this study, we fabricated Kae–iron-assembled nanoparticles (Kae-Fe NPs) for synergistic PTT and CDT in breast cancer treatment. Under 808 nm laser irradiation, the Kae-Fe NPs not only facilitated the photon-to-heat energy conversion for PTT but also enhanced CDT by improving the efficiency of the Fenton reaction. Additionally, treatment with Kae-Fe NPs induced the release of immunostimulatory signals from breast cancer cells, leading to the migration of HMGB1 and CRT protein expression, and the release of ATP into the extracellular space, thereby triggering immunogenic cell death (ICD) and macrophage polarization toward the M1 type. The implications of these results are that Kae-Fe NPs have a dual effect: reprogramming macrophage phenotypes and inducing ICD. Furthermore, this study lays a firm foundation for utilizing Kae-Fe NPs in breast cancer management.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":"36 10","pages":"2287–2297"},"PeriodicalIF":3.9,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145190421","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}