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arXiv 2025年

作者： Lee, Jingoo Lim, Kyungho Jung, Young-Chul Kim, Byung-Hoon Department of Biomedical Systems Informatics Yonsei University College of Medicine Seoul Korea Republic of Institute of Behavioral Science in Medicine Yonsei University College of Medicine Seoul Korea Republic of Department of Medicine Yonsei University Graduate School Seoul Korea Republic of Department of Psychiatry Yonsei University College of Medicine Seoul Korea Republic of

Recent advances in large language models (LLMs) have accelerated the development of conversational agents capable of generating human-like responses. Since psychiatric assessments typically involve complex conversational interactions between psychiatrists and patients, there is growing interest in developing LLM-based psychiatric assessment conversational agents (PACAs) that aim to simulate the role of psychiatrists in clinical evaluations. However, standardized methods for benchmarking the clinical appropriateness of PACAs' interaction with patients still remain underexplored. Here, we propose PSYCHE, a novel framework designed to enable the 1) clinically relevant, 2) ethically safe, 3) cost-efficient, and 4) quantitative evaluation of PACAs. This is achieved by simulating psychiatric patients based on a multi-faceted psychiatric construct that defines the simulated patients' profiles, histories, and behaviors, which PACAs are expected to assess. We validate the effectiveness of PSYCHE through a study with 10 board-certified psychiatrists, supported by an in-depth analysis of the simulated patient utterances. Copyright © 2025, The Authors. All rights reserved.

关键词： Chatbots

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Decoding innate lymphoid cells and innate-like lymphocytes in asthma: pathways to mechanisms and therapies

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Journal of biomedical Science 2025年第1期32卷 1-17页

作者： Thio, Christina Li-Ping Shao, Jheng-Syuan Luo, Chia-Hui Chang, Ya-Jen Institute of Biomedical Sciences Academia Sinica No. 128 Academia Road Section 2 Nankang Taipei City 115 Taiwan Taiwan International Graduate Program in Molecular Medicine National Yang Ming Chiao Tung University and Academia Sinica Taipei City 115 Taiwan Institute of Translational Medicine and New Drug Development China Medical University Taichung City 404 Taiwan

Asthma is a chronic inflammatory lung disease driven by a complex interplay between innate and adaptive immune components. Among these, innate lymphoid cells (ILCs) and innate-like lymphocytes have emerged as crucial players in shaping the disease phenotype. Within the ILC family, group 2 ILCs (ILC2s), in particular, contribute significantly to type 2 inflammation through their rapid production of cytokines such as IL-5 and IL-13, promoting airway eosinophilia and airway hyperreactivity. On the other hand, innate-like lymphocytes such as invariant natural killer T (iNKT) cells can play either pathogenic or protective roles in asthma, depending on the stimuli and lung microenvironment. Regulatory mechanisms, including cytokine signaling, metabolic and dietary cues, and interactions with other immune cells, play critical roles in modulating their functions. In this review, we highlight current findings on the role of ILCs and innate-like lymphocytes in asthma development and pathogenesis. We also examine the underlying mechanisms regulating their function and their interplay with other immune cells. Finally, we explore current therapies targeting these cells and their effector cytokines for asthma management. © The Author(s) 2025.

关键词： Asthma ILCs Immune regulation Innate-like lymphocytes Therapeutic targets

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Deep imaging of LepR^(+)stromal cells in optically cleared murine bone hemisections

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Bone Research 2025年第1期13卷 104-120页

作者： Yuehan Ni Jiamiao Wu Fengqi Liu Yating Yi Xiangjiao Meng Xiang Gao Luyi Xiao Weiwei Zhou Zexi Chen Peng Chu Dan Xing Ye Yuan Donghui Ding Ge Shen Min Yang Ronjie Wu Ling Wang Luiza Martins Nascentes Melo Sien Lin Xiaoguang Cheng Gang Li Alpaslan Tasdogan Jessalyn M.Ubellacker Hu Zhao Shentong Fang Bo Shen College of Life Sciences Beijing Normal University100875BeijingChina National Institute of Biological Sciences Beijing(NIBS)102206BeijingChina Peking University-Tsinghua University-National Institute of Biological Sciences Joint Graduate Program School of Life SciencesTsinghua University100084BeijingChina School of Biopharmacy China Pharmaceutical University211198NanjingChina Chinese Institute for Brain Research Beijing(CIBR)102206BeijingChina Chinese Academy of Medical Sciences&Peking Union Medical College 100730BeijingChina Peking University-Tsinghua University-National Institute of Biological Sciences Joint Graduate Program Academy for Advanced Interdisciplinary StudiesPeking University100871BeijingChina Arthritis Clinic and Research Center Peking University People’s HospitalPeking University100044BeijingChina Musculoskeletal Research Laboratory Department of Orthopaedics&Traumatology&Li Ka Shing Institute of Health SciencesFaculty of MedicineThe Chinese University of Hong Kong999077ShatinHong Kong SARPR China Department of Radiology Beijing Jishuitan HospitalCapital Medical UniversityNational Center for Orthopaedics100035BeijingChina Department of Dermatology University Hospital Essen&German Cancer ConsortiumPartner SiteEssen45147Germany Department of Molecular Metabolism Harvard T.H.Chan School of Public HealthBostonMA02115USA Tsinghua Institute of Multidisciplinary Biomedical Research Tsinghua University100084BeijingChina

Tissue clearing combined with high-resolution confocal imaging is a cutting-edge approach for dissecting the three-dimensional(3D)architecture of tissues and deciphering cellular spatial interactions under physiological and pathological *** the spatial interaction of leptin receptor-expressing(LepR^(+))stromal cells with other compartments in the bone marrow is crucial for a deeper understanding of the stem cell niche and the skeletal *** this study,we introduce an optimized protocol for the 3D analysis of skeletal tissues,enabling the visualization of hematopoietic and stromal cells,especially LepR+stromal cells,within optically cleared bone *** method preserves the 3D tissue architecture and is extendable to other hematopoietic sites such as calvaria and *** protocol entails tissue fixation,decalcification,and cryosectioning to reveal the marrow *** within approximately 12 days,this process yields highly transparent tissues that maintain genetically encoded or antibody-stained fluorescent *** bone hemisections are compatible with diverse antibody labeling *** microscopy of these transparent samples allows for qualitative and quantitative image analysis using Aivia or Bitplane Imaris software,assessing a spectrum of *** proper storage,the fluorescent signal in the stained and cleared bone hemisections remains intact for at least 2–3 *** protocol is robust,straightforward to implement,and highly reproducible,offering a valuable tool for tissue architecture and cellular interaction studies.

关键词： transparent sections straight

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Two Novel Compounds Isolated from the Marine Fungal Symbiont of Aspergillus unguis Induce Apoptosis and Cell Cycle Arrest in Breast Cancer Cells: In vitro Study

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Journal of Experimental Pharmacology 2025年 17卷 37-50页

作者： Bashari, Muhammad Hasan Agung, Mochamad Untung Kurnia Ariyanto, Eko Fuji Al Muqarrabun, Laode Muhammad Ramadhan Salsabila, Syefira Chahyadi, Agus Rosandy, Andi Rifki Afifah, Ervi Afni, Merry Atmaja, Harold Eka Putri, Tenny Utami, Fitria Subhan, Beginer Syafrizayanti Andriani, Yosie Elfahmi Department of Biomedical Sciences Faculty of Medicine Universitas Padjadjaran West Java Bandung Indonesia Department of Marine Science Faculty of Fisheries and Marine Science Universitas Padjadjaran West Java Bandung Indonesia University Center of Excellence for Nutraceuticals Bioscience and Biotechnology Research Center Bandung Institute of Technology West Java Bandung Indonesia Graduate School of Master Program Faculty of Medicine Universitas Padjadjaran Bandung Indonesia Biomedical Laboratory Faculty of Medicine Universitas Padjadjaran West Java Bandung Indonesia Department of Marine Science and Technology Faculty of Fisheries and Marine Science IPB University West Java Bogor Indonesia Biochemistry Laboratory Department of Chemistry Universitas Andalas West Sumatera Padang Indonesia Institute of Climate Adaptation and Marine Biotechnology Universiti Malaysia Terengganu Kuala Nerus Terengganu Malaysia School of Pharmacy Bandung Institute of Technology West Java Bandung Indonesia

Purpose: A promising feature of marine sponges is the potential anticancer efficacy of their secondary metabolites. The objective of this study was to explore the anticancer activities of compounds from the fungal symbiont of Aaptos suberitoides on breast cancer cells. Methods: In the present research, Aspergillus unguis, an endophytic fungal strain derived from the marine sponge A. suberitoides was successfully isolated and characterized. Subsequently, ethyl acetate extraction and isolation of chemical constituents produced was performed. The structures of the isolated compounds were identified using several spectroscopic methods, ie, UV, NMR, and mass spectrometry. Thereafter, MDA-MB-231, MCF-7 breast cancer cells and HaCat cells were treated with the isolated compounds. Not only viability, apoptosis, and cell cycle analyses were conducted, but also the mRNA expression of MCL1, BCL2L1, AKT1 and CDK2 were evaluated. Results: The extract showed cytotoxic activity in breast cancer cells. Two novel compounds were successfully isolated and identified, ie, Unguisol A (15.1 mg) and Unguisol B (97.9 mg). Both compounds share the same basic skeleton and comprise an aromatic ring which is attached to a sulphur-containing, seven-membered ring via an oxygen atom. This marked the first-time isolation of Unguisol A and Unguisol B from A. unguis, highlighting their novelty. Both compounds induced early apoptosis (p < 0.01) and cell cycle arrest at the S phase (p < 0.05) in MDA-MB-231 cells, but not in HaCat cells. Both compounds suppressed BCL2L1 and AKT1 mRNA expression (p < 0.01). Conclusion: Two novel compounds were isolated from A. unguis. Unguisol A and Unguisol B induced apoptosis in MDA-MB-231 breast cancer cells via BCL2L1 mRNA downregulation, while both compounds induced cell cycle arrest at the S phase through AKT1 mRNA downregulation. © 2025 Bashari et al.

关键词： Aspergillus unguis drug screening assays Porifera triple negative breast neoplasms

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Corrigendum to "Effect of cell imprinting on viability and drug susceptibility of breast cancer cells to doxorubicin" [Acta Biomaterialia, 2020, 113, 119-129] (Acta Biomaterialia (2020) 113 (119–129), (S1742706120303287), (10.1016/***.2020.06.007))

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Acta Biomaterialia 2025年 198卷 571-572页

作者： Shahriyari, Fatemeh Janmaleki, Mohsen Sharifi, Shahriar Hesar, Milad Eyvazi Hoshian, Sasha Taghiabadi, Reza Razaghian, Ahmad Ghadiri, Majid Peirovi, Afshin Mahmoudi, Morteza Nezhad, Amir Sanati Khademhosseini, Ali Division of Engineering in Medicine Department of Medicine Brigham and Women's Hospital Harvard Medical School CambridgeMA United States Division of Health Sciences & Technology Harvard-Massachusetts Institute of Technology Massachusetts Institute of Technology CambridgeMA United States Department of Materials Engineering Faculty of Engineering Imam Khomeini International University Qazvin Iran Biomedical Engineering Graduate Program University of Calgary Canada Precision Health Program and Department of Radiology Michigan State University East LansingMI48824 United States RWTH Aachen University Templergraben 55 Aachen52062 Germany Department of Chemistry and Materials Science Aalto University School of Chemical Engineering Espoo Finland Department of Mechanical Engineering Faculty of Engineering Imam Khomeini International University Qazvin Iran Nano-Biotechnology Department Pasteur Institute of Iran Tehran Iran Departments of Bioengineering Chemical and Biomolecular Engineering and Radiological Sciences Center for Minimally Invasive Therapeutics California NanoSystems Institute University of California – Los Angeles Los AngelesCA United States Terasaki Institute for Biomedical Innovation Los AngelesCA United States

The authors regret to report that the images for panels h (Plain PDMS) and I (MCF7-imprinted PDMS) in Fig. 3 were mistakenly taken from the same dataset, resulting in the omission of the correct image in panel h for the Plain PDMS day 7 image. We sincerely apologize for this error. For an accurate representation, please see the corrected Fig. 3 provided here along with its original figure caption. This does not affect the validity of the statistical analyses or the overall conclusions drawn from the study. © 2025

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Applying an Agile Science Roadmap to Integrate and Evaluate Ethical Frameworks Throughout the Lifecycle and Use of Artificial Intelligence Tools in the Intensive Care Unit

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Critical Care Nursing Clinics of North America 2025年第2期37卷 347-363页

作者： Lindroth, Heidi Sahajwani, Juhi Hudson, Mark Heier, Laura Gonzalez, Andrew A. Bhattacharyya, Anirban Zheng, Zhi Boustani, Malaz Herasevich, Vitaly McGowan, Michelle Barry, Barbara Division of Nursing Research Department of Nursing Mayo Clinic Rochester MN United States Center for Aging Research Regenstrief Institute School of Medicine Indiana University Indianapolis IN United States Center for Health Innovation and Implementation Science School of Medicine Indiana University Indianapolis IN United States Department of Critical Care Medicine Mayo Clinic Jacksonville FL United States School of Psychology and Counselling The Open University Milton Keynes United Kingdom Department of Graduate Nursing Viterbo University La Crosse WI United States Department of Neurosurgery Mayo Clinic Rochester MN United States Center for Health Services Research Regenstrief Institute School of Medicine Indiana University Indianapolis IN United States Surgical Outcomes and Quality Improvement Center Department of Surgery School of Medicine Indiana University Indianapolis IN United States Department of Electrical Engineering University of Notre Dame Notre Dame IN United States Department of Anesthesiology and Perioperative Medicine Mayo Clinic Rochester MN United States Biomedical Ethics Departments of Quantitative Health Sciences and Artificial Intelligence and Informatics Biomedical Ethics Research Program Mayo Clinic Rochester MN United States Kern Center Mayo Clinic Rochester MN United States

This article summarizes existing ethical frameworks for healthcare artificial intelligence (AI) and ambient sensing technology, such as computer vision, and examines their application to improve patient outcomes in the intensive care unit (ICU). Integrating ethical considerations such as privacy, fairness, and autonomy into the lifecycle of an AI tool is necessary to fully harvest AI's potential to deliver safe, high-quality, personalized, and low-cost healthcare services that provide positive experiences for patients, families, and clinicians while improving health outcomes. Drawing from agile science, the article proposes a practical roadmap for clinician and researcher use to identify, integrate, and monitor ethical considerations throughout the lifecycle of an AI tool with the intention to improve patient care. A use case illustrates the application of the agile science-informed roadmap that details the development of a passive digital marker for delirium severity.

关键词： Agile science AI tools Artificial intelligence Computer vision Delirium severity Ethical frameworks for health care AI ICU Passive digital marker

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Unbiased Multiplex Antigen Screening of Cerebrospinal Fluid Detects Microbial and Autoantigenic Epitopes Associated with Multiple Sclerosis

SSRN

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SSRN 2025年

作者： Barton, Nathaniel J. Tran, Khanh Olson, Meagan N. Deshpande, Mugdha Radu, Irina Francis, Nimmy Kurban, Mariana Martin-Puig, Aurelie Wilner, Molly Orszulak, Adrian R. Chigas, Samantha M. Sundstrom, Jonathan Dawes, Pepper Murray, Liam F. Baiby, Marcus Ionete, Carolina Lim, Elaine T. Hemond, Christopher C. Chan, Yingleong Department of Neurology University of Massachusetts Chan Medical School WorcesterMA01605 United States Department of Medicine Division of Innate Immunity University of Massachusetts Chan Medical School WorcesterMA01605 United States NeuroNexus Institute University of Massachusetts Chan Medical School WorcesterMA01605 United States Department of Genomics and Computational Biology University of Massachusetts Chan Medical School WorcesterMA01605 United States Department of Molecular Cell and Cancer Biology University of Massachusetts Chan Medical School WorcesterMA01605 United States Graduate Program in Biochemistry & Molecular Biotechnology Morningside Graduate School of Biomedical Sciences University of Massachusetts Chan Medical School WorcesterMA01605 United States Department of Medicine Division of Cardiovascular Medicine University of Massachusetts Chan Medical School WorcesterMA01605 United States Graduate Program in Immunology and Microbiology Morningside Graduate School of Biomedical Sciences University of Massachusetts Chan Medical School WorcesterMA01605 United States Graduate Program in Neuroscience Morningside Graduate School of Biomedical Sciences University of Massachusetts Chan Medical School WorcesterMA01605 United States

To comprehensively investigate the intrathecal antibody profile of multiple sclerosis (MS), we examined the cerebrospinal fluid of 195 patients (92 MS and 103 non-MS) for antibodies using a multiplex unbiased bacteria peptide library. We first tested against Epstein-Barr nuclear antigen 1 (EBNA1) for epitope sites enriched in MS and found a significant enrichment at position 407-419. We then used the data to perform a high-throughput screen against a library of 129 viruses known to infect humans. We discovered several additional epitopes from viruses such as Hantaan virus, Human Herpesvirus 6A and Human respiratory syncytial virus B associated with MS. Besides viral epitopes, we also screened for potential autoantigens of the central nervous system (CNS). We discovered several autoantigenic epitopes in proteins such as ADRB3, HTR3A and MPO that were significantly enriched for MS. Because of previous associations of Toxoplasma gondii infection with MS, we also performed a Toxoplasma gondii specific analysis and discovered additional epitopes enriched for MS. We further assessed epitope-epitope correlations within the patient samples and found distinct patterns of association between these microbial and autoantigenic epitopes. Finally, we performed machine-learning to determine if these epitopes are predictive for MS and found that the model incorporating all the epitopes could most effectively discriminate between MS and non-MS (ROC-AUC score = 0.91). Our results demonstrate the effectiveness of multiplex unbiased screens to detect the identity of potentially cross-reactive antibodies targeting MS CNS epitopes and they can also be used as effective biomarkers for MS. © 2025, The Authors. All rights reserved.

关键词： Epitopes

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Cryptotanshinone Suppresses the STAT3/BCL-2 Pathway to Provoke Human Bladder Urothelial Carcinoma Cell Death

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Environmental Toxicology 2025年第4期40卷 624-635页

作者： Tung, Min-Che Chang, Ge-Man Dai, Wen-Chyi Hsu, Chen-Hsuan Chang, Hsiang-Chun Yang, Wei-Ting Ho, Yann-Jen Lu, Chien-Hsing Chen, Yi-Hsin Chang, Chia-Che Division of Urology Department of Surgery Tungs' Taichung MetroHarbor Hospital Taichung Taiwan Graduate Institute of Biomedical Sciences National Chung Hsing University Taichung Taiwan Doctoral Program in Biotechnology Industrial Innovation and Management National Chung Hsing University Taichung Taiwan Department of Life Sciences National Chung Hsing University Taichung Taiwan Department of Obstetrics and Gynecology Taichung Veterans General Hospital Taichung Taiwan Doctoral Program in Translational Medicine National Chung Hsing University Taichung Taiwan Department of Nephrology Taichung Tzu Chi Hospital Buddhist Tzu chi Medical Foundation Taichung Taiwan School of Medicine Tzu Chi University Hualein Taiwan Department of Artificial Intelligence and Data Science National Chung Hsing University Taichung Taiwan Master Program in Precision Health Rong Hsing Research Center for Translational Medicine The iEGG and Animal Biotechnology Research Center National Chung Hsing University Taichung Taiwan Department of Medical Laboratory Science and Biotechnology Asia University Taichung Taiwan Department of Medical Research China Medical University Hospital Taichung Taiwan

Bladder cancer is one of the most common human malignancies worldwide. Aberrant activation of signal transducer and activator of transcription 3 (STAT3) is crucial to driving malignant progression and predicting poor prognosis of multiple human cancers, including bladder cancer, making STAT3 a promising target of cancer therapeutics. Cryptotanshinone (CTS) is an anticancer ingredient of Danshen (Salvia miltiorrhiza), a top-graded Chinese medicinal herb. However, whether CTS targets STAT3 to exert its cytotoxic effect on human bladder cancer remains unknown. Herein, we demonstrated that CTS is cytotoxic to multiple human urinary bladder transitional cell carcinoma (TCC) cell lines while sparing normal human urothelial cells. CTS provoked apoptosis-dependent bladder TCC cytotoxicity, as apoptosis blockage by z-VAD-fmk markedly rescued the clonogenicity of CTS-treated cells. Besides, CTS was found to suppress constitutive and interleukin 6-inducible activation of STAT3, evidenced by the downregulation of STAT3 tyrosine 705 phosphorylation and BCL2, a recognized STAT3 transcriptional target. Notably, ectopic expression of a dominant-active STAT3 mutant (STAT3-C) or BCL-2 alleviated CTS-induced apoptosis and clonogenicity inhibition, thus confirming STAT3 blockade as a pivotal mechanism of CTS's cytotoxic action on bladder TCC cells. Lastly, immunoblotting revealed that CTS lowered the levels of active JAK2, an upstream kinase that mediates STAT3 tyrosine 705 phosphorylation. Altogether, we conclude that the blockade of the JAK2/STAT3/BCL-2 antiapoptotic signaling axis is a vital mechanism whereby CTS provokes bladder cancer cytotoxicity. The current evidence implicates CTS's potential to be translated into a bladder cancer therapeutic agent. © 2024 Wiley Periodicals LLC.

关键词： Cell death

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Class-Agnostic Feature-Learning-Based Deep-Learning Model for Robust Melanoma Prediction

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IEEE Journal of biomedical and Health informatics 2025年 PP卷 PP页

作者： Chu, Yuseong Lee, Solam Oh, Byungho Yang, Sejung Yonsei University Department of Biomedical Engineering Wonju Korea Republic of Yonsei University Wonju College of Medicine Department of Dermatology Wonju Korea Republic of Severance Hospital Cutaneous Biology Research Institute Yonsei University College of Medicine Department of Dermatology Seoul Korea Republic of Yonsei University Department of Precision Medicine Wonju College of Medicine Department of Medical Informatics and Biostatistics Graduate School 20 Ilsan-ro Wonju-si Gangwon-do Korea Republic of

Skin lesion images are relatively easy to obtain, but variations in imaging conditions, particularly lesion positioning, can cause inconsistencies in deep learning model activations, impacting diagnostic reliability. In this study, a robust deep-learning model for melanoma prediction was developed using class-agnostic activation maps (CAAMs) for enhanced diagnostic accuracy and reliability by addressing issues related to image variability and transformation robustness. The international skin imaging collaboration (ISIC) 2017 and 2019 datasets, focusing on melanoma and nevus, were used. The performance was evaluated using the area under the receiver operating characteristic curve (AUROC), while Dice scores were used for robustness evaluation. The proposed model achieved an AUROC of 0.954 for ConvNeXt on the ISIC 2019 dataset, with Dice scores of 0.664 and 0.457 for ConvNeXt and ResNet, respectively. For the ISIC 2017 dataset, the proposed model achieved an AUROC of 0.843 for ConvNeXt, with Dice scores of 0.557 and 0.306 for ConvNeXt and ResNet, respectively. The proposed CAAM-based method improved the melanoma prediction and lesion recognition accuracy by ensuring robust and consistent CAAMs. This method is also available publicly at https:-***-wormschu-Class-Agnostic-Feature-Learning-Melanoma-prediction. © 2013 IEEE.

关键词： Contrastive Learning

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Short-Chain Dense Brush Pegylation on Rigid Nanocarriers Overcomes Anti-Peg Antibody Recognition for Immune-Stealth Drug Delivery

SSRN

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SSRN 2025年

作者： Chen, Ting-Yu Chang, Chi-Yuan Wen, Ting-Chun Xu, Li Lin, Yu-Han Peng, Cheng-Liang Yeh, Yi-Qi Chen, Chueh-Hsuan Chuang, Kuo-Hsiang Wu, Si-Han Graduate Institute of Pharmacognosy Taipei Medical University Taipei11031 Taiwan Graduate Institute of Nanomedicine and Medical Engineering Taipei Medical University Taipei11031 Taiwan Department of Isotope Application National Atomic Research Institute Taoyuan Taiwan National Synchrotron Radiation Research Center Hsinchu Science Park Hsinchu30076 Taiwan Research Center for Applied Science Academia Sinica Taiwan PhD Program in Clinical Drug Development of Chinese Herbal Medicine Taipei Medical University Taipei Taiwan International Ph.D. Program in Biomedical Engineering College of Biomedical Engineering Taipei Medical University Taipei11031 Taiwan

The immunogenicity of polyethylene glycol (PEG) remains a critical challenge in nanomedicine, as pre-existing anti-PEG antibodies can compromise therapeutic efficacy through accelerated blood clearance (ABC) and life-threatening hypersensitivity. Here, we address this challenge by engineering the PEG architecture, creating short-chain dense brush PEGylation (PEG500) on rigid mesoporous silica nanoparticles (MSNs). Unlike conventional PEG2000-liposomes, MSN-PEG500 evades antibodies via three synergistic mechanisms: (1) short-chain PEG500 reduces epitope accessibility, (2) high grafting density (4.43 chains/nm2, according to TGA) forms an dense steric shield, and (3) the rigid silica surface prevents PEG burial. ELISA studies demonstrated that, at equivalent nanoparticle concentrations, MSN-PEG500 exhibits a 26-fold reduction in anti-PEG IgG (6.3) binding and a 1000-fold reduction in anti-PEG IgM (AGP3) binding compared to Lipodox (PEG2000), both of which target the PEG backbone. Furthermore, radiolabeled MSN-PEG500 achieved prolonged circulation and 25% tumor accumulation (ID/g) at 24 hours. In strongly immunized mice, doxorubicin-loaded MSN-PEG500 preserved therapeutic efficacy and 100% survival, whereas Lipodox induced fatal hypersensitivity. Mechanistic investigations revealed that complement activation drives PEG2000 immunotoxicity, and pretreatment with the C3 inhibitor compstatin effectively mitigated temperature drops from 10°C to 2°C in immunized hosts. By demonstrating that nanoscale control of polymer conformation dictates immunological fate, this work provides a clinically translatable blueprint for developing immune-evasive nanomedicines. © 2025, The Authors. All rights reserved.

关键词： Silica nanoparticles

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