{"title":"Visualizing Nucleolar Abnormality in Human Cancer Tissues With a Fluorescent RNA Probe for Intraoperative Pathological Diagnosis","authors":"Fangfang Meng, Qing Lyu, Junyi He, Xiuquan He, Miao Cheng, Mingling Luo, Zhaoxin Gao, Junfu Liu, Li Li, Zhiqiang Liu, Jing Zhi Sun, Peng Gao, Kang-Nan Wang, Xiaoqiang Yu","doi":"10.1002/agt2.70435","DOIUrl":"https://doi.org/10.1002/agt2.70435","url":null,"abstract":"<p>Accurately distinguishing malignant from benign tumors within 30 min is an essential yet challenging task for intraoperative pathological diagnosis. However, due to the lack of an efficient fluorophore capable of rapid and precise imaging of nucleoli in human tissues, the clinical diagnostic value of nucleoli remains underexplored, although abnormal nucleolar morphology in cancer cells represents a particularly prominent feature of malignant tumors. Given that nucleoli contain evolutionarily conserved and abundant ribosomal RNA (rRNA), their morphology in various cell types, including normal, benign, and cancerous cells, should be able to be imaged precisely and rapidly by a fluorescent RNA probe with high RNA affinity and tissue permeability. Herein, we developed a fluorescent probe, SDU-CH1, by integrating a pyridinium cation bearing a terminal -NH<sub>3</sub><sup>+</sup> group with a carbazole moiety. Fluorescence spectra and molecular docking calculations revealed that SDU-CH1 exhibited ultra-high affinity for conserved and abundant 18S rRNA through electrostatic interactions, π-π interaction, and hydrogen bonds. Benefiting from exceptional RNA affinity and tissue permeability, SDU-CH1 enabled rapid staining and high-fidelity imaging of nucleoli and cytoplasm in diverse cells within frozen sections of human breast tumor, particularly in ductal epithelial cells where most breast cancer originates. Furthermore, fluorescence imaging of these frozen sections not only allowed clear visualization of nucleolar morphology and abnormality, but also facilitated quantitative assessment of nucleolar area and nucleolar/nuclear area ratio. Importantly, these nucleolar abnormalities and quantitative indicators could be effectively employed to identify malignant tumors, contributing a new method for intraoperative pathological diagnosis.</p>","PeriodicalId":72127,"journal":{"name":"Aggregate (Hoboken, N.J.)","volume":"7 9","pages":""},"PeriodicalIF":13.7,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/agt2.70435","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148942703","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Research Progress of Room-Temperature Phosphorescence Materials Based on Reversible Bonding Interactions","authors":"Dan Li, Jie Yang, Zhen Li","doi":"10.1002/agt2.70437","DOIUrl":"https://doi.org/10.1002/agt2.70437","url":null,"abstract":"<p>Recently, organic room-temperature phosphorescence (RTP) has been greatly developed. The design strategies for common RTP materials are highly dependent on enhancing the intersystem crossing (ISC) efficiency or constructing a rigid ordered microenvironment to suppress non-radiative transitions. Especially in polymer-based RTP systems, this rigid strategy essentially sacrifices the dynamic intelligent response behavior. However, the dynamic covalent bonds and reversible non-covalent bonds can endow RTP systems with the possibility of reversible exchange and reorganization, providing the basis for the materials to exhibit stimulus-responsive functions such as self-healing and shape–memory. Herein, we systematically review the latest progress in the realization of self-healing and shape–memory functions for RTP materials, which are classified according to the types of reversible bonding interactions, including B─O/B─N dynamic bonds, transesterification, metal coordination, hydrogen bond, electrostatic interaction, and host–guest inclusion. In addition, we point out the current issues, challenges, and opportunities of RTP systems based on reversible bonding interactions, and give the development directions in the future.</p>","PeriodicalId":72127,"journal":{"name":"Aggregate (Hoboken, N.J.)","volume":"7 9","pages":""},"PeriodicalIF":13.7,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/agt2.70437","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148942701","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Multilayer Mechanical Transduction Activates Compression-Mode Mechano-Optical Response in Chiral Nematic Liquid Crystal Elastomers","authors":"Ryota Morimoto, Maki Ogata, Kohsuke Matsumoto, Kazuhiro Shimonomura, Osamu Tsutsumi","doi":"10.1002/agt2.70438","DOIUrl":"https://doi.org/10.1002/agt2.70438","url":null,"abstract":"<p>Chiral nematic liquid crystal elastomers (N* LCEs) are photonic elastomers that convert mechanical deformation into changes in selective reflection through modulation of their helical pitch. Although tensile deformation readily induces mechano-optical responses, compressive loading is generally less effectively coupled to pitch modulation in thin elastomer films. Here, we demonstrate multilayer mechanical transduction as a structural strategy for activating optical responses under compression. The multilayer films, consisting of an N* LCE layer sandwiched between compliant polydimethylsiloxane (PDMS) layers, exhibit a pronounced and reversible blueshift of the selective reflection wavelength upon compressive loading, whereas single-layer N* LCE films show negligible optical response under comparable conditions. Spectral measurements, optical imaging, and deformation analysis reveal that the applied compressive stress is converted into PDMS-mediated in-plane expansion, which induces contraction of the adjacent N* LCE layer along the helical axis and consequent shortening of the helical pitch. The reflection wavelengths estimated from geometric deformation agree well with the experimentally measured values, providing quantitative validation of the proposed deformation-mediated transduction model. As a proof-of-concept demonstration, the multilayer films were integrated into a soft robotic gripper to illustrate optical feedback based on material-level pressure transduction without embedded electronic pressure sensors at the sensing interface. These results show that multilayer mechanical architecture can activate compression-mode mechano-optical responses in chiral photonic elastomers.</p>","PeriodicalId":72127,"journal":{"name":"Aggregate (Hoboken, N.J.)","volume":"7 9","pages":""},"PeriodicalIF":13.7,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/agt2.70438","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148942704","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Chirality Fixation of Ag-Based Nanoclusters via Co-Crystallization With Ag–P Complexes: Unlocking Circularly Polarized Luminescence","authors":"Chuanjun Zhou, Xiao Wei, Kaiyang Kuang, Jun Cheng, Sanwen Ni, Jiahao Liu, Wenjun Ma, Hao Li, Shuang Chen, Manzhou Zhu","doi":"10.1002/agt2.70430","DOIUrl":"https://doi.org/10.1002/agt2.70430","url":null,"abstract":"<p>Intrinsically chiral metal nanoclusters capped with achiral ligands have attracted extensive attention for their unique circularly polarized luminescence (CPL) and promising optoelectronic and catalytic applications. However, such nanoclusters generally exist as thermodynamically stable racemic mixtures, and the efficient separation and chiral fixation of single enantiomers remain a long-standing challenge that severely restricts their practical chiroptical applications. Herein, we report a novel co-crystallization strategy to achieve chiral resolution and CPL activation of racemic metal nanoclusters. A new racemic nanocluster [AuAg<sub>28</sub>(H<sub>2</sub>NC<sub>6</sub>H<sub>4</sub>S)<sub>12</sub>(PPh<sub>3</sub>)<sub>12</sub>Cl<sub>6</sub>]<sup>3+</sup> was synthesized, and homochiral single crystals were successfully obtained by co-crystallization with achiral Ag(PPh<sub>3</sub>)<sub>3</sub>Cl complexes. The introduced Ag–P complexes provide abundant intermolecular interaction sites, while the phenyl groups induce strong T-shaped π–π stacking forces that rigidly fix the nanocluster into a single chiral conformation. Benefiting from this supramolecular confinement effect, the homochiral crystals exhibit prominent CPL performance. Furthermore, this strategy can be extended to isostructural Ag<sub>29</sub> nanoclusters; the corresponding co-crystals also display near-infrared CPL, while core-metal substitution achieves ∼50 nm emission redshift. This work reveals an atomic-scale chiral induction mechanism based on achiral co-crystallization, offering a facile strategy for the design and regulation of high-performance chiral luminescent nanomaterials.</p>","PeriodicalId":72127,"journal":{"name":"Aggregate (Hoboken, N.J.)","volume":"7 9","pages":""},"PeriodicalIF":13.7,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/agt2.70430","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148942624","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Mechanically Robust and Wear-Resistant 3D-Printable Polyurethane Elastomers Through UPy-Based Supramolecular Reinforcement","authors":"Xingxing Yang, Desheng Liu, Xiarong Zhang, Changcheng Bai, Xin Xu, Zongbin Sun, Jia Yao, Yixian Wang, Qiong Su, Xin Jia, Xiaolong Wang","doi":"10.1002/agt2.70429","DOIUrl":"https://doi.org/10.1002/agt2.70429","url":null,"abstract":"<p>The pursuit of adequate mechanical robustness, particularly exceptional toughness and abrasion resistance, in polyurethane elastomers is a prerequisite for any application, yet the development of such a functionally structural elastomer presents a prodigious challenge. Herein, a photocurable elastomer is engineered through an innovative supramolecular engineering strategy that leverages dynamic quadruple hydrogen bonding (QHB), achieved by incorporating 2-amino-5-(2-hydroxyethyl)-6methylpyrimidin-4-ol (UPy) moieties into the polyurethane backbone. The robust microphase-separated architectures within elastomers arise from UPy dimer self-assembly via strong QHB, and systematically increasing the UPy content promotes hard-phase aggregation, enhances H-bonding density, and improves thermal stability. The resulting optimal elastomer demonstrates exceptional mechanical performance. The dynamic nature of the supramolecular network further endows the elastomer with exceptional abrasion resistance, facilitating energy dissipation and load bearing. To demonstrate this concept, we fabricated an artificial polyurethane meniscus model from the photosensitive prepolymer via vat photopolymerization 3D printing, achieving wear-resistant lubrication. This research advances the effectiveness of a strategic supramolecular design approach for creating high-performance elastomers that integrate multifunctionality with structural complexity.</p>","PeriodicalId":72127,"journal":{"name":"Aggregate (Hoboken, N.J.)","volume":"7 9","pages":""},"PeriodicalIF":13.7,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/agt2.70429","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148942622","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Wenkai Zhang, Xueke Yan, Xiepeng Deng, Chen Cui, Dalu Xie, Ben Zhong Tang, Huifang Su
{"title":"Achieving Hierarchical Selective Ablation and Remodeling “Cold” Tumors via a Dual-Organelle-Targeted AIE Nanoplatform: Synergizing Ferroptosis, ICD, and cGAS–STING Activation","authors":"Wenkai Zhang, Xueke Yan, Xiepeng Deng, Chen Cui, Dalu Xie, Ben Zhong Tang, Huifang Su","doi":"10.1002/agt2.70426","DOIUrl":"https://doi.org/10.1002/agt2.70426","url":null,"abstract":"<p>Immunotherapy has created new opportunities for treating triple-negative breast cancer (TNBC), but its benefit is often limited by an immunosuppressive tumor microenvironment. Here, we report BMFL, a folate receptor-targeted liposomal nanoplatform that co-delivers a near-infrared aggregation-induced emission luminogens (AIEgens), BITT, and the STING agonist MSA-2 for dual-organelle-directed photoimmunotherapy. BMFL enables fluorescence discrimination of lipid droplets and lysosomes and, under phototherapy, couples lipid droplet peroxidation-driven ferroptosis with lysosome-associated immunogenic cell death (ICD). Ferroptosis-associated mitochondrial stress promotes endogenous mtDNA leakage, which cooperates with the delivered exogenous MSA-2 to drive upstream activation of the STING pathway; meanwhile, immunostimulatory signals released during ICD further synergize with the STING-mediated inflammatory microenvironment to achieve downstream amplification of adaptive antitumor immunity. In a bilateral tumor model, BMFL-mediated therapy not only eradicates primary tumors but also elicits systemic antitumor immunity and suppresses distal tumor growth. In this study, BMFL functions as a dual-organelle-targeting nanoplatform that enhances therapeutic efficacy by coupling ferroptosis with ICD through the cGAS–STING pathway, offering a potential strategy for treating poorly immunogenic breast tumors.</p>","PeriodicalId":72127,"journal":{"name":"Aggregate (Hoboken, N.J.)","volume":"7 9","pages":""},"PeriodicalIF":13.7,"publicationDate":"2026-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/agt2.70426","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148860041","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Dual-Acceptor Engineered Multimodal Phototheranostic NIR-II AIEgens for Orthotopic Breast Cancer Treatment","authors":"Miaomiao Kang, Yu Pei, Zengming Yang, Yinzhen Pan, Zhijun Zhang, Xue Li, Dong Wang, Ben Zhong Tang","doi":"10.1002/agt2.70427","DOIUrl":"https://doi.org/10.1002/agt2.70427","url":null,"abstract":"<p>“One‑for‑all” phototheranostics has emerged as a promising alternative to conventional cancer therapies. Aggregation‑induced emission luminogens (AIEgens) are exemplary templates for constructing such versatile systems. However, developing robust NIR‑II (1000–1700 nm)-emitting “one‑for‑all” phototheranostic AIEgens remains challenging, due to the drastically lowered reactive oxygen species (ROS) generation capability and strong intermolecular π-π stacking in the NIR‑II range. To address this, an ingenious dual‑acceptor strategy was proposed. It leverages the steric hindrance between two moderate‑strength acceptors to create a twisted dual‑acceptor configuration, which not only circumvents the detrimental effects caused by large planar strong acceptors, such as π–π stacking-induced emission quenching and excited-state energy loss, but also favors AIE nature. Moreover, moderate‑strength acceptors are readily functionalized, facilitating the introduction of substituents that enhance ROS performance. Through combining a strong donor, an optimized AIE small molecule, TTBI, was identified, which exhibits desirable NIR‑II emission, excellent type I ROS production, and a high photothermal conversion after formulation into nanoparticles (NPs). Coupled with outstanding stability and biocompatibility, TTBI NPs demonstrated exceptional 808 nm‑excitable NIR-II fluorescence–photoacoustic–photothermal trimodal imaging and synergistic photodynamic–photothermal therapy in mouse orthotopic breast cancer models. This work provides new insights for creating superior NIR‑II multimodal phototheranostic agents.</p>","PeriodicalId":72127,"journal":{"name":"Aggregate (Hoboken, N.J.)","volume":"7 9","pages":""},"PeriodicalIF":13.7,"publicationDate":"2026-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/agt2.70427","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148860043","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
He Zhu, Cong Wang, Shiqi Guo, Jialin Zhu, Mao Chen, Mei Liu, Weihua Ding, Shiqian Shen, Leilei Li, Jiahao Zhong, Yunlong Zhao, Gang Wang, Dong Yang
{"title":"Multifunctional Transition Metal Dichalcogenide-Based Electronic Skin for AI-Enhanced Multimodal Human–Machine Interaction and Robotic Control","authors":"He Zhu, Cong Wang, Shiqi Guo, Jialin Zhu, Mao Chen, Mei Liu, Weihua Ding, Shiqian Shen, Leilei Li, Jiahao Zhong, Yunlong Zhao, Gang Wang, Dong Yang","doi":"10.1002/agt2.70428","DOIUrl":"https://doi.org/10.1002/agt2.70428","url":null,"abstract":"<p>Wearable electronic skin (e-skin) provides a transformative approach to human–machine interaction by seamlessly integrating physiological sensing and environmental perception with robotic control. Here, we present a multifunctional e-skin platform in which two-dimensional transition-metal dichalcogenide MoSe<sub>2</sub> supports NO<sub>2</sub> sensing, photodetection, and FET operation, whereas Au-based structures enable surface electromyography (sEMG) acquisition and temperature sensing. Representative device performance included NO<sub>2</sub> sensing over 0.5–10 ppm, a photodetector on/off ratio exceeding 100, and a temperature sensitivity of 2.2 Ω °C<sup>−</sup><sup>1</sup>. By integrating sEMG-based muscle activity recognition with voice commands and a large language model-assisted task planning module, we establish a multimodal human–machine interaction framework that combines high-level semantic instructions with low-level sEMG-derived motor skills for intuitive robotic task execution. The proposed multimodal human–machine interaction framework enables robotic tasks, including object retrieval, object manipulation, and quadruped locomotion, by combining voice commands with sEMG-based control, thereby facilitating the intuitive translation of human intentions into robotic actions. Using a six-gesture sEMG dataset collected from one participant over 10 acquisition rounds, the e-skin system was evaluated using 10-fold round-wise cross-validation, with eight rounds used for training, one randomly assigned round for validation, and one round for testing in each fold. The GRU classifier achieved a mean fold accuracy of 97.88% ± 1.50% (population standard deviation), a pooled balanced accuracy of 97.91%, a Cohen's κ of 0.9747, and a macro-F1 score of 97.92%, and was successfully integrated into real-time robotic control applications. This work establishes a scalable foundation for next-generation assistive robotics, teleoperation, and industrial automation, where seamless human-robot collaboration is critical.</p>","PeriodicalId":72127,"journal":{"name":"Aggregate (Hoboken, N.J.)","volume":"7 9","pages":""},"PeriodicalIF":13.7,"publicationDate":"2026-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/agt2.70428","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148860042","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chenyue Xu, Ying Ji, Xingqun Pu, Wenjun Peng, Long Jiang, Jingjun Wu, Qian Zhao, Zizheng Fang, Tao Xie
{"title":"3D Printing of Bio-Based Elastomers With High Toughness","authors":"Chenyue Xu, Ying Ji, Xingqun Pu, Wenjun Peng, Long Jiang, Jingjun Wu, Qian Zhao, Zizheng Fang, Tao Xie","doi":"10.1002/agt2.70423","DOIUrl":"https://doi.org/10.1002/agt2.70423","url":null,"abstract":"<p>The rapid development of 3D printing, combined with the urgent need to address fossil resource depletion and environmental pollution, has spurred strong interest in utilizing bio-based feedstocks for additive manufacturing of polymers. Despite extensive efforts, a key bottleneck remains in how to achieve superior mechanical properties at a high bio-content. Fundamentally, the difficulty lies in how to construct the appropriate aggregation states key to the mechanical properties under the constraints of bio-based 3D printing. Here, we report our successful attempt in this direction. At a high bio-content of 76%, our printed elastomer exhibits tensile strength (37.1 MPa) and toughness (156.9 MJ m<sup>−3</sup>) far exceeding any known 3D-printed bio-based elastomers and even commercial petroleum-based elastomers. The material design is further extended to produce 3D foams with a tensile strength of 1.2 MPa at a low density of 0.26 g cm<sup>−3</sup>. This ability to 3D print mechanically robust architectured foams opens up new structure design opportunities to maximize material utilization efficiency. Our findings underscore the potential for sustainable manufacturing of high-performance 3D printing.</p>","PeriodicalId":72127,"journal":{"name":"Aggregate (Hoboken, N.J.)","volume":"7 8","pages":""},"PeriodicalIF":13.7,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/agt2.70423","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148783559","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Surface Hydrophobicity Dictates Environment-dependent Colloidal Stability of Organic Phototheranostic Nanoparticles","authors":"Fan Xiao, Hongyan Li, Mengying Wang, Zixiang Wei, Yulin Zhu, Wenkang Zhang, Leilei Tian","doi":"10.1002/agt2.70425","DOIUrl":"https://doi.org/10.1002/agt2.70425","url":null,"abstract":"<p>Organic phototheranostic nanoparticles (OPNPs) have gained significant attention in bioimaging, sensing, and therapy owing to their tunable optical properties and multifunctional theranostic capabilities. Composed of amphiphilic polymeric carriers (APCs) and hydrophobic chromophores, their colloidal stability in aqueous environments is critical for preserving optical performance and ensuring in vivo efficacy. Herein, we systematically compare the colloidal stability of OPNPs in physiological saline versus the bloodstream, uncovering distinct environment-dependent behaviors that are primarily governed by OPNP surface hydrophobicity, which is tunable via the intrinsic hydrophobicity of the APCs. Specifically, OPNPs prepared with higher hydrophobic carriers aggregate in saline but remain stable in the bloodstream, whereas those with less hydrophobic carriers show the opposite trend. Mechanistically, this environment-dependent stability arises from differential interfacial interactions: surface hydrophobicity modulates ion-induced poly(ethylene glycol) dehydration and aggregation in saline, while governing protein-mediated stability regulation in serum. Overall, our findings establish surface hydrophobicity as a pivotal regulator of OPNP colloidal stability and provide a rational design principle for engineering OPNPs tailored to specific biomedical scenarios (e.g., in vitro detection vs. in vivo therapy).</p>","PeriodicalId":72127,"journal":{"name":"Aggregate (Hoboken, N.J.)","volume":"7 8","pages":""},"PeriodicalIF":13.7,"publicationDate":"2026-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/agt2.70425","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148783859","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}