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Multimodal activity-affinity assay of ADAM-10 extracellular vesicles in untreated plasma reveals metastatic stage of colorectal cancer 未经治疗的血浆中ADAM-10细胞外囊泡的多模态活性亲和力测定显示结直肠癌的转移阶段
IF 10.5 1区 生物学 Q1 BIOPHYSICS Pub Date : 2026-06-15 Epub Date: 2026-02-11 DOI: 10.1016/j.bios.2026.118517
Tiger Haoran Shi , John Alex Sinclair , Youwen Zhang , Xuemin Lu , Sonu Kumar , Xin Lu , Satyajyoti Senapati , Hsueh-Chia Chang
Metalloproteinases (MPs) such as a-disintegrin and metalloproteinase-10 (ADAM-10) are key drivers of extracellular matrix remodeling during tumor progression, yet MP-based liquid biopsy tests have not reached clinical utility. Here, we show that active ADAM-10 is selectively enriched on the surface of circulating extracellular vesicles (EVs) in the plasma of colorectal cancer patients. Our findings further suggest ADAM-10+ EVs are locally enriched in dense pre-metastatic tumor extracellular matrices and subsequently accumulate in blood post-metastasis. To capture these unique signatures of disease progression, an ADAM-10 activity assay is integrated with a novel size-sensitive Immuno-Janus Particle affinity assay for characterizing ADAM-10+ EVs in untreated plasma. In a 43-patient colorectal cancer cohort, this multimodal platform distinguishes healthy, pre-metastatic, and metastatic states with 95% overall accuracy. When combined with lipidomics as a third modality, the platform correctly determines 97.4% cancer stage accuracy, with only one misclassification. This study establishes a multimodal EV-based activity/affinity assay as a robust framework for liquid biopsy, providing accurate cancer staging, improved prognostics, and offering a potential platform for pan-disease diagnostics.
金属蛋白酶(MPs)如a-崩解素和金属蛋白酶-10 (ADAM-10)是肿瘤进展过程中细胞外基质重塑的关键驱动因素,但基于mp的液体活检试验尚未达到临床应用。本研究表明,结直肠癌患者血浆中活性ADAM-10选择性富集在循环细胞外囊泡(EVs)表面。我们的研究结果进一步表明,ADAM-10+ ev在密集的转移前肿瘤细胞外基质中局部富集,随后在转移后的血液中积累。为了捕捉疾病进展的这些独特特征,我们将ADAM-10活性测定与一种新型的尺寸敏感免疫- janus颗粒亲和力测定相结合,用于表征未经处理血浆中的ADAM-10+ ev。在43例结直肠癌患者队列中,该多模式平台区分健康、转移前和转移状态的总体准确率为95%。当与脂质组学结合作为第三种模式时,该平台正确地确定了97.4%的癌症分期准确性,只有一个错误分类。本研究建立了一种基于ev的多模式活性/亲和力测定方法,作为液体活检的一个强大框架,提供准确的癌症分期,改善预后,并为泛疾病诊断提供潜在的平台。
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引用次数: 0
Intraocular-microenvironment responsive fluorescent hydrogels in rhegmatogenous retinal detachment repair 眼内微环境反应性荧光水凝胶在孔源性视网膜脱离修复中的应用
IF 5.6 2区 医学 Q1 BIOPHYSICS Pub Date : 2026-06-01 Epub Date: 2026-01-28 DOI: 10.1016/j.colsurfb.2026.115473
Yuzheng Zhou , Chunli Ma , Yibin Sun , Yuan Wu , Tongfeng Han , Yongqiang Xue , Guotai Li , Qihui Zhou , Zhaodong Du
Rhegmatogenous retinal detachment (RRD) is a severe eye condition that can threaten vision without proper treatment. The primary treatment for RRD is vitrectomy, however, the postoperative requirement for a prone position, coupled with unsatisfactory retinal reattachment rates, presents a significant clinical challenge. Recent advancements in technology and material engineering have led to the development of specific biomaterials serving as retinal patches that can seal retinal breaks. Whereas, existing materials still face limitations including the need for specialized implantation instruments and complex surgical operations for certain materials, inadequate conformability to the eyeball due to relatively high material rigidity that impairs sealing performance, and poor biocompatibility. To overcome these difficulties, herein we introduce a novel fluorescent hydrogel composed of 4-arm-PEG-Mal and 4-arm-PEG-SH as a retinal sealant. This innovative material undergoes rapid gelation in response to the weakly alkaline intraocular environment following injury, enabling effective sealing of retinal breaks and the surrounding area. Furthermore, the hydrogel's inherent fluorescent property provides enhanced intraoperative visibility. Evaluated in a rabbit model of retinal detachment, the hydrogel demonstrated efficient therapeutic treatment in promoting RRD repair, while offering significant visual and surgical advantages. In conclusion, the retinal break-sealing hydrogel developed in this work presents a promising new strategy for the treatment of RRD, with considerable potential for clinical translation.
孔源性视网膜脱离(RRD)是一种严重的眼病,如果不进行适当的治疗,可能会威胁视力。RRD的主要治疗方法是玻璃体切除术,然而,术后对俯位的要求,加上不理想的视网膜再附着率,提出了一个重大的临床挑战。最近技术和材料工程的进步导致了特定生物材料的发展,作为视网膜贴片,可以密封视网膜断裂。然而,现有的材料仍然面临着局限性,包括需要专门的植入器械和某些材料复杂的外科手术,由于相对较高的材料刚性而影响密封性能,与眼球的一致性不足,以及生物相容性差。为了克服这些困难,本文介绍了一种由4臂peg - mal和4臂peg - sh组成的新型荧光水凝胶作为视网膜密封剂。这种创新材料在损伤后的弱碱性眼内环境中快速凝胶化,使视网膜断裂和周围区域有效密封。此外,水凝胶固有的荧光特性增强了术中可见性。在兔视网膜脱离模型中评估,水凝胶在促进RRD修复方面表现出有效的治疗效果,同时具有显着的视觉和手术优势。总之,在这项工作中开发的视网膜破裂密封水凝胶为RRD的治疗提供了一个有希望的新策略,具有相当大的临床转化潜力。
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引用次数: 0
A wearable system enabling acute stress monitoring and closed-loop mitigation through transcutaneous median nerve stimulation 一种可穿戴系统,通过经皮正中神经刺激实现急性应激监测和闭环缓解
IF 10.5 1区 生物学 Q1 BIOPHYSICS Pub Date : 2026-06-01 Epub Date: 2026-01-29 DOI: 10.1016/j.bios.2026.118461
Farhan N. Rahman , Prabhkirat S. Bindra , Afra Nawar , H. Trask Crane , Jesus Antonio Sanchez-Perez , John A. Berkebile , Onur Selim Kilic , Chuoqi Chen , Vikram Abbaraju , Christopher J. Nichols , Jacob M. Cook , Samer Mabrouk , Asim H. Gazi , Jin-Oh Hahn , Omer T. Inan
<div><h3>Background</h3><div>Acute stress, in moderation, helps to prepare the body to overcome mental and physical challenges. However, excessive bouts of acute stress can be detrimental to the cardiovascular system and are a risk factor for cardiovascular disease and sudden cardiac death. Transcutaneous median nerve stimulation (tMNS) is a promising therapy for the mitigation of acute stress through peripheral neuromodulation, but the optimal delivery of tMNS for stress mitigation may require continuous monitoring of acute stress events for targeted delivery.</div></div><div><h3>Objective</h3><div>The purpose of this study was to develop a wearable system capable of continuous closed-loop acute stress monitoring and mitigation through non-invasive cardiovascular sensing and tMNS respectively.</div></div><div><h3>Methods</h3><div>A wearable wrist-worn device capable of sensing three channels of photoplethysmogram (PPG) and tri-axial accelerometry was designed. Pulse rate (PR) and PPG amplitude (PPGamp) were extracted from the acquired green PPG signal, while tMNS was delivered at varying intensities by custom-designed analog circuitry onboard the device. A companion app was used to wirelessly set stimulation levels by communicating with the device's microcontroller using Bluetooth low energy. The device was validated against bench-top sensors in a study with 19 healthy participants involving acute mental and physical stressors as well as tMNS. Repeated-measures correlation and Bland-Altman analyses were performed to compare PR extracted from 9904 5-s windows of PPG from the device and heart rate (HR) extracted beat-by-beat from bench-top electrocardiogram (ECG) and averaged across the same windows. Statistical tests were also performed to analyze differences in mean PR and PPGamp from baseline metrics across the acute stress and tMNS protocol.</div></div><div><h3>Results</h3><div>PR extracted from our device correlated (r = 0.871, p < 0.001) and agreed (mean difference: 0.51 bpm, 95 % limits of agreement: 6.58 bpm, 5.57 bpm) strongly with HR extracted from bench-top ECG. We found decreases in mean PPGamp from baseline during stressors, while application of tMNS alongside stressors increased PPGamp back to baseline levels, and continued delivery of tMNS post-stressor further increased PPGamp to a significant difference from baseline. Significant reductions in PR as compared to baseline post-physical stressor also mirrored these findings, suggesting that our wearable device can track elevations in acute stress through cardiovascular monitoring while also mitigating the effects of acute stress through tMNS.</div></div><div><h3>Conclusion</h3><div>Our device is the first wearable, to our knowledge, to enable continuous monitoring of acute stress through cardiovascular sensing and feature extraction while mitigating acute stress through peripheral neuromodulation. Future work should test the device in ambulatory settings and investigate potential
适度的急性压力有助于身体为克服心理和生理挑战做好准备。然而,过度的急性应激对心血管系统有害,是心血管疾病和心源性猝死的危险因素。经皮正中神经刺激(tMNS)是一种通过周围神经调节缓解急性应激的有前景的治疗方法,但tMNS缓解应激的最佳递送可能需要持续监测急性应激事件以靶向递送。目的研制一种可穿戴系统,通过无创心血管传感和tMNS分别对急性应激进行连续闭环监测和缓解。方法设计一种具有三通道光容积脉搏波和三轴加速度测量传感功能的可穿戴式腕带装置。从采集的绿色PPG信号中提取脉冲速率(PR)和PPG幅度(PPGamp),同时通过设备上定制的模拟电路以不同强度传递tMNS。一个配套的应用程序通过低功耗蓝牙与设备的微控制器通信来无线设置刺激水平。在一项针对19名健康参与者的研究中,该设备通过台式传感器进行了验证,参与者包括急性精神和身体压力以及tMNS。通过重复测量相关性和Bland-Altman分析,比较从设备中提取的9904个5-s窗口的PPG和从台架心电图(ECG)中提取的逐拍心率(HR),并在相同窗口中取平均值。还进行了统计检验,以分析急性应激和tMNS方案中平均PR和PPGamp与基线指标的差异。结果从我们的设备提取的spr与台式心电图提取的HR具有很强的相关性(r = 0.871,p <; 0.001),且一致性(平均差值:0.51 bpm, 95 %一致性限:6.58 bpm, 5.57 bpm)。我们发现,在应激刺激期间,平均PPGamp较基线下降,而在应激刺激的同时使用tMNS使PPGamp回升至基线水平,并且继续使用tMNS后应激刺激进一步使PPGamp与基线有显著差异。与基线后应激源相比,PR的显著降低也反映了这些发现,这表明我们的可穿戴设备可以通过心血管监测跟踪急性应激的升高,同时也可以通过tMNS减轻急性应激的影响。据我们所知,我们的设备是第一个可穿戴设备,可以通过心血管传感和特征提取来连续监测急性应激,同时通过周围神经调节来减轻急性应激。未来的工作应该在门诊环境中测试该设备,并研究临床用例(如焦虑或创伤障碍)的潜在应用。
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引用次数: 0
A dual-mode electrochemiluminescence/SERS biosensor for B-type natriuretic peptide based on a T7–CRISPR/Cas13a cascade and a CsPbBr3@PDA@Au perovskite interface 基于T7-CRISPR /Cas13a级联和CsPbBr3@PDA@Au钙钛矿界面的b型利钠肽双模电化学发光/SERS生物传感器
IF 10.5 1区 生物学 Q1 BIOPHYSICS Pub Date : 2026-06-01 Epub Date: 2026-02-06 DOI: 10.1016/j.bios.2026.118484
Yang Li , Haozhen Ren , Runze Wu , Jiahui Wang , Yuanxun Gong , Qianli Tang , Xianjiu Liao , Kai Zhang , Longjian Huang , Jihua Wei
B-type natriuretic peptide (BNP) is an important biomarker for cardiovascular diseases, motivating sensitive and robust quantification in complex matrices. Here we report a single-electrode, anti-correlated dual-mode electrochemiluminescence/surface-enhanced Raman scattering (ECL/SERS) biosensor that couples split-aptamer recognition with a solution-phase T7 transcription–CRISPR/Cas13a cascade and an interfacial toehold-mediated strand-displacement “probe-stripping” transduction on a CsPbBr3@PDA@Au-modified glassy carbon electrode. BNP binding releases an active T7 template to generate trigger RNA, which activates Cas13a collateral cleavage to produce initiator strands for interfacial unlocking. The interface reaction removes ferrocene/Raman co-labeled probes, synchronizing ECL turn-on with SERS turn-off and enabling ratiometric quantification (R = IECL/ISERS) to suppress common-mode variability. The sensor provides BNP determination over 0–106 aM with log-linear single-mode calibrations and a continuous ratiometric response. Selectivity was validated against multiple interferents and the structurally related peptide NT-proBNP at the same concentration (106 aM), showing negligible ratiometric change relative to BNP. Serum-sample evaluation and stability tests further support feasibility in complex matrices. This work establishes a cascade-to-interface ratiometric strategy for robust protein biosensing.
b型利钠肽(BNP)是一种重要的心血管疾病生物标志物,在复杂的基质中具有敏感性和鲁棒性。在这里,我们报道了一种单电极,抗相关双模式电化学发光/表面增强拉曼散射(ECL/SERS)生物传感器,该传感器将分裂适体识别与溶液相T7转录- crispr /Cas13a级联和界面支点介导的链位移“探针剥离”转导结合在CsPbBr3@PDA@ au修饰的玻璃碳电极上。BNP结合释放活性T7模板生成触发RNA,触发Cas13a侧切产生启动链用于界面解锁。界面反应去除二茂铁/拉曼共标记探针,同步ECL开启和SERS关闭,并使比率量化(R = IECL/ISERS)能够抑制共模变异性。该传感器提供0-106 aM的BNP测定,具有对数线性单模校准和连续比例响应。在相同浓度(106 aM)下,对多种干扰素和结构相关肽NT-proBNP的选择性被验证,相对于BNP显示出可忽略不计的比率变化。血清样品评估和稳定性测试进一步支持在复杂基质中的可行性。这项工作建立了一个级联到界面的比例策略稳健的蛋白质生物传感。
{"title":"A dual-mode electrochemiluminescence/SERS biosensor for B-type natriuretic peptide based on a T7–CRISPR/Cas13a cascade and a CsPbBr3@PDA@Au perovskite interface","authors":"Yang Li ,&nbsp;Haozhen Ren ,&nbsp;Runze Wu ,&nbsp;Jiahui Wang ,&nbsp;Yuanxun Gong ,&nbsp;Qianli Tang ,&nbsp;Xianjiu Liao ,&nbsp;Kai Zhang ,&nbsp;Longjian Huang ,&nbsp;Jihua Wei","doi":"10.1016/j.bios.2026.118484","DOIUrl":"10.1016/j.bios.2026.118484","url":null,"abstract":"<div><div>B-type natriuretic peptide (BNP) is an important biomarker for cardiovascular diseases, motivating sensitive and robust quantification in complex matrices. Here we report a single-electrode, anti-correlated dual-mode electrochemiluminescence/surface-enhanced Raman scattering (ECL/SERS) biosensor that couples split-aptamer recognition with a solution-phase T7 transcription–CRISPR/Cas13a cascade and an interfacial toehold-mediated strand-displacement “probe-stripping” transduction on a CsPbBr<sub>3</sub>@PDA@Au-modified glassy carbon electrode. BNP binding releases an active T7 template to generate trigger RNA, which activates Cas13a collateral cleavage to produce initiator strands for interfacial unlocking. The interface reaction removes ferrocene/Raman co-labeled probes, synchronizing ECL turn-on with SERS turn-off and enabling ratiometric quantification (R = I<sub>ECL</sub>/I<sub>SERS</sub>) to suppress common-mode variability. The sensor provides BNP determination over 0–10<sup>6</sup> aM with log-linear single-mode calibrations and a continuous ratiometric response. Selectivity was validated against multiple interferents and the structurally related peptide NT-proBNP at the same concentration (10<sup>6</sup> aM), showing negligible ratiometric change relative to BNP. Serum-sample evaluation and stability tests further support feasibility in complex matrices. This work establishes a cascade-to-interface ratiometric strategy for robust protein biosensing.</div></div>","PeriodicalId":259,"journal":{"name":"Biosensors and Bioelectronics","volume":"301 ","pages":"Article 118484"},"PeriodicalIF":10.5,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146147347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Exploration of sub-cellular responses for the evaluation of the laser mediated tumor ablation via Raman spectroscopic platform using green synthesized gold nanostars 利用绿色合成金纳米星在拉曼光谱平台上探索激光介导肿瘤消融的亚细胞反应
IF 5.6 2区 医学 Q1 BIOPHYSICS Pub Date : 2026-06-01 Epub Date: 2026-01-25 DOI: 10.1016/j.colsurfb.2026.115472
BS Unnikrishnan , GU Preethi , PT Sujai , Kaustabh Kumar Maiti , TT Sreelekha
Anisotropic gold nanoparticles with surface plasmon resonance (SPR) can generate heat upon exposure to laser light, which can then be utilised for photothermal therapy (PTT) in cancer treatment. In this study, we report the use of doxorubicin (DOX)-loaded immunomodulatory polysaccharide (PST001) coated anisotropic gold nanostars (AuNS@PST) as a theranostic carrier for photothermal-chemotherapy. AuNS@PST were prepared by green synthesis followed by doxorubicin encapsulation. The synthesized particles were characterized using UV–vis spectroscopy, DLS, FTIR and TEM. The heat dissipation of these nanoparticles was monitored in aqueous phantoms using 635 nm laser sources, which indicated the thermal rise from ambient temperature. The in vitro cytotoxicity analysis of AuNS@PST was done using the MTT assay in A549 cells. Significantly lower IC50 value was observed for cells treated with DOX-loaded PST AuNSs when compared to DOX-alone treated cells. Similarly, DOX-loaded AuNS@PST had efficient photothermal-induced apoptosis exerted by the laser-irradiated nanoparticles. Changes in protein degradation and DNA fragmentation at the subcellular levels were observed in the Raman spectrum. Although supplementary perspectives are required in the proper investigation of laser-mediated cell death in cancer tissues, the current study discloses the emerging methodology to track apoptotic events in cancer tissues using the Raman scattering platform, even at the sub-cellular level.
具有表面等离子体共振(SPR)的各向异性金纳米粒子可以在激光照射下产生热量,然后可以用于光热治疗(PTT)癌症治疗。在这项研究中,我们报道了使用负载阿霉素(DOX)的免疫调节多糖(PST001)包被各向异性金纳米星(AuNS@PST)作为光热化疗的治疗载体。AuNS@PST为绿色合成工艺,经阿霉素包封制备。采用紫外可见光谱、DLS、FTIR和TEM对合成的颗粒进行了表征。利用635 nm激光源对纳米颗粒在水相模型中的散热进行了监测,结果表明纳米颗粒的热升高与环境温度有关。采用MTT法对A549细胞进行AuNS@PST体外细胞毒性分析。与单独处理dox的细胞相比,负载dox的PST AuNSs处理细胞的IC50值显着降低。同样,负载dox的AuNS@PST具有有效的光热诱导的凋亡,由激光照射的纳米颗粒施加。在拉曼光谱中观察到亚细胞水平上蛋白质降解和DNA断裂的变化。虽然在癌症组织中激光介导的细胞死亡的适当研究中需要补充的观点,但目前的研究揭示了使用拉曼散射平台甚至在亚细胞水平上跟踪癌症组织中凋亡事件的新兴方法。
{"title":"Exploration of sub-cellular responses for the evaluation of the laser mediated tumor ablation via Raman spectroscopic platform using green synthesized gold nanostars","authors":"BS Unnikrishnan ,&nbsp;GU Preethi ,&nbsp;PT Sujai ,&nbsp;Kaustabh Kumar Maiti ,&nbsp;TT Sreelekha","doi":"10.1016/j.colsurfb.2026.115472","DOIUrl":"10.1016/j.colsurfb.2026.115472","url":null,"abstract":"<div><div>Anisotropic gold nanoparticles with surface plasmon resonance (SPR) can generate heat upon exposure to laser light, which can then be utilised for photothermal therapy (PTT) in cancer treatment. In this study, we report the use of doxorubicin (DOX)-loaded immunomodulatory polysaccharide (PST001) coated anisotropic gold nanostars (AuNS@PST) as a theranostic carrier for photothermal-chemotherapy. AuNS@PST were prepared by green synthesis followed by doxorubicin encapsulation. The synthesized particles were characterized using UV–vis spectroscopy, DLS, FTIR and TEM. The heat dissipation of these nanoparticles was monitored in aqueous phantoms using 635 nm laser sources, which indicated the thermal rise from ambient temperature. The <em>in vitro</em> cytotoxicity analysis of AuNS@PST was done using the MTT assay in A549 cells. Significantly lower IC<sub>50</sub> value was observed for cells treated with DOX-loaded PST AuNSs when compared to DOX-alone treated cells. Similarly, DOX-loaded AuNS@PST had efficient photothermal-induced apoptosis exerted by the laser-irradiated nanoparticles. Changes in protein degradation and DNA fragmentation at the subcellular levels were observed in the Raman spectrum. Although supplementary perspectives are required in the proper investigation of laser-mediated cell death in cancer tissues, the current study discloses the emerging methodology to track apoptotic events in cancer tissues using the Raman scattering platform, even at the sub-cellular level.</div></div>","PeriodicalId":279,"journal":{"name":"Colloids and Surfaces B: Biointerfaces","volume":"262 ","pages":"Article 115472"},"PeriodicalIF":5.6,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146049234","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Copper-infused 13–93 bioactive glass inhibiting postoperative osteosarcoma recurrence and enhancing bone regeneration 铜注入13-93生物活性玻璃抑制术后骨肉瘤复发及促进骨再生
IF 5.6 2区 医学 Q1 BIOPHYSICS Pub Date : 2026-06-01 Epub Date: 2026-01-27 DOI: 10.1016/j.colsurfb.2026.115475
Hao Gong , Zhengfeng Lu , Suming Wei , Yongjun Rui
Osteosarcoma (OS)-induced bone abnormalities present a considerable clinical challenge due to elevated chances of recurrence and compromised repair, which significantly jeopardize patient survival. Contemporary bioactive glasses (BGs), notwithstanding their osteogenic potential, exhibit restricted anticancer efficacy. Therefore, It is essential to enhance the tumor-killing efficacy of BGs for usage as a filler in tumor-induced bone defects. Here, a copper (Cu)-doped 13–93BG (13–93BG-Cu) was synthesized and subsequently combined with chitosan to form the 13–93BG-Cu system. The rapid release of Cu ions (Cu2 +) during the initial stages of this system enhances the killing of tumor cells by cuproptosis, as intracellular Cu2+ accumulation triggers the oxidative stress response within mitochondria, hence achieving anti-OS therapy. Subsequently, the sustained low-level release of Cu2+ and bioactive ions collaboratively influences the activation and function of macrophage and stem cells, promoting bone defect healing. This study introduces a dual-action BG that simultaneously neutralizes the acidic tumor microenvironment and promotes cuproptosis, effectively preventing recurrence while facilitating bone healing via Cu2+ gradient release.
骨肉瘤(OS)诱导的骨异常由于其复发和修复的机会增加而面临着相当大的临床挑战,这严重危及患者的生存。当代生物活性玻璃(BGs)尽管具有成骨潜能,但抗癌功效有限。因此,提高BGs作为肿瘤诱导的骨缺损填充物的杀伤效果是非常必要的。本文合成了一种铜(Cu)掺杂的13-93BG (13-93BG -Cu),并与壳聚糖结合形成13-93BG -Cu体系。在该系统的初始阶段,Cu离子(Cu2 +)的快速释放增强了cuproposis对肿瘤细胞的杀伤作用,因为细胞内Cu2+的积累触发了线粒体内的氧化应激反应,从而实现了抗os治疗。随后,Cu2+和生物活性离子的持续低水平释放协同影响巨噬细胞和干细胞的激活和功能,促进骨缺损愈合。本研究引入了一种双作用的BG,它可以同时中和酸性肿瘤微环境和促进铜增生,有效防止复发,同时通过Cu2+梯度释放促进骨愈合。
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引用次数: 0
Biomimetic red blood cell membrane–coated cerium metal–organic framework for multi-target synergistic therapy of Alzheimer’s disease 仿生红细胞膜包覆金属铈-有机框架多靶点协同治疗阿尔茨海默病
IF 5.6 2区 医学 Q1 BIOPHYSICS Pub Date : 2026-06-01 Epub Date: 2026-01-23 DOI: 10.1016/j.colsurfb.2026.115464
Fengmei Yang , Yutong Chen , Yujiao Yan , Ruixin Zhao , Liran Deng , Die Tian , Meng Xie
Pathological events in Alzheimer’s disease (AD) typically involve β-amyloid (Aβ) plaque deposition, metal ion dysregulation, oxidative stress elevation, and chronic neuroinflammation, making single-target therapies unsatisfactory. Here, we first report a biomimetic nanoplatform based on red blood cell membrane–coated cerium metal–organic frameworks (Ce-MOF-RBC) that enables multi-target synergistic intervention against AD. The Ce-MOF core exhibits potent antioxidant activity, efficiently scavenging reactive oxygen species (ROS) and restoring mitochondrial membrane potential, while its carboxylate ligands chelate Cu2 + with high efficiency (49.26 %) to inhibit Cu2+-induced Aβ fibrillation and disassemble preformed fibrils. Ce-MOF-RBC further modulates microglial phenotype, enhancing Aβ phagocytosis and reducing neuroinflammation. Importantly, RBC membrane functionalization markedly improves biological performance by prolonging systemic circulation, enhancing blood–brain barrier (BBB) penetration, and leveraging its intrinsic affinity for Aβ peptides to enrich Aβ. In vivo fluorescence imaging and brain cryosections showed that Ce-MOF-RBC achieved robust accumulation in the cortex and hippocampus, with brain fluorescence intensities 27.33-fold higher than free DiD. In the C. elegans AD model, Ce-MOF-RBC reduced Aβ plaque fluorescence by 32.54 %, lowered ROS levels by 45.72 %, improved chemotaxis performance (chemotaxis index increased from 34.24 % to 68.34 %), and delayed paralysis onset from 10 h to 15 h, demonstrating significant rescue of cognitive and motor deficits. In summary, these findings highlight the first demonstration of a small-sized, biomimetic Ce-MOF-RBC nanoplatform that integrates antioxidant, metal-chelating, anti-aggregation, and immunomodulatory functions, offering a promising strategy for comprehensive AD therapy.
阿尔茨海默病(AD)的病理事件通常包括β-淀粉样蛋白(Aβ)斑块沉积、金属离子失调、氧化应激升高和慢性神经炎症,这使得单靶点治疗不理想。在这里,我们首次报道了一种基于红细胞膜涂层铈金属有机框架(Ce-MOF-RBC)的仿生纳米平台,该平台可以实现对AD的多靶点协同干预。Ce-MOF核心具有强大的抗氧化活性,可有效清除活性氧(ROS)并恢复线粒体膜电位,而其羧酸配体可高效(49.26 %)螯合Cu2 +,抑制Cu2+诱导的Aβ纤颤和分解预形成的原纤维。Ce-MOF-RBC进一步调节小胶质细胞表型,增强Aβ吞噬和减少神经炎症。重要的是,红细胞膜功能化通过延长体循环,增强血脑屏障(BBB)渗透,并利用其对Aβ肽的内在亲和力来丰富Aβ,显著提高了生物学性能。体内荧光成像和脑冷冻切片显示,Ce-MOF-RBC在皮质和海马区有强大的积累,脑荧光强度比游离DiD高27.33倍。在秀丽隐杆线虫AD模型中,Ce-MOF-RBC降低了Aβ斑块荧光32.54 %,降低了ROS水平45.72 %,改善了趋化性表现(趋化性指数从34.24 %增加到68.34 %),并将麻痹发作时间从10 h推迟到15 h,显示出对认知和运动缺陷的显著缓解。总之,这些发现强调了一个小尺寸、仿生Ce-MOF-RBC纳米平台的首次展示,该平台集抗氧化、金属螯合、抗聚集和免疫调节功能于一体,为全面治疗阿尔茨海默病提供了一个有希望的策略。
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引用次数: 0
Corrigendum to "Fabrication of PCL/PVP Electrospun Fibers loaded with Trans-anethole for Bone Regeneration in vitro" [Colloids Surf. B Biointerfaces 171 (2018) 698-706]. “PCL/PVP静电纺丝纤维的制备装载反式甲醚用于体外骨再生”的更正[Colloids Surf]。[j].中国生物医学工程学报,2018,33(5):559 - 567。
IF 5.6 2区 医学 Q1 BIOPHYSICS Pub Date : 2026-06-01 Epub Date: 2026-02-10 DOI: 10.1016/j.colsurfb.2026.115511
R PranavKumar Shadamarshan, Harini Balaji, Harsha Shrihari Rao, K Balagangadharan, S Viji Chandran, N Selvamurugan
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引用次数: 0
Genetically encoded biosensor of apoptosis and necrosis reveals the dynamics and biphasic cytotoxicity by Anti-EGFR CAR-T cells 基因编码的细胞凋亡和坏死生物传感器揭示了抗egfr CAR-T细胞的动态和双相细胞毒性。
IF 10.5 1区 生物学 Q1 BIOPHYSICS Pub Date : 2026-06-01 Epub Date: 2026-02-06 DOI: 10.1016/j.bios.2026.118471
Aijaz Ahmad Rather , Aman Munirpasha Halikar , Ritika Sachdeva , Shivanshu Kumar Tiwari , T.R. Santhoshkumar
Precise and quantitative evaluation of CAR-T cell-induced cytotoxicity by resolving distinct cell death phenotypes in live cells remains a critical unmet need in the development of immunotherapies. Discriminating between apoptosis and necrosis induced by CAR-T therapy at single-cell resolution is essential for elucidating cytotoxic mechanisms and predicting therapeutic outcomes. Yet, most live cell assays lack the spatiotemporal sensitivity to do so. Here, we present a genetically encoded dual-biosensor system that concurrently monitors caspase-3/7 activation and mitochondrial integrity, enabling the real-time distinction between apoptosis and necrosis. The platform combines a FRET-based caspase sensor (RealCas3) and a mitochondria-targeted DsRed reporter (MitoDsRed) that exhibits compatibility with both microscopy imaging and flow cytometry. We applied this platform to functionally profile anti-EGFR CAR-T cells and uncover a biphasic cytotoxicity pattern, marked by early caspase-3/7 induced apoptosis, followed by a delayed necrosis. Notably, the system enables the time-resolved detection of secondary necrosis, a delayed immunogenic death phenotype that is often misclassified in conventional assays. The developed platform offered a robust and scalable approach for real-time functional phenotyping of immune effector responses, addressing a key gap in evaluating cell death mechanisms during immunotherapy development. By enabling the time-resolved quantification of tumor cell demise along with the mode of death, this dual-sensor system established a mechanistic framework for evaluation and rational design of safer and more effective next-generation immunotherapies.
通过解决活细胞中不同的细胞死亡表型来精确和定量地评估CAR-T细胞诱导的细胞毒性仍然是免疫疗法发展中一个关键的未满足的需求。在单细胞分辨率下区分CAR-T治疗诱导的细胞凋亡和坏死对于阐明细胞毒性机制和预测治疗结果至关重要。然而,大多数活细胞分析缺乏这样做的时空敏感性。在这里,我们提出了一种基因编码的双生物传感器系统,可以同时监测caspase-3/7激活和线粒体完整性,从而实时区分细胞凋亡和坏死。该平台结合了基于fret的caspase传感器(RealCas3)和线粒体靶向的DsRed报告细胞(MitoDsRed),具有显微镜成像和流式细胞术的兼容性。我们将该平台应用于抗egfr CAR-T细胞的功能分析,并揭示了一种双相细胞毒性模式,其标志是早期caspase-3/7诱导的细胞凋亡,随后是延迟坏死。值得注意的是,该系统能够对继发性坏死进行时间分辨检测,这是一种延迟的免疫原性死亡表型,在常规检测中经常被错误分类。开发的平台为免疫效应反应的实时功能表型分析提供了一种强大且可扩展的方法,解决了免疫治疗开发过程中评估细胞死亡机制的关键空白。通过对肿瘤细胞死亡和死亡方式进行时间分辨定量,该双传感器系统为评估和合理设计更安全、更有效的新一代免疫疗法建立了机制框架。
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引用次数: 0
Graphene hybrid nanoprobes for targeted microbial sensing and ultralow-energy, deep-tissue, noninvasive multiphoton imaging in the NIR-I/II region 石墨烯混合纳米探针用于NIR-I/II区域的靶向微生物传感和超低能量、深层组织、无创多光子成像。
IF 10.5 1区 生物学 Q1 BIOPHYSICS Pub Date : 2026-06-01 Epub Date: 2026-02-08 DOI: 10.1016/j.bios.2026.118506
Wen-Shuo Kuo , Yen-Sung Lin , Chia-Yuan Chang , Jiu-Yao Wang , Pei-Chi Chen , Shih-Wen Tseng , Chiao-Yun Lin , Chan-Chi Chang , Shang-Rung Wu
Nitrogen (N) doping and amino functionalization markedly enhance the electron-donating capacity of graphene quantum dots (GQDs), thereby improving charge-transfer efficiency in amino-N-GQDs and yielding substantially superior photophysical performance compared with amino-free N-GQDs and N-free amino-GQDs. Further optimization was achieved through conjugation of amino-N-GQDs with sulfur- and nitrogen-rich polymers, polystyrene sulfonate and polyethylenimine, resulting in amino-N-GQD-polymer nanohybrids with significantly improved optical behavior. These hybrid nanostructures exhibited high quantum yields, excellent photostability, negligible reactive oxygen species generation, and strong two-photon luminescence, positioning them as promising contrast agents for nonlinear bioimaging. To enable molecular specificity, antibody functionalization was incorporated. When conjugated with anti-lipopolysaccharide or anti-TasA antibodies, the nanohybrids selectively targeted Escherichia coli (E. coli) and Bacillus subtilis (B. subtilis), generating bright fluorescence, strong signal intensity, and high signal-to-noise ratios under two-photon excitation. Using a custom-built Ti:sapphire laser system operating at 970 nm (near-infrared-II region), imaging depths of up to 270 μm were achieved with ultralow excitation energies, 42.96 nJ pixel−1 for E. coli and 35.14 nJ pixel−1 for B. subtilis, acquired over 100 scans (total exposure = 0.666 s). The nanohybrids produced two-photon luminescence using only 1/49 and 1/36 of the energy required for cellular autofluorescence, corresponding to ∼2401- and ∼1296-fold signal enhancements, respectively. This remarkable efficiency supports deep, noninvasive imaging and underscores the potential of amino-N-GQD-polymer nanohybrids as versatile near-infrared-I/II-responsive probes for next-generation biomedical imaging applications.
氮(N)掺杂和氨基功能化显著增强了石墨烯量子点(GQDs)的供电子能力,从而提高了氨基-N-石墨烯量子点的电荷转移效率,与无氨基的N-GQDs和无N的氨基-GQDs相比,石墨烯量子点的光物理性能显著提高。通过将氨基- n- gqd与富硫和富氮聚合物、聚苯乙烯磺酸盐和聚乙烯亚胺偶联进一步优化,得到了光学性能显著改善的氨基- n- gqd聚合物纳米杂化体。这些杂化纳米结构表现出高量子产率、优异的光稳定性、可忽略的活性氧生成和强双光子发光,使它们成为非线性生物成像的有前途的造影剂。为了实现分子特异性,结合了抗体功能化。当与抗脂多糖或抗tasa抗体偶联时,纳米杂交体选择性地靶向大肠杆菌(E. coli)和枯草芽孢杆菌(B. subtilis),在双光子激发下产生明亮的荧光,强信号强度和高信噪比。使用定制的Ti:蓝宝石激光系统,工作波长为970 nm(近红外- ii区),在超低激发能下获得了高达270 μm的成像深度,大肠杆菌为42.96 nJ pixel-1,枯草芽孢杆菌为35.14 nJ pixel-1,扫描次数超过100次(总曝光 = 0.666 s)。纳米杂交体产生双光子发光,仅使用细胞自身荧光所需能量的1/49和1/36,分别对应于信号增强的~ 2401和~ 1296倍。这种卓越的效率支持深度、非侵入性成像,并强调了氨基- n - gqd聚合物纳米杂化物作为下一代生物医学成像应用中多功能近红外i / ii响应探针的潜力。
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