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A Unique Prodrug Targeting the Prostate-Specific Membrane Antigen for the Delivery of Monomethyl Auristatin E.
IF 4 2区 化学 Q1 BIOCHEMICAL RESEARCH METHODS Pub Date : 2025-02-19 Epub Date: 2025-01-29 DOI: 10.1021/acs.bioconjchem.4c00297
Hunter N Bomba, Melody D Fulton, Emily A Savoy, Beatrice Langton-Webster, Clifford E Berkman

Monomethyl auristatin E (MMAE) is a promising treatment option for patients diagnosed with prostate cancer (PCa); however, toxicities prevent MMAE from being administered as free drug. No MMAE-based treatment is currently marketed for PCa. Herein, we describe a small-molecule-drug conjugate, CTT2274, for the selective delivery of MMAE. CTT2274 is composed of a prostate-specific membrane antigen (PSMA)-binding scaffold, a biphenyl motif, a pH-sensitive phosphoramidate linker, and MMAE payload. We demonstrate that CTT2274 shows selective binding to PSMA, which is overexpressed on PCa cells, and induces tumor cell death in vitro. In a patient-derived xenograft tumor model of PCa in mice, we show that weekly intravenous dosing of CTT2274 at 3.6 mg/kg for six weeks is superior to treatment with free MMAE at equivalent doses. Mice treated with CTT2274 experienced prolonged tumor suppression and significantly greater overall survival than mice treated with PBS. Additionally, the safety of CTT2274 compared to an equivalent dose of MMAE was assessed in healthy, non-tumor-bearing mice. Our results demonstrate that CTT2274 therapy is as efficacious as MMAE, results in superior overall survival, and has a more favorable safety profile. Together, these data indicate that CTT2274 is a candidate for clinical translation for the treatment of PCa.

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引用次数: 0
Unlocking the Potential of Antimicrobial Peptides: Cutting-Edge Advances and Therapeutic Potential in Combating Bacterial Keratitis.
IF 4 2区 化学 Q1 BIOCHEMICAL RESEARCH METHODS Pub Date : 2025-02-19 DOI: 10.1021/acs.bioconjchem.4c00594
Bingru Xiao, Jie Wang, Jie Xing, Lulu He, Chen Xu, Aiguo Wu, Juan Li

Bacterial keratitis is a prevalent, and severe corneal illness resulting from bacterial pathogens. Failure to administer a timely and suitable therapy may lead to corneal opacity, ulceration, significant vision impairment, or potential blindness. Current clinical interventions for bacterial keratitis involve the administration of topical antimicrobial agents and systemic antibiotics. However, the misuse and overuse of antibiotics have led to the rapid emergence of antibiotic-resistant bacteria. Additionally, the restricted antibacterial spectrum and possible adverse effects of antibiotics have provided considerable obstacles to traditional therapies. This highlights the urgent need for novel and highly effective antimicrobial agents. Antimicrobial peptides (AMPs) are a class of naturally occurring or synthetically designed small molecules that have gained significant attention due to their unique antimicrobial mechanisms and low risk of resistance development. AMPs exhibit promising potential in treating bacterial keratitis through direct antibacterial mechanisms, such as inhibiting cell wall synthesis, disrupting cell membranes, and interfering with nucleic acid metabolism, as well as indirect mechanisms, including modulation of the host immune response. This review provides a comprehensive overview of the antibacterial mechanisms of AMPs and their advancements in the treatment of bacterial keratitis. It emphasizes the role of various modification strategies and artificial-intelligence-assisted design in enhancing the antibacterial efficacy, stability, and biocompatibility of AMPs. Furthermore, this review discusses the latest progress in combining AMPs with delivery systems for improved therapeutic outcomes. Finally, the review highlights the current challenges and future perspectives of AMPs in bacterial keratitis treatment, providing valuable insights for developing novel AMPs with high antibacterial efficacy, stability, and safety for bacterial keratitis therapies.

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引用次数: 0
Quantum Dot Erythropoietin Bioconjugates Enhance EPO-Receptor Clustering on Transfected Human Embryonic Kidney Cells. 量子点促红细胞生成素生物偶联物增强转染人胚胎肾细胞的epo受体聚类。
IF 4 2区 化学 Q1 BIOCHEMICAL RESEARCH METHODS Pub Date : 2025-02-19 Epub Date: 2025-01-21 DOI: 10.1021/acs.bioconjchem.4c00521
Ryan N Porell, Okhil K Nag, Michael H Stewart, Kimihiro Susumu, Eunkeu Oh, James B Delehanty

Erythropoietin (EPO)-induced cellular signaling through the EPO receptor (EPOR) is a fundamental pathway for the modulation of cellular behavior and activity. In our previous work, we showed in primary human astrocytes that the multivalent display of EPO on the surface of semiconductor quantum dots (QDs) mediates augmented JAK/STAT signaling, a concomitant 1.8-fold increase in the expression of aquaporin-4 (AQPN-4) channel proteins, and a 2-fold increase in the AQPN-4-mediated water transport activity. Our hypothesis is that this enhanced signaling involves the simultaneous ligation and clustering of EPOR by QD-EPO conjugates. Here, we utilized a human embryonic kidney (HEK 293T/17) cell line transfected with EPOR fused to enhanced green fluorescent protein (eGFP) to visualize EPOR clustering. We demonstrate that QDs displaying five copies of EPO (bearing a C-terminal 6-histidine tract) on the nanoparticle surface induce a 1.8-fold increase in EPOR clustering compared to monomeric EPO at the same concentration. Our findings confirm the critical role played by the multivalent display of EPO in mediating clustering of the EPOR. More generally, these results illustrate the capability of nanoparticle-growth factor bioconjugates to control the activity of cognate receptors and the important role played by multivalent display in the modulation of selective cellular delivery and signaling.

促红细胞生成素(EPO)通过促红细胞生成素受体(EPOR)诱导的细胞信号传导是调节细胞行为和活性的基本途径。在我们之前的工作中,我们在人星形胶质细胞中发现,半导体量子点(QDs)表面的EPO多价显示介导了JAK/STAT信号的增强,同时水通道蛋白-4 (AQPN-4)通道蛋白的表达增加了1.8倍,AQPN-4介导的水运输活性增加了2倍。我们的假设是,这种增强的信号涉及QD-EPO偶联物同时连接和聚集EPOR。在这里,我们利用转染了EPOR与增强绿色荧光蛋白(eGFP)融合的人胚胎肾(HEK 293T/17)细胞系来观察EPOR聚类。我们证明,在纳米颗粒表面显示5个EPO拷贝(带有c端6-组氨酸基团)的量子点,与相同浓度的单体EPO相比,诱导EPO聚类增加1.8倍。我们的研究结果证实了EPO的多价显示在介导EPOR聚集中所起的关键作用。更广泛地说,这些结果说明了纳米颗粒-生长因子生物偶联物控制同源受体活性的能力,以及多价显示在选择性细胞传递和信号传导的调节中发挥的重要作用。
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引用次数: 0
Synthesis and Biological Evaluation of Bile Acid-Triclosan Conjugates: A Study on Antibacterial, Antibiofilm, and Molecular Docking.
IF 4 2区 化学 Q1 BIOCHEMICAL RESEARCH METHODS Pub Date : 2025-02-19 Epub Date: 2025-01-22 DOI: 10.1021/acs.bioconjchem.4c00539
Neha V Rathod, Satyendra Mishra

This work describes the synthesis, characterization, and antibacterial properties of four bile acid-triclosan conjugates. The in vitro antibacterial activity of synthetic bile acid-triclosan conjugates was investigated against a panel of Gram-positive and Gram-negative bacteria. Conjugates 3 and 4 show high activity against Escherichia coli (ATCC25922), with IC50 values of 2.94 ± 0.7 and 1.51 ± 0.05 μM, respectively. Conjugate 4 demonstrated 9 times the activity of triclosan (6.77 μM) and 18 times the potency of kanamycin, a well-known antibiotic. Compound 3 showed higher potential activity against all evaluated strains, including Bacillus megaterium (IC50: 3.05 ± 0.02), Bacillus amyloquefaciens (IC50: 8.79 ± 0.01), Serratia marcescens (IC50: 6.77 ± 0.4), and E. coli (IC50: 1.51 ± 0.05 μM). These findings indicate that it has broad-spectrum antibacterial activity. Bile acid-triclosan conjugates prevent biofilms by up to 99% at low doses (conjugates 4; 4.16 ± 0.8 μM), compared to triclosan. Conjugate 5 was most potent against B. amyloquefaciens (IC50 = 5.23 ± 0.2 μM), while conjugate 4 was most effective against B. megaterium (IC50 = 4.16 ± 0.8 μM) in biofilm formation. These conjugates inhibit biofilm formation by limiting the extracellular polymeric substance generation. The in vitro antibacterial study revealed that bile acid-triclosan conjugates were more effective than the parent molecule triclosan at inhibiting bacterial growth and biofilm formation against both Gram-positive and Gram-negative bacteria.

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引用次数: 0
Targeted NIR Fluorescent Mechanically Interlocked Molecules-Peptide Bioconjugate for Live Cancer Cells Submitochondrial Stimulated Emission Depletion Super-Resolution Microscopy. 靶向近红外荧光机械互锁分子-肽生物偶联物用于活癌细胞亚线粒体受激辐射耗竭超分辨显微镜。
IF 4 2区 化学 Q1 BIOCHEMICAL RESEARCH METHODS Pub Date : 2025-02-19 Epub Date: 2025-01-10 DOI: 10.1021/acs.bioconjchem.4c00476
Samiran Kar, Rabi Sankar Das, Tapas Bera, Shreya Das, Ayan Mukherjee, Aniruddha Mondal, Arunima Sengupta, Samit Guha

Herein, a water-soluble, ultrabright, near-infrared (NIR) fluorescent, mechanically interlocked molecules (MIMs)-peptide bioconjugate is designed with dual targeting capabilities. Cancer cell surface overexpressed αVβ3 integrin targeting two RGDS tetrapeptide residues is tethered at the macrocycle of MIMs-peptide bioconjugate via Cu(I)-catalyzed click chemistry on the Wang resin, and mitochondria targeting lipophilic cationic TPP+ functionality is conjugated at the axle dye. Living carcinoma cell selective active targeting, subsequently cell penetration, mitochondrial imaging, including the ultrastructure of cristae, and real-time tracking of malignant mitochondria by MIMs-peptide bioconjugate (RGDS)2-Mito-MIMs-TPP+ are established by stimulated emission depletion (STED) super-resolved fluorescence microscopy. Water-soluble NIR (RGDS)2-Mito-MIMs-TPP+ is an effective class of MIMs-peptide bioconjugate with promising photophysics; for instance, remarkable photostability and thermal stability, strong and narrow NIR abs/em bands with high quantum yield, ultrabrightness, decent fluorescence lifetime, reasonable stability against cellular nucleophiles, biocompatibility, noncytotoxicity, and dual-targeted living cancer cell submitochondrial imaging ability are all indispensable criteria for targeted super-resolved STED microscopy.

本文设计了一种水溶性、超亮、近红外(NIR)荧光、机械互锁分子(mim)-肽生物偶联物,具有双重靶向能力。癌细胞表面过表达的αVβ3整合素靶向两个RGDS四肽残基,通过Cu(I)催化的click化学在Wang树脂上拴在mims -肽生物偶联物的大环上,靶向亲脂性阳离子TPP+功能的线粒体在轴染料上偶联。利用受激发射损耗(STED)超分辨荧光显微镜,建立了活癌细胞选择性活性靶向、细胞穿透、线粒体成像(包括嵴超微结构)和mim -肽生物偶联物(RGDS)2- mito - mim - tpp +对恶性线粒体的实时跟踪。水溶性NIR (RGDS)2- mito - mim - tpp +是一类有效的mim -肽生物偶联物,具有良好的光物理特性;例如,卓越的光稳定性和热稳定性,高量子产率的强而窄的近红外abs/em波段,超亮度,良好的荧光寿命,对细胞亲核试剂的合理稳定性,生物相容性,非细胞毒性以及双靶向活癌细胞亚线粒体成像能力都是靶向超分辨STED显微镜不可或缺的标准。
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引用次数: 0
Site-Specific Molecular Engineering of Nanobody-Glucoside Conjugates for Enhanced Brain Tumor Targeting. 纳米糖苷偶联物增强脑肿瘤靶向的位点特异性分子工程。
IF 4 2区 化学 Q1 BIOCHEMICAL RESEARCH METHODS Pub Date : 2025-02-19 Epub Date: 2025-01-09 DOI: 10.1021/acs.bioconjchem.4c00555
Siyu Zhou, Xiaofeng Fang, Yunhe Luo, Yicheng Yang, Weijun Wei, Gang Huang, Xuanjun Zhang, Changfeng Wu

Nanobodies play an increasingly prominent role in cancer imaging and therapy. However, their in vivo efficacy is often constrained by inadequate tumor penetration and rapid clearance from the bloodstream, particularly in brain tumors due to the intractable blood-brain barrier (BBB). Glycosylation is a favorable strategy for modulating the biological functions of nanobodies, including permeability and pharmacokinetics, but it also leads to heterogeneous glycan structures, which affect the targeting ability, stability, and quality of nanobodies. Here, we describe a post-translational modification strategy to produce precisely engineered and homogeneous nanobody-glucoside conjugates for effective BBB penetration and brain tumor targeting. Specifically, we employ an enzymatic method and click chemistry to functionalize nanobodies with glucoside and poly(ethylene glycol) (PEG), facilitating efficient transcytosis into the brain via glucose transporter-1 (GLUT1). Furthermore, we rationally select a near-infrared (NIR) fluorophore for labeling to maintain the metabolic pathway and biodistribution of nanobodies and assess their potency in two tumor models. The resulting nanobody-glucoside conjugates demonstrate a remarkable increase in BBB penetration and brain tumor accumulation, which are ∼2.9-fold higher in the transgenic mouse model and ∼5.7-fold higher in the orthotopic glioma model compared to unmodified nanobodies. This study provides a promising approach for the production of nanobody therapeutic agents for central nervous system (CNS) delivery.

纳米体在肿瘤成像和治疗中发挥着越来越重要的作用。然而,它们在体内的疗效往往受到肿瘤渗透不足和血液快速清除的限制,特别是在脑肿瘤中,由于顽固的血脑屏障(BBB)。糖基化是调节纳米体生物功能(包括渗透性和药代动力学)的一种有利策略,但它也会导致糖基结构不均匀,从而影响纳米体的靶向能力、稳定性和质量。在这里,我们描述了一种翻译后修饰策略,以生产精确工程和均匀的纳米-糖苷偶联物,用于有效穿透血脑屏障和靶向脑肿瘤。具体来说,我们采用酶和点击化学的方法,用葡萄糖苷和聚乙二醇(PEG)功能化纳米体,促进通过葡萄糖转运蛋白-1 (GLUT1)高效地转吞进入大脑。此外,我们合理选择近红外荧光团进行标记,以维持纳米体的代谢途径和生物分布,并评估其在两种肿瘤模型中的效力。由此产生的纳米体-葡萄糖苷偶联物显示出血脑屏障渗透和脑肿瘤积累的显著增加,与未修饰的纳米体相比,转基因小鼠模型中的血脑屏障渗透和脑肿瘤积累增加了约2.9倍,在原位胶质瘤模型中增加了约5.7倍。该研究为生产用于中枢神经系统(CNS)递送的纳米体治疗剂提供了一条有前途的途径。
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引用次数: 0
5'-Amino-Formyl-Thieno[3,2-b]thiophene End-Label for On-Strand Synthesis of Far-Red Fluorescent Molecular Rotors and pH-Responsive Probes. 5'-氨基甲酰基-噻吩[3,2-b]噻吩末端标记用于远红色荧光分子转子和ph响应探针的链上合成。
IF 4 2区 化学 Q1 BIOCHEMICAL RESEARCH METHODS Pub Date : 2025-02-19 Epub Date: 2025-01-21 DOI: 10.1021/acs.bioconjchem.4c00457
Ryan E Johnson, Keenan T Regan, Richard A Manderville

The ability to label synthetic oligonucleotides with fluorescent probes has greatly expanded their nanotechnological applications. To continue this expansion, it is essential to develop approachable, modular, and tunable fluorescent platforms. In this study, we present the synthesis and incorporation of an amino-formyl-thieno[3,2-b]thiophene (AFTh2) handle at the 5'-position of DNA oligonucleotides. The 5'-AFTh2 end-label participates in both on-strand Knoevenagel and heterocyclization reactions, yielding far-red hemicyanines and pH-responsive probes with pKa values in the biological regime. The Knoevenagel products, designated 5'-ATh2Btz and 5'-ATh2Ind, demonstrate excitation maxima beyond 640 nm with brightness up to ∼50,000 M-1 cm-1. Notably, 5'-ATh2Btz demonstrates strong topology sensitivity, allowing it to probe transitions from duplex- to single-strand (SS)/G-quadruplex (GQ) topologies with an ∼9-fold increase in fluorescence in the absence of quenchers. In contrast, the heterocyclization product, 5'-ATh2BIM, displays visible excitation and emission and is weakly fluorescent in basic solution. Upon lowering the pH from ∼8 to 5, this probe undergoes an unprecedented 400-fold light-up. Additionally, attaching 5'-ATh2BIM to a polymorphic GQ allows for a shift in pKa by ∼1.5 pH units simply by changing topology. The performance of the probes has been demonstrated in various contexts, including GQs, i-motifs, duplexes, and SS oligonucleotides. Their performance should facilitate the development of new DNA-based sensing platforms.

用荧光探针标记合成寡核苷酸的能力极大地扩展了它们的纳米技术应用。为了继续这种扩展,必须开发可接近的、模块化的和可调的荧光平台。在这项研究中,我们提出了在DNA寡核苷酸的5'位置合成并掺入氨基甲酰基噻吩[3,2-b] (AFTh2)处理。5'-AFTh2末端标签参与链上Knoevenagel和杂环化反应,产生远红色半菁氨酸和ph响应探针,在生物学机制中具有pKa值。Knoevenagel的产品,命名为5'-ATh2Btz和5'-ATh2Ind,显示出超过640 nm的最大激发,亮度高达~ 50,000 M-1 cm-1。值得注意的是,5'- ath2btz表现出很强的拓扑灵敏度,允许它探测从双链到单链(SS)/ g -四链(GQ)拓扑的转变,在没有猝灭剂的情况下荧光增加了约9倍。而杂环化产物5′-ATh2BIM在碱性溶液中表现出明显的激发和发射,荧光弱。当pH值从~ 8降低到5时,该探针经历了前所未有的400倍发光。此外,将5'-ATh2BIM连接到多态GQ上,只需改变拓扑结构,就可以将pKa转移约1.5个pH单位。探针的性能已在各种情况下得到证明,包括gq, i-motif,双工和SS寡核苷酸。它们的性能将促进新的基于dna的传感平台的发展。
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引用次数: 0
The Effect of the Size of Gold Nanoparticle Contrast Agents on CT Imaging of the Gastrointestinal Tract and Inflammatory Bowel Disease. 纳米金造影剂粒径对胃肠道及炎症性肠病CT成像的影响
IF 4 2区 化学 Q1 BIOCHEMICAL RESEARCH METHODS Pub Date : 2025-02-19 Epub Date: 2025-01-09 DOI: 10.1021/acs.bioconjchem.4c00507
Derick N Rosario-Berríos, Amanda Pang, Leening P Liu, Portia S N Maidment, Johoon Kim, Seokyoung Yoon, Lenitza M Nieves, Katherine J Mossburg, Andrew Adezio, Peter B Noël, Elizabeth M Lennon, David P Cormode

Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD). CT imaging with contrast agents is commonly used for visualizing the gastrointestinal (GI) tract in UC patients. Contrast agents that provide enhanced imaging performance are highly valuable in this field. Recent studies have made significant progress in developing better contrast agents for imaging the gastrointestinal tract using nanoparticles. However, the impact of nanoparticle size on this application remains unexplored. Gold nanoparticles (AuNPs) serve as an ideal model to investigate the effect of nanoparticle size on imaging of the gastrointestinal tract due to their controllable synthesis across a broad size range. In this study, we synthesized AuNPs with core sizes ranging from 5 to 75 nm to examine the effect of the size in this setting. AuNPs were coated with poly(ethylene glycol) (PEG) to enhance stability and biocompatibility. In vitro tests show that gold nanoparticles are cytocompatible with macrophage cells (∼100% cell viability) and remain stable under acidic conditions, with no significant size changes over time. Phantom imaging studies using a clinical CT scanner indicated that there was no effect of nanoparticle size on CT contrast production, as previously demonstrated. In vivo imaging using a mouse model of acute colitis revealed a strong contrast generation throughout the GI tract for all agents tested. For the most part, in vivo contrast was independent of AuNP size, although AuNP outperformed iopamidol (a clinically approved control agent). In addition, differences in attenuation trends were observed between healthy and colitis mice. We also observed almost complete clearance at 24 h of all formulations tested (less than 0.7% ID/g was retained), supporting their value as a model platform for studying nanoparticle behavior in imaging. In conclusion, this study highlights the potential of nanoparticles as effective contrast agents for CT imaging of the gastrointestinal tract (GIT) in the UC. Further systemic research is needed to explore contrast agents that can specifically image disease processes in this disease setting.

溃疡性结肠炎是一种慢性炎症性肠病(IBD)。CT造影剂成像通常用于UC患者胃肠道的显像。增强成像性能的造影剂在这一领域非常有价值。最近的研究在开发用于胃肠道成像的纳米颗粒造影剂方面取得了重大进展。然而,纳米颗粒尺寸对这一应用的影响仍未被探索。金纳米颗粒(AuNPs)是研究纳米颗粒大小对胃肠道成像影响的理想模型,因为它们可以在很宽的尺寸范围内可控合成。在这项研究中,我们合成了核心尺寸在5到75 nm之间的AuNPs,以检验大小在这种情况下的影响。AuNPs包被聚乙二醇(PEG)以提高稳定性和生物相容性。体外实验表明,金纳米颗粒与巨噬细胞具有细胞相容性(约100%的细胞活力),在酸性条件下保持稳定,随着时间的推移没有明显的大小变化。使用临床CT扫描仪的幻影成像研究表明,纳米颗粒大小对CT造影剂的产生没有影响,正如之前所证明的那样。使用小鼠急性结肠炎模型的体内成像显示,所有测试的药物在整个胃肠道中产生强烈的造影剂。在大多数情况下,体内对比与AuNP大小无关,尽管AuNP优于iopamidol(一种临床批准的对照剂)。此外,在健康小鼠和结肠炎小鼠之间观察到衰减趋势的差异。我们还观察到所有测试的配方在24小时几乎完全清除(保留小于0.7% ID/g),支持它们作为研究纳米颗粒成像行为的模型平台的价值。总之,本研究强调了纳米颗粒作为UC胃肠道(GIT) CT成像有效造影剂的潜力。需要进一步的系统研究来探索造影剂,可以特异性地显示这种疾病的疾病过程。
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引用次数: 0
Biomechanical and Functional Features of the Carrier Erythrocytes Prolonging Circulation Time of Biotherapeutic Targeted to Glycophorin A.
IF 4 2区 化学 Q1 BIOCHEMICAL RESEARCH METHODS Pub Date : 2025-02-19 Epub Date: 2025-01-27 DOI: 10.1021/acs.bioconjchem.4c00522
Alina D Peshkova, Taylor V Brysgel, Parth Mody, Jia Nong, Zhicheng Wang, Jacob W Myerson, Rustem I Litvinov, John W Weisel, Jacob S Brenner, Patrick M Glassman, Oscar A Marcos-Contreras, Vladimir R Muzykantov

Red blood cells (RBCs) serve as natural transporters and can be modified to enhance the pharmacokinetics and pharmacodynamics of a protein cargo. Affinity targeting of Factor IX (FIX) to the RBC membrane is a promising approach to improve the (pro)enzyme's pharmacokinetics. For RBC targeting, purified human FIX was conjugated to the anti-mouse glycophorin A monoclonal antibody Ter119. The goal of this study was to characterize the activity of the FIX-Ter119 conjugate and efficacy of its loading on RBCs, as well as to investigate the biodistribution, pharmacokinetics, and various biological properties of the loaded RBCs. Mouse RBCs were incubated with the Ter119-FIX conjugate, where adding 10,000 molecules per RBC resulted in 37% binding (4K/RBC), and 50,000 molecules per RBC resulted in 34% binding (17K/RBC). The pharmacokinetics (PK) profile showed that more than 90% of the Ter119-FIX conjugate was associated with RBCs and circulated stably bound to the RBCs for 24 h, increasing the area under the PK curve 7.6 times vs free FIX. Ter119-FIX loaded RBCs have specific procoagulant FIXa activity, including promotion of thrombin generation and acceleration of clotting in FIX-deficient plasma. Morphological characterization shows that Ter119-FIX-loaded RBCs undergo a shape change, with an increased fraction of echinocytes and spheroidal RBCs. Ektacytometry and electron microscopy assessment of RBC compressibility reveal a dose-dependent reduction in the deformability of RBCs loaded with Ter119-FIX. In conclusion, RBCs loaded with Ter119-FIX have the potential to serve as prohemostatic agents, but their reduced deformability warrants further engineering of Ter119-FIX to improve the safety profile.

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引用次数: 0
Nanoscale Effects in the Room-Temperature UV-Visible Photoluminescence from Silica Particles and Its Cancer Cell Imaging.
IF 4 2区 化学 Q1 BIOCHEMICAL RESEARCH METHODS Pub Date : 2025-02-19 Epub Date: 2025-01-29 DOI: 10.1021/acs.bioconjchem.4c00420
Divya Rani, Deepika Singh, Anil Kumar, Monika Dhiman, Anjali Saini, Partho Biswas, Rachana Rachana, Partha Roy, Mrinal Dutta, Arup Samanta

Silica nano/microparticles have generated significant interest for the past decades, emerging as a versatile material with a wide range of applications in photonic crystals, bioimaging, chemical sensors, and catalysis. This study focused on synthesizing silica nano/microparticles ranging from 20 nm to 1.2 μm using the Stöber and modified Stöber methods. The particles exhibited photoluminescence emission across a UV-visible range, specifically in the UV (∼290, ∼327, ∼339, and ∼377 nm), blue (∼450 nm), green (∼500 nm), yellow (∼576 nm), and red (∼634 nm) range of the electromagnetic spectrum. These emissions are due to radiative relaxation processes involving oxygen-deficient centers arising due to unrelaxed oxygen vacancies, strong interacting surface silanols, 2-fold coordinated silicon, self-trapped excitons, hydrogen-related species, strain-induced defects, and nonbridging oxygen hole centers excited via two-photon and single photon absorption. The increased PL intensity with a decreasing particle size was attributed to higher concentrations of defect sites in the case of smaller-sized particles. The MTT assay, AO/EB staining, and the DCFDA assay confirmed the biocompatible nature of silica particles in the HepG2 cell line. In addition, the cell viability assay in a normal cell line (HEK293) also showed no substantial cell death. Successful bioimaging of HepG2 cells was performed with silica nano/microparticles, which exhibited blue and green fluorescence, along with Hoechst33258 dye. Even though 20 nm-sized silica particles showed higher PL emission, particles sized above 20 nm showed better fluorescence in HepG2 cells, citing their potential in in vitro bioimaging applications.

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Bioconjugate Chemistry
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