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Expandable rotational origami nano-boxes made by giant shape amphiphile 巨型双亲化合物制成的可扩展旋转折纸纳米盒
IF 13.2 1区 材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY Pub Date : 2024-08-28 DOI: 10.1016/j.nantod.2024.102458
Jia Chen , Haoru Zhao , Dandan Gu , Yangshuang Xiang , Xiaoze Jiang , Chien-Lung Wang , Liping Zhu , Bin Sun , Meifang Zhu

Dynamic cavity is widespread in living matter and supramolecular scaffolds. Generally speaking, flexible building block as a segment is used to realize dynamic cavities building in artificial molecules and materials. However, the incorporation of rigid synthetic supramolecular scaffolds with flexible cavity motion remains rare. Inspired by rotational origami patterns, giant shape amphiphile (GSA), POSS-NDI-POSS (PNP), assembled into an origami nano-box with feature of rotational expansion. The open/close of cavity and size control of PNP host can be adjusted by rotational offset between adjacent PNP in supramolecule entities. The rotational offset of 150°, 130° and 0° were observed when the host nano-box presented close, half-open and fully-open state, respectively. The rotational expansion of PNP trigged by gaseous arenes makes PNP as a novel nonporous crystal. Compared with conformation change in flexible building segment, rotational expansion in acyclic host (PNP) provides a new strategy for the development of rigid segment to build adaptive host-guest recognition.

动态空腔广泛存在于生命物质和超分子支架中。一般来说,人造分子和材料中的动态空腔构建都是以柔性构件为片段来实现的。然而,将刚性合成超分子支架与柔性空腔运动结合在一起的情况仍然很少见。受旋转折纸图案的启发,巨型双亲化合物(GSA)、POSS-NDI-POSS(PNP)组装成了具有旋转扩展功能的折纸纳米盒。超分子实体中相邻 PNP 之间的旋转偏移可调节空腔的开闭和 PNP 主控体的大小。当主纳米盒呈现关闭、半开和全开状态时,旋转偏移分别为 150°、130° 和 0°。气态烯引发的 PNP 旋转扩展使 PNP 成为一种新型无孔晶体。与柔性结构段的构象变化相比,无环宿主(PNP)的旋转扩展为刚性结构段的发展提供了一种新策略,以建立适应性的宿主-访客识别。
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引用次数: 0
Three-dimensional hydrogel membranes for boosting osmotic energy conversion: Spatial confinement and charge regulation induced by zirconium ion crosslinking 用于促进渗透能量转换的三维水凝胶膜:锆离子交联诱导的空间限制和电荷调节
IF 13.2 1区 材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY Pub Date : 2024-08-28 DOI: 10.1016/j.nantod.2024.102468
Caiqin Wu , Jian Wang , Rong Wu , Huan Zeng , Xianfei Chen , Chenling Yao , Jialing Zhou , Xiang-Yu Kong , Liping Wen , Lei Jiang

Ion-exchange membranes have been widely used to harvest osmotic energy in the past decades. However, conventional ion-exchange membranes suffer from low output power and poor conversion efficiency due to their limited pores and high membrane resistance. Herein, a sodium alginate (SA)/3-sulfopropyl acrylate potassium salt (SPAK) hydrogel membrane which has good cationic selectivity and can effectively harvest osmotic energy is designed, yielding a maximum power density of 16.44 W/m2 under a 50-fold NaCl concentration gradient and 36.85 W/m2 with ion selectivity of 0.73 at 500-fold. Furthermore, by introducing Zr4+, post-crosslinking reaction was employed to prepare tougher hydrogel membranes at room temperature for breaking a trade-off between selectivity and permeability, boosting a maximum power density up to 25.07 W/m2 under a 50-fold NaCl concentration gradient and 121.66 W/m2 with a high cation selectivity of 0.87 at 500-fold. Importantly, the resultant SA/SPAK/Zr4+ membrane reveals excellent osmotic energy harvesting property with the largest thickness of 500 μm, exceeding other reported porous nanofluidic membranes. Theoretical calculations correlate the enhanced power density of SA/SPAK/Zr4+ membranes with the enriched Cl- and smaller pore size after the introduction of Zr4+. This work paves an avenue to design and develop the 3D hydrogel membranes for high-performance osmotic energy generators.

过去几十年来,离子交换膜被广泛用于获取渗透能。然而,传统的离子交换膜由于孔隙有限、膜阻力大,因此输出功率低、转换效率差。本文设计了一种海藻酸钠(SA)/3-磺丙基丙烯酸酯钾盐(SPAK)水凝胶膜,它具有良好的阳离子选择性,能有效收集渗透能,在 50 倍 NaCl 浓度梯度下的最大功率密度为 16.44 W/m2,在 500 倍离子选择性为 0.73 时的最大功率密度为 36.85 W/m2。此外,通过引入 Zr4+,利用后交联反应在室温下制备出更坚韧的水凝胶膜,打破了选择性和渗透性之间的权衡,在 50 倍 NaCl 浓度梯度下,最大功率密度提高到 25.07 W/m2,在 500 倍离子浓度梯度下,最大功率密度提高到 121.66 W/m2,阳离子选择性高达 0.87。重要的是,所制备的 SA/SPAK/Zr4+ 膜具有出色的渗透能收集特性,最大厚度达 500 μm,超过了其他已报道的多孔纳米流体膜。理论计算表明,SA/SPAK/Zr4+ 膜功率密度的提高与引入 Zr4+ 后富集的 Cl- 和更小的孔径有关。这项工作为设计和开发用于高性能渗透能量发生器的三维水凝胶膜铺平了道路。
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引用次数: 0
Carbon nitride nanosheets induce pulmonary surfactant deposition via dysfunction of alveolar secretion and clearance 氮化碳纳米片通过肺泡分泌和清除功能障碍诱导肺表面活性物质沉积
IF 13.2 1区 材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY Pub Date : 2024-08-27 DOI: 10.1016/j.nantod.2024.102457
Mingyue Wang , Xiaoya Ji , Longwei Wang , Xin Li , Huan Lin , Jianzhong Zhang , Haonan Li , Yongfeng Lin , Leon Gradon , Yuxin Zheng , Jing Liu , Jinglong Tang

Graphitic carbon nitride is a new type of carbon-based nanomaterial with superior properties and great potential for application, which raised great concerns about their environmental and occupational exposure. Graphitic carbon nitride has been reported to accumulate in the lung potentially, however, the respiratory hazard effect of graphitic carbon nitride is still unknown. In the present study, we reported that graphitic carbon nitride (g-CN) and its doped variant sulfur doped graphitic carbon nitride (S-g-CN) nanosheets inhalation induced pulmonary inflammation, increased the production of pulmonary surfactant in alveolar type II epithelial cells, accompanied by the upregulation of lipids transporter expression levels in alveolar macrophages to clear excessive pulmonary surfactant in the alveolar. Further investigation found that the internalization of g-CN and S-g-CN prevented lipid phagocytosis and metabolic processes in alveolar macrophages, ultimately leading to the deposition of proteins and phospholipids in the lung. Furthermore, we found that g-CN was more robust in inhalation toxicity compared to sulfur doped form, which meant the doping of sulfur in graphitic carbon nitride reduced hazardous effects on the respiratory system. In summary, our study demonstrated that inhalation of graphitic carbon nitride nanosheets caused the deposition of pulmonary surfactants in lung, providing an insightful reference for pulmonary toxicity assessment of graphitic carbon nitride.

氮化石墨碳是一种新型碳基纳米材料,具有优越的性能和巨大的应用潜力,这引起了人们对其环境和职业暴露的极大关注。据报道,氮化石墨有可能在肺部蓄积,但氮化石墨对呼吸系统的危害尚不清楚。在本研究中,我们发现石墨氮化碳(g-CN)及其掺杂变体掺硫石墨氮化碳(S-g-CN)纳米片吸入后会诱发肺部炎症,增加肺泡 II 型上皮细胞肺表面活性物质的产生,同时上调肺泡巨噬细胞中脂类转运体的表达水平,以清除肺泡中过多的肺表面活性物质。进一步研究发现,g-CN 和 S-g-CN 的内化阻止了肺泡巨噬细胞的脂质吞噬和代谢过程,最终导致蛋白质和磷脂在肺部沉积。此外,我们还发现,与掺硫形式相比,g-CN 的吸入毒性更强,这意味着在石墨氮化碳中掺硫可减少对呼吸系统的危害。总之,我们的研究表明,吸入氮化石墨碳纳米片会导致肺表面活性物质在肺部沉积,为氮化石墨碳的肺毒性评估提供了有价值的参考。
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引用次数: 0
DNA self-assembly-mediated high drug-antibody ratio ADC platform for targeted tumor therapy and imaging 用于肿瘤靶向治疗和成像的 DNA 自组装介导的高药物抗体比 ADC 平台
IF 13.2 1区 材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY Pub Date : 2024-08-27 DOI: 10.1016/j.nantod.2024.102459
Shijie Jin , Xinlei Zhuang , Yingchun Xu , Guangjun Nie , Shuqing Chen , Liqiang Pan

Antibody-drug conjugates (ADCs) achieve therapeutic effects through toxin delivery inside cells, targeting high-abundance antigens. However, tumor heterogeneity and the low abundance of tumor-specific antigens underscore the urgent requirement for developing a flexible, multifunctional, and high-capacity drug-delivery platform. The current study developed a self-assembled ADC platform called the high drug–antibody-ratio ADC (HD-ADC). Cytotoxic payloads were efficiently conjugated into a 12-arm deoxyribonucleic acid (DNA) branched junction via DNA-mediated precise self-assembly to achieve a high drug–antibody ratio (DAR). Anti-EGFR HD-ADC showed strong efficacy in causing cytotoxicity and suppressing tumor growth in an A431 xenograft mouse model. Furthermore, the Cy5-conjugated HD-ADC platform was a simple and effective method for improving fluorescent signal detection, enabling the detection of targets—such as neoantigens—with ultralow-expression levels. The HD-ADC platform supports the assembly of various functional components, providing the foundation for usage across multiple antibody-mediated targeted therapies and diagnostics.

抗体药物共轭物(ADCs)通过在细胞内靶向高丰度抗原输送毒素来达到治疗效果。然而,由于肿瘤的异质性和肿瘤特异性抗原的低丰度,迫切需要开发一种灵活、多功能、高容量的给药平台。本研究开发了一种自组装 ADC 平台,称为高药物抗体比 ADC(HD-ADC)。通过DNA介导的精确自组装,细胞毒性有效载荷被高效地连接到12臂脱氧核糖核酸(DNA)支链结中,从而实现了高药物抗体比(DAR)。抗 EGFR HD-ADC 在 A431 异种移植小鼠模型中显示出强大的细胞毒性和抑制肿瘤生长的功效。此外,Cy5共轭HD-ADC平台是一种简单有效的荧光信号检测方法,可用于检测超低表达水平的靶标(如新抗原)。HD-ADC 平台支持各种功能组件的组装,为多种抗体介导的靶向治疗和诊断奠定了基础。
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引用次数: 0
Construction of drug-free sodium bicarbonate nanoparticles with high water-tolerance for gas therapy to selectively induce non-apoptotic death of cancer cells 构建具有高耐水性的无药碳酸氢钠纳米颗粒,用于气体疗法,选择性诱导癌细胞非凋亡死亡
IF 13.2 1区 材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY Pub Date : 2024-08-27 DOI: 10.1016/j.nantod.2024.102463
Jinlian He, Xinyi Dai, Ziyang Wang, Jingjie Ye, Jiangbo Wang, Jun Feng, Xian-Zheng Zhang

Developing drug-free nanotherapeutics is extremely appealing provided they could achieve effective therapeutic performances. This study proposes a sodium bicarbonate-dependent gas therapy modality targeting fragile lysosomes of cancer cells through carbon dioxide-induced lysosomal rupture. Interestingly, we reveal that this gas therapy induces cell death through the combination of necrosis, pyroptosis and ferroptosis, rather than the conventional apoptosis pathway. Notably, the high water-solubility of sodium bicarbonate presents a significant challenge in engineering its nanotherapeutics that require long-term water-tolerance for its intravenous delivery. To address this issue, an EPDPPP approach is here developed under aqueous conditions. Without any anticancer drugs, the sodium bicarbonate nanoparticles alone can selectively kill cancer cells with high specificity. Thanks to the high water tolerance, the sodium bicarbonate nanoparticles coated with cancer cell membranes have shown favorable performance in targeting and inhibiting tumors after intravenous administration. This water-tolerant sodium bicarbonate nanoplatform is expected to have potential applications in various medical fields, including the targeted gas therapy. Additionally, this study may suggest a viable direction for developing water-tolerant nanoparticles derived from water-soluble inorganic salts.

开发不含药物的纳米疗法极具吸引力,前提是它们能实现有效的治疗效果。本研究提出了一种依赖碳酸氢钠的气体疗法模式,通过二氧化碳诱导溶酶体破裂,靶向癌细胞的脆弱溶酶体。有趣的是,我们发现这种气体疗法通过细胞坏死、热凋亡和铁凋亡的组合而非传统的细胞凋亡途径诱导细胞死亡。值得注意的是,碳酸氢钠的高水溶性给需要长期耐水才能进行静脉注射的纳米疗法的工程设计带来了巨大挑战。为解决这一问题,本文开发了一种在水性条件下的 EPDPPP 方法。在不使用任何抗癌药物的情况下,仅碳酸氢钠纳米粒子就能以高度特异性选择性地杀死癌细胞。由于碳酸氢钠纳米粒子具有很高的耐水性,因此在静脉注射后,涂有癌细胞膜的碳酸氢钠纳米粒子在靶向和抑制肿瘤方面表现出良好的性能。这种耐水性碳酸氢钠纳米平台有望应用于各种医疗领域,包括靶向气体疗法。此外,这项研究还为开发源自水溶性无机盐的耐水纳米粒子提供了一个可行的方向。
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引用次数: 0
Interface engineering for manipulating the zinc deposition and achieving stable zinc ion batteries 操纵锌沉积和实现稳定锌离子电池的界面工程学
IF 13.2 1区 材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY Pub Date : 2024-08-26 DOI: 10.1016/j.nantod.2024.102461
Weihua Zhou , Ziming Wan , Junrun Feng , Zhangxiang Hao

The aqueous zinc-ion batteries (AZIBs) exhibit promising prospects for large-scale energy storage applications, owing to their notable advantages in terms of safety, abundant reserves of raw materials, and high energy density. However, dendrite growth, hydrogen evolution, and side reaction phenomena arising from the zinc anode side seriously hinder its further development in practical application. To solve these problems, many solutions have been proposed, including the addition of additives in the electrolyte, the design of zinc anode structure, etc., which have made great progress in the past few years. Among them, anode modification of zinc is considered one of the effective means to solve these issues. Herein, we first analyzed the causes of dendrite growth, hydrogen evolution, and side reactions in the presence of zinc anode. Then, we introduce the improved methods for layer coating, alloy anodes, and acid treatment, and provide a comprehensive and in-depth summary of the respective operational principles of these three methods. Finally, we provide a perspective for further development and research of high-performance aqueous zinc-ion batteries.

锌离子水电池(AZIBs)具有安全、原材料储量丰富、能量密度高等显著优势,在大规模储能应用方面前景广阔。然而,锌阳极侧产生的枝晶生长、氢进化和副反应现象严重阻碍了其在实际应用中的进一步发展。为了解决这些问题,人们提出了许多解决方案,包括在电解液中添加添加剂、设计锌阳极结构等,在过去几年中取得了很大进展。其中,锌阳极改性被认为是解决这些问题的有效手段之一。在此,我们首先分析了锌阳极存在树枝状晶生长、氢进化和副反应的原因。然后,我们介绍了层涂层、合金阳极和酸处理的改进方法,并对这三种方法各自的工作原理进行了全面深入的总结。最后,我们对高性能锌离子水电池的进一步开发和研究提出了展望。
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引用次数: 0
Understanding of the irradiation response of Cr-based ATF coatings using in-situ TEM 利用原位 TEM 了解铬基 ATF 涂层的辐照响应
IF 13.2 1区 材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY Pub Date : 2024-08-26 DOI: 10.1016/j.nantod.2024.102467
Yipeng Li , Jiacheng Ren , Ziqi Cao , Shangquan Zhao , Zhong-Qun Tian , Xiaoyong Wu , Guang Ran

Although CrNb coated zirconium alloy materials are considered as ATF candidates with excellent oxidation resistance and mechanical properties, the irradiation response behavior under harsh and complex service conditions is still unrevealed. Here, we report the evolution of the microstructure of pure Cr and CrNb coatings with different Nb contents under simultaneous irradiation with Cr+-He+-H2+ triple ion beams at 633 K by using an advanced in-situ transmission electron microscope (TEM). The results show that CrNb coatings with high Nb content have better irradiation stability. Under high-temperature irradiation conditions, irradiation-induced oxidation and grain growth or crystallization are observed for both Cr-8 Nb with a nanocrystalline structure and Cr-18 Nb coatings with an almost amorphous structure, whereas Cr-37 Nb coatings maintains relatively intact in the amorphous phase after irradiation at a dose of 10 dpa. Based on the in-situ tracking of the microstructural evolution, it is revealed that the mechanism of irradiation-accelerated oxidation and crystallization of coatings originates from displacement cascades enhancing local atomic diffusion and rearrangement.

尽管铬铌涂层锆合金材料被认为是具有优异抗氧化性和机械性能的 ATF 候选材料,但其在苛刻和复杂服役条件下的辐照响应行为仍未得到揭示。在此,我们利用先进的原位透射电子显微镜(TEM),报告了纯铬和不同铌含量的铬铌涂层在 633 K 下同时受到 Cr+-He+-H2+ 三重离子束辐照时的微观结构演变。结果表明,铌含量高的铬铌镀层具有更好的辐照稳定性。在高温辐照条件下,具有纳米晶结构的 Cr-8 Nb 和几乎具有无定形结构的 Cr-18 Nb 涂层都能观察到辐照引起的氧化和晶粒生长或结晶,而 Cr-37 Nb 涂层在 10 dpa 剂量辐照后仍能保持相对完整的无定形相。根据对微观结构演变的原位跟踪,可以发现辐照加速涂层氧化和结晶的机理源于位移级联增强了局部原子扩散和重排。
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引用次数: 0
A multichannel nucleic acid-based Ca2+ nanomodulator induces multilevel destruction of mitochondria for cancer therapy 基于核酸的多通道 Ca2+ 纳米调节器可诱导线粒体的多级破坏,用于癌症治疗
IF 13.2 1区 材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY Pub Date : 2024-08-26 DOI: 10.1016/j.nantod.2024.102465
Weifang Gong , Tingting Zhao , He Yuan , Geng Yang , Weicai Wang , Xuemei Li , Huangxian Ju

Mitochondria play a crucial function in tumor proliferation and apoptosis, and inducing mitochondrial dysfunction in cells has emerged as a promising therapeutic approach for tumors. Here, curcumin (CUR) is enrolled in amorphous calcium phosphate (ACP) through the coprecipitation method, followed by Cy5.5-labeled DNA was adsorbed on its surface to propose an acidity-responsive nucleic acid-based nanomodulator (ACP@C-D) to enhance Ca2+ overload and mitochondrial biomineralization for cancer therapy by amplifying intra-mitochondrial Ca2+ concentration. After tumor cell administration, the ACP@C-D will disintegrate in the acidic environment to enhance Ca2+ overload by the combined interaction of a dramatic increase in Ca2+ concentration and Ca2+ efflux inhibition by Cur. Moreover, the mitochondrial targeting ability of Cy5.5 allows DNA enrichment at mitochondrial, and the phosphate on DNA provides reaction sites for Ca2+ to achieve mitochondrial biomineralization thus mitochondrial dysfunction, which is reported for the first time. The facile and functional strategy of the nanomodulator will provide new insights into inmitochondria-based cancer therapy.

线粒体在肿瘤增殖和凋亡过程中发挥着重要功能,诱导细胞线粒体功能障碍已成为一种很有前景的肿瘤治疗方法。本文通过共沉淀法将姜黄素(CUR)加入到无定形磷酸钙(ACP)中,然后在其表面吸附Cy5.5标记的DNA,提出了一种基于酸性响应核酸的纳米调节剂(ACP@C-D),通过放大线粒体内的Ca2+浓度来增强Ca2+过载和线粒体生物矿化,从而达到治疗肿瘤的目的。肿瘤细胞给药后,ACP@C-D 会在酸性环境中崩解,在 Ca2+ 浓度急剧增加和 Cur 抑制 Ca2+ 外流的共同作用下,增强 Ca2+ 过载。此外,Cy5.5 的线粒体靶向能力可使 DNA 富集于线粒体,DNA 上的磷酸为 Ca2+ 提供反应位点,实现线粒体生物矿化,从而导致线粒体功能障碍,这是首次报道。纳米调节剂的简便和功能性策略将为基于线粒体的癌症治疗提供新的见解。
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引用次数: 0
Apoptotic cell mimics enhance immunogenic cell death and inflame tumor microenvironment by modulating macrophages 凋亡细胞模拟物通过调节巨噬细胞增强免疫原性细胞死亡并使肿瘤微环境恶化
IF 13.2 1区 材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY Pub Date : 2024-08-24 DOI: 10.1016/j.nantod.2024.102464
Jing-Yun Su , Wen-Hao Li , Tian-Yang Wang , Shao-Hua Zhuo , Lang Zhao , Yan-Mei Li

Macrophages play a crucial role in regulating the efficacy of immunotherapy. However, the tumor microenvironment (TME) educated macrophages into immune-suppressive phenotypes. The suppressive effects are largely caused through the clearance of apoptotic cells and secretion of anti-inflammatory cytokines. Here, we propose that apoptotic cell-mimicking liposomes (PSx) that contain phosphatidylserine reduce the phagocytosis of apoptotic tumor cells by interacting with various phosphatidylserine-recognizing phagocytotic receptors on macrophages. Uncleared apoptotic tumor cells undergo secondary necrosis, leading to the abundant release of tumor antigens and immunostimulants, thus causing immunogenic cell death (ICD). TLR7/8 agonists are further loaded as model agonists in liposomes (R@PSx) to reverse the suppressive tumor microenvironment. These apoptotic cell mimics successfully induce a cytotoxic T-cell response and lead to tumor regression in different tumor models. This work provides a novel strategy to enhance the therapeutic effect of ICD and inflame the TME by modulating the function of macrophages.

巨噬细胞在调节免疫疗法疗效方面发挥着至关重要的作用。然而,肿瘤微环境(TME)会将巨噬细胞教育成免疫抑制表型。这种抑制作用主要是通过清除凋亡细胞和分泌抗炎细胞因子产生的。在这里,我们提出,含有磷脂酰丝氨酸的仿凋亡细胞脂质体(PSx)通过与巨噬细胞上的各种磷脂酰丝氨酸识别吞噬受体相互作用,减少对凋亡肿瘤细胞的吞噬。未被清除的凋亡肿瘤细胞会发生继发性坏死,导致肿瘤抗原和免疫刺激物质的大量释放,从而引起免疫原性细胞死亡(ICD)。TLR7/8 激动剂作为模型激动剂进一步装载在脂质体(R@PSx)中,以逆转抑制性肿瘤微环境。这些凋亡细胞模拟物成功诱导了细胞毒性 T 细胞反应,并导致不同肿瘤模型中的肿瘤消退。这项工作提供了一种新的策略,通过调节巨噬细胞的功能来增强 ICD 的治疗效果并使 TME 发炎。
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引用次数: 0
Optimizing structural design in SN38 delivery: More assembly stability and activation efficiency 优化 SN38 输送的结构设计:更高的装配稳定性和激活效率
IF 13.2 1区 材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY Pub Date : 2024-08-23 DOI: 10.1016/j.nantod.2024.102450
Yaqiao Li , Lingxiao Li , Yanzhong Hao , Jingxuan Zhang , Cuiyun Liu , Erwei Zhao , XianBao Shi , Xiaohui Pu , Jin Sun , Zhonggui He , Bingjun Sun

Dimeric prodrug self-assembly nanoparticles (DPS NPs) present promising avenues for chemotherapeutic delivery, yet optimizing the linker design for effective SN38 delivery remains challenging. We developed various SN38 dimeric prodrugs with differing linker lengths to explore how linker length impacts DPS NP performance. Our study reveals that linker length critically affects the nanoparticles assembly stability and activation efficiency. Specifically, too short linkers compromise assembly stability and lead to premature drug activation in the bloodstream, raising safety concerns. Conversely, too long linkers hinder both assembly stability and activation efficiency within tumor cells, diminishing anti-tumor effectiveness. The optimal linker (C12) achieved the best balance, ensuring robust assembly stability and high activation efficiency, thereby enhancing anti-tumor efficacy while maintaining a favorable safety profile. This work underscores the significance of linker length in designing effective DPS NPs for cancer treatment.

二聚原药自组装纳米粒子(DPS NPs)为化疗药物的递送提供了前景广阔的途径,然而优化连接体设计以实现有效的 SN38 递送仍然具有挑战性。我们开发了各种具有不同连接体长度的 SN38 二聚体原药,以探索连接体长度如何影响 DPS NP 的性能。我们的研究发现,连接体长度对纳米粒子的组装稳定性和活化效率有着至关重要的影响。具体来说,过短的连接体会影响组装稳定性,导致药物在血液中过早活化,从而引发安全问题。相反,过长的连接体则会阻碍组装稳定性和在肿瘤细胞内的激活效率,从而降低抗肿瘤效果。最佳连接体(C12)实现了最佳平衡,确保了强大的组装稳定性和较高的激活效率,从而在提高抗肿瘤疗效的同时保持了良好的安全性。这项工作强调了连接子长度在设计有效的 DPS NPs 用于癌症治疗中的重要性。
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引用次数: 0
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