Biomacromolecules最新文献_第9页

Cellulose-Refined Cholesteric Liquid Crystal Films with Both Right- and Left-Handed Circularly Polarized Light Reflection 具有左、右圆偏振光反射的纤维素精制胆甾液晶膜。

IF 5.4 2区化学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biomacromolecules

Pub Date : 2026-01-12 DOI: 10.1021/acs.biomac.5c01286

Yu Sotoyama, Yuki Ogiwara, Kazuma Matsumoto, Koya Sunagawa, Naoto Iwata, Seiichi Furumi

Biomass-refinery enables sustainable production of viable fuels and materials. Cellulose has garnered significant attention as the most earth-abundant renewable polymer. Hydroxypropyl cellulose (HPC) derivatives are known to self-organize cholesteric liquid crystal (CLC) mesophase with right-handed macromolecular sense, leading to the chiroptical effect of right-handed circularly polarized light (CPL) reflection. In this report, we establish a promising strategy to prepare solid-state CLC films with both right- and left-handed CPL reflection by shearing chemically modified cellulose derivatives. A key piece of equipment is the rheometer with precisely tunable shear conditions. Both-handed CPL reflection arises from shear-induced enhancement in optical retardation over 300 nm by distorting helical molecular assemblages, as confirmed with the Sénarmont method. The polarization state of incident light is altered within the film thickness direction. Moreover, we successfully fabricate intriguing CLC films with both-handed CPL reflection using inherently right-handed CLCs of the HPC derivative and also inherently left-handed CLCs of the ethyl cellulose derivative.

生物质精炼厂能够可持续地生产可行的燃料和材料。纤维素作为地球上最丰富的可再生聚合物已经引起了极大的关注。羟丙基纤维素（HPC）衍生物具有自组织具有右旋大分子意义的胆甾液晶（CLC）中间相，导致右旋圆偏振光（CPL）反射的chiroptic效应。在本报告中，我们建立了一种有前途的策略，通过剪切化学修饰的纤维素衍生物来制备具有右手和左手CPL反射的固态CLC薄膜。一个关键的设备是具有精确可调剪切条件的流变仪。双手CPL反射是由剪切引起的300 nm以上的光学延迟增强引起的，通过扭曲螺旋分子组合，ssamarmont方法证实了这一点。入射光的偏振态在膜厚方向上发生改变。此外，我们成功地利用HPC衍生物的固有右手CLCs和乙基纤维素衍生物的固有左手CLCs制备了具有双手CPL反射的CLC薄膜。

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引用次数: 0

Genetic Factors Affecting the Quality of Recombinant Therapeutic Proteins in CHO Cells 影响CHO细胞中重组治疗蛋白质量的遗传因素。

IF 5.4 2区化学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biomacromolecules

Pub Date : 2026-01-12 DOI: 10.1021/acs.biomac.5c01454

Chun-Liu Mi , Shao-Lei Geng , Jing-Wen Xue , Qiu-Li Sun , Wei-Hua Dong , Ji-Hong Zhang , Qin Li , Xiao-Yin Wang , Tian-Yun Wang

Recombinant therapeutic proteins (RTPs) are widely used to treat various major diseases. Chinese hamster ovary (CHO) cells are the preferred mammalian cell expression system for the production of RTPs. However, maintaining high productivity while ensuring good-quality RTPs is still challenging. Glycosylation, aggregation, charge variants, and degradation are the main quality attributes of RTPs and can impact their safety, biological activity, stability, and half-life. Modifications of associated genetic factors have been performed to improve the quality of the RTPs. For example, knocking out the α-1,6-fucosyltransferase (FUT8) gene results in the production of fucose-free antibodies, significantly enhancing antibody-dependent cellular cytotoxicity (ADCC). Overexpressing the molecular chaperone GRP78 reduces antibody aggregation rates while improving cell survival rates. Knocking out the carboxypeptidase D (CpD) gene completely eliminates C-terminal lysine heterogeneity, thereby improving the antibody charge uniformity. The deletion of the insulin-degrading enzyme (IDE) gene nearly eliminates insulin degradation. Understanding the genetic factors that influence the quality of therapeutic proteins during CHO cell culture is essential for the production of high-quality therapeutic proteins. This review summarizes the genetic factors contributing to RTP heterogeneity in CHO cells and discusses innovative strategies to address this heterogeneity, such as CRISPR/Cas9-mediated gene knockout, synergistic glycosyltransferase overexpression, and host cell engineering.

重组治疗蛋白（rtp）被广泛用于治疗各种重大疾病。中国仓鼠卵巢（CHO）细胞是产生rtp的首选哺乳动物细胞表达系统。然而，在确保高质量rtp的同时保持高生产率仍然具有挑战性。糖基化、聚集、电荷变异和降解是rtp的主要质量属性，可以影响它们的安全性、生物活性、稳定性和半衰期。已经对相关遗传因素进行了修改，以提高rtp的质量。例如，敲除α-1,6-聚焦转移酶（FUT8）基因会产生无聚焦抗体，显著增强抗体依赖性细胞毒性（ADCC）。过表达分子伴侣GRP78可降低抗体聚集率，同时提高细胞存活率。敲除羧基肽酶D （CpD）基因完全消除了c端赖氨酸的异质性，从而提高了抗体的电荷均匀性。胰岛素降解酶（IDE）基因的缺失几乎消除了胰岛素的降解。了解在CHO细胞培养过程中影响治疗蛋白质量的遗传因素对于生产高质量的治疗蛋白至关重要。本文总结了CHO细胞中RTP异质性的遗传因素，并讨论了解决这种异质性的创新策略，如CRISPR/ cas9介导的基因敲除、协同糖基转移酶过表达和宿主细胞工程。

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引用次数: 0

Peptidyl Biomimetic Adhesives via Sequential Isomerism-Dictated Physical Condensation and Underwater Adhesion 肽基仿生胶粘剂的顺序异构物理缩聚和水下粘附。

IF 5.4 2区化学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biomacromolecules

Pub Date : 2026-01-12 DOI: 10.1021/acs.biomac.5c02137

Chenhao Ji, Xinyan Wang, Guang Wen, He Zhao, Xiangyi Li, Wen Li

Physical condensation of oligopeptides provides a reductionist platform for probing the underwater adhesion of marine adhesive proteins. The link between peptide sequence and adhesion remains unclear at the molecular level. Using cationic peptide isomers and anionic H₄SiW₁₂O₄₀ (SiW) clusters, we explored how sequence isomerism governs the adhesion of the peptide/SiW condensates via regulating the layout of two lysine residues within the peptide isomers. On stainless steel (SS), one-end-on isomers with lysine residues at one terminal exhibited adhesion strengths of 43.1–54.2 kPa; end-side-on isomers with lysine residues at both terminals and midsite yielded adhesion of 64.1–67.8 kPa; while double-end-on isomers with lysine residues at both termini achieved adhesion strength of 74.4–87.1 kPa. Furthermore, introducing one glutamic acid residue enables protonation-/deprotonation-driven charge redistribution and adhesion regulation. This work establishes a design principle, whereby the adhesion of peptide condensates can be controlled by optimizing binding site arrangements in peptide sequences.

寡肽的物理缩聚为探索海洋黏附蛋白的水下黏附提供了还原论平台。在分子水平上，肽序列与粘附之间的联系尚不清楚。利用阳离子多肽异构体和阴离子H4SiW12O40 （SiW）簇，我们探索了序列异构体如何通过调节多肽异构体内两个赖氨酸残基的布局来控制多肽/SiW凝聚体的粘附。在不锈钢（SS）上，一端有赖氨酸残基的单端对映异构体的粘附强度为43.1 ~ 54.2 kPa；末端和中间都有赖氨酸残基的端对端异构体的粘附力为64.1 ~ 67.8 kPa；而两端都有赖氨酸残基的双端异构体的粘附强度为74.4-87.1 kPa。此外，引入一个谷氨酸残基可以实现质子化/去质子化驱动的电荷再分配和粘附调节。这项工作建立了一个设计原则，即肽凝聚物的粘附可以通过优化肽序列中的结合位点排列来控制。

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引用次数: 0

Simple Hydrophobic Modification of bPEI Confers Potent, STING-Dependent Innate Immunostimulatory Activity 简单的疏水修饰bPEI具有强效的sting依赖性先天免疫刺激活性。

IF 5.4 2区化学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biomacromolecules

Pub Date : 2026-01-12 DOI: 10.1021/acs.biomac.5c01869

Aolin Sun , Liping Liu , Zichao Huang , Yaxin Zhang , Zhenyi Zhu , Jiangai Long , Ziyue An , Yibo Wang , Yusong Cao , Dianwei Wang , Wantong Song

Macromolecular agonists are promising immunomodulators due to multivalency and tunable architectures. Previously, we showed that branched polyethylenimine (bPEI) conjugated with nitrogen-containing heterocycles activates the STING pathway, with branching being pivotal. Here we ask whether nitrogen is indispensable. We synthesized a library of bPEI conjugates bearing non-nitrogenous ligands (heterocycles, nonheterocycles, and aliphatic chains). While bPEI or ligands alone were inactive, >60% of conjugates induced robust IFN-β secretion across multiple cell types. Representative conjugates promoted STING clustering and TBK1/IRF3 phosphorylation, and genetic ablation of STING or cGAS markedly reduced IFN-β induction. Conjugation mitigated PEI cytotoxicity and minimized NF-κB–driven pro-inflammatory cytokines. Docking, log P analysis, and time-resolved uptake profiling established a physicochemical structure–activity relationship linking ligand rigidity, aromaticity, and hydrophobicity to STING binding, internalization, and IFN-β induction. Thus, nitrogen is not essential; simple hydrophobic modifications suffice within a macromolecular scaffold.

由于具有多价性和可调结构，大分子激动剂是很有前途的免疫调节剂。先前，我们发现含氮杂环偶联的支化聚乙烯亚胺（bPEI）激活STING通路，支化是关键。这里我们要问氮是否不可或缺。我们合成了一个含非氮配体（杂环、非杂环和脂肪链）的bPEI偶联物库。虽然bPEI或配体单独无活性，但bb60 %的偶联物诱导多种细胞类型的IFN-β分泌强劲。代表性的偶联物促进了STING的聚集和TBK1/IRF3的磷酸化，STING或cGAS的基因消融显著降低了IFN-β的诱导。偶联可减轻PEI的细胞毒性，减少NF-κ b驱动的促炎细胞因子。对接、log P分析和时间分辨摄取分析建立了配体刚性、芳香性和疏水性与STING结合、内化和IFN-β诱导之间的理化构效关系。因此，氮不是必需的；简单的疏水修饰在大分子支架内就足够了。

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引用次数: 0

Construction of Novel Polylysine/Sodium Alginate Nanocarriers Combining Chlorogenic Acid and siRNA against Keloids 结合绿原酸和siRNA的聚赖氨酸/海藻酸钠抗瘢痕疙瘩纳米载体的构建

IF 5.4 2区化学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biomacromolecules

Pub Date : 2026-01-12 DOI: 10.1021/acs.biomac.5c00989

Ruiying Zhang , Hanfeng Li , Tong Zhang , Bing Zhang , Yihu Wang , Yanchuan Guo

Addressing the underappreciated critical role of angiogenesis and immune dysregulation in keloid formation, we developed a novel nanocarrier (PCS) based on a dual network of physical cross-linking for the efficient release of siTGF-β1 and chlorogenic acid. PCS was self-assembled from polyethylenimine/siTGF-β1 and chlorogenic acid-embedded polylysine/sodium alginate. The results demonstrated that PCS could inhibit the proliferation, induce apoptosis of human umbilical vein endothelial cells and human keloid fibroblasts by regulating their cell cycle, and improve the immune microenvironment at the lesion. By transcriptomics and network pharmacology analysis, PCS inhibited keloid development mainly through the TGF-β1/EGR1 signaling pathway. The final results of animal experiments also proved that the material exerted a favorable effect in keloid treatment. Overall, PCS, as a novel nanocarrier combining siRNA-based gene therapy with chlorogenic acid, was a promising approach for the treatment of keloids.

为了解决血管生成和免疫失调在瘢痕疙瘩形成中被低估的关键作用，我们开发了一种基于物理交联双重网络的新型纳米载体（PCS），用于有效释放siTGF-β1和绿原酸。PCS由聚乙烯亚胺/siTGF-β1和绿原酸包埋的聚赖氨酸/海藻酸钠自组装而成。结果表明，PCS可通过调节人脐静脉内皮细胞和瘢痕疙瘩成纤维细胞的细胞周期，抑制其增殖，诱导其凋亡，改善病变处的免疫微环境。通过转录组学和网络药理学分析，PCS主要通过TGF-β1/EGR1信号通路抑制瘢痕疙瘩的发展。动物实验的最终结果也证明了该材料对瘢痕疙瘩的治疗有良好的效果。综上所述，PCS作为一种新型的纳米载体，将sirna基因疗法与绿原酸相结合，是治疗瘢痕疙瘩的一种很有前景的方法。

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引用次数: 0

Bacteria-Induced Oligopeptide Assembly Enables Effective Bacterial Killing with Low Cytotoxicity and Hemolysis 细菌诱导的寡肽组装使低细胞毒性和溶血有效杀死细菌。

IF 5.4 2区化学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biomacromolecules

Pub Date : 2026-01-12 DOI: 10.1021/acs.biomac.5c01737

Yi Cheng, He Zhao, Jiayi Sun, Shuaishuai Nie, Wen Li

Bacteria-induced on-membrane assembly of oligopeptides showed the potential for balancing their persistent conflict between antibacterial activity and biocompatibility. However, molecular determinants linking the peptide sequence, assembly behavior, antibacterial efficacy, and biocompatibility remain insufficiently understood. Here, we investigated a series of heptapeptides, (RX)₃R (X = A, I, F), and demonstrated the significant influence of hydrophobic residues on bacteria-induced assembly, antibacterial performance, cytotoxicity, and hemolytic activity. Negatively charged liposomes or bacterial membranes could induce the assembly of (RI)₃R and (RF)₃R into nanofibers, which in turn exhibited enhanced antibacterial efficacy against Gram-negative Escherichia coli with minimum inhibitory concentrations (MICs) of 60 μM but poor antibacterial activity on Gram-positive Staphylococcus aureus (MICs: 400–500 μM). Importantly, both peptides demonstrated excellent biocompatibility, with cytotoxicity thresholds of 600 μM (RI)₃R and 2000 μM (RF)₃R and hemolysis thresholds up to 2000 and 4000 μM, respectively. These findings provide valuable insights for the rational design of antibacterial oligopeptides.

细菌诱导的寡肽在膜上组装显示出平衡其抗菌活性和生物相容性之间持续冲突的潜力。然而，连接肽序列、组装行为、抗菌功效和生物相容性的分子决定因素仍未充分了解。在这里，我们研究了一系列七肽，（RX）3R (X = a， I， F)，并证明了疏水残基对细菌诱导的组装，抗菌性能，细胞毒性和溶血活性的显著影响。带负电荷的脂质体或细菌膜可诱导（RI）3R和（RF）3R组装成纳米纤维，纳米纤维对革兰氏阴性大肠杆菌的抑菌效果较好，最低抑菌浓度（mic）为60 μM，但对革兰氏阳性金黄色葡萄球菌（mic: 400-500 μM）的抑菌活性较差。重要的是，这两种肽均表现出良好的生物相容性，细胞毒性阈值分别为600 μM (RI)3R和2000 μM (RF)3R，溶血阈值分别为2000 μM和4000 μM。这些发现为抗菌寡肽的合理设计提供了有价值的见解。

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引用次数: 0

From Amorphous Bundles to Nanoporous Peptide Frameworks: Solvent-Driven Self-Assembly of Pro-Val-Pro-Val 从无定形束到纳米多孔肽框架：溶剂驱动的Pro-Val-Pro-Val自组装。

IF 5.4 2区化学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biomacromolecules

Pub Date : 2026-01-12 DOI: 10.1021/acs.biomac.5c01800

Kacper Drużbicki , Piotr Paluch , Rafał Dolot , Irena Bąk-Sypień , Ewelina Kuc , Agata Jeziorna , Marek J. Potrzebowski

Peptides are ubiquitous and functionally diverse biomolecules with a strong propensity to form noncovalent nanostructures of unexpected complexity. Using nuclear magnetic resonance (NMR), X-ray diffraction, and computational modeling, we show that the amphiphilic tetrapeptide l-prolyl-l-valyl-l-prolyl-l-valine (PVPV) undergoes solvent-directed self-assembly into two molecular frameworks, each built upon a helical motif formed through charge-assisted hydrogen bonding. Water–methanol crystallization yields a solvent-stabilized porous tetragonal framework, whereas pure water produces either a low-hydration amorphous phase or a dense, disordered triclinic form. These behaviors challenge first-principles modeling and expose limitations of static semilocal density functional theory. Calculations indicate that the porous framework is energetically less favorable, highlighting the importance of water disorder and conformational flexibility in forming metastable structures. The low-hydration phase exhibits intrinsic conformational disorder, motivating an in-depth investigation via NMR crystallography. Advanced solid-state NMR on isotopically labeled samples provides assignments not achievable through conventional approaches, revealing subtle molecular distortions that modulate local ordering.

肽是一种普遍存在且功能多样的生物分子，具有形成非共价纳米结构的强烈倾向，具有意想不到的复杂性。利用核磁共振（NMR）、x射线衍射和计算模型，我们发现两亲性四肽l-丙氨酸-l-丙氨酸-l-丙氨酸-l-丙氨酸-l-丙氨酸-l-缬氨酸（PVPV）经历了溶剂定向自组装成两个分子框架，每个分子框架都建立在通过电荷辅助氢键形成的螺旋基序上。水-甲醇结晶产生溶剂稳定的多孔四边形框架，而纯水产生低水化无定形相或致密，无序的三斜形式。这些行为挑战了第一性原理建模，暴露了静态半局部密度泛函理论的局限性。计算表明，多孔框架在能量上不太有利，突出了水无序性和构象柔韧性在形成亚稳结构中的重要性。低水化相表现出固有的构象紊乱，激发了通过核磁共振晶体学的深入研究。在同位素标记的样品上，先进的固态核磁共振提供了传统方法无法实现的分配，揭示了调节局部排序的微妙分子扭曲。

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引用次数: 0

Unravelling the Complexity of LignosulfonatesFractionation and Physicochemical Profiling 揭示木质素磺酸盐的复杂性──分馏和物理化学分析。

IF 5.4 2区化学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biomacromolecules

Pub Date : 2026-01-12 DOI: 10.1021/acs.biomac.5c02229

Veslemøy Margrethe Selvik , Finn Lillelund Aachmann , Carlos Salas-Bringas , Vebjørn Eikemo

Understanding the structural architecture of lignosulfonates is essential for optimizing their performance and enabling targeted modifications for sustainable applications. This study investigates six sodium lignosulfonate fractions (2,200–78,000 g/mol; dispersity 1.7–12.2) obtained via two-step ultrafiltration. Functional group analysis (sulfonation degree, phenolic hydroxyl, and carboxylic acid) using elemental analysis and NMR revealed minimal variation across fractions. Hydrophobic interaction chromatography and intrinsic viscosity measurements showed that increasing molecular weight correlates with reduced charge-to-size ratios and enhanced hydrophobicity. Rheological data showed that high-molecular-weight fractions exhibit greater conformational changes and compaction under high ionic strength. 2D NMR of purified fractions uncovered new structural features, including guaiacylethanol and fully characterized mono- and disulfonated bonding patterns. These findings advance the structural mapping of lignosulfonates and demonstrate that molecular weight is the dominant factor influencing the physical properties. The study highlights the value of combining fractionation, rheology, and NMR techniques to deepen our understanding of lignosulfonate structure and guide future lignin-based materials applications.

了解木质素磺酸盐的结构结构对于优化其性能和实现可持续应用的针对性修改至关重要。研究了两步超滤得到的6个木质素磺酸钠馏分（2200 ~ 78000 g/mol，分散度1.7 ~ 12.2）。使用元素分析和核磁共振的官能团分析（磺化程度、酚羟基和羧酸）显示各馏分之间的变化最小。疏水相互作用色谱和特性粘度测量表明，分子量的增加与电荷尺寸比的降低和疏水性的增强有关。流变学数据表明，高分子量组分在高离子强度下表现出更大的构象变化和压实。纯化馏分的二维核磁共振揭示了新的结构特征，包括愈创木基乙醇和完全表征的单磺酸和二磺酸键模式。这些发现促进了木质素磺酸盐的结构作图，并证明分子量是影响其物理性质的主要因素。该研究强调了将分选、流变学和核磁共振技术相结合的价值，以加深我们对木质素磺酸盐结构的理解，并指导未来木质素基材料的应用。

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引用次数: 0

GSH-Responsive Prodrug Polymersomes for Copper-Free Cuproptosis and Synergistic Photothermal Cancer Therapy gsh反应性前药聚合体用于无铜铜增生和协同光热癌症治疗。

IF 5.4 2区化学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biomacromolecules

Pub Date : 2026-01-12 DOI: 10.1021/acs.biomac.5c01893

Fangrong Tan, Yuandong Zeng, Donghua Dong, Yan Deng, Zhe Tang, LinGe Wang, Qianqian Yu

Cuproptosis offers a promising alternative to apoptosis-based cancer therapies but faces challenges, such as poor tumor drug accumulation, rapid clearance of copper ionophores, and high intracellular glutathione (GSH). Herein, we developed a GSH-responsive prodrug polymersome (PED@ICG) for copper-independent cuproptosis and synergistic photothermal therapy. Diethyldithiocarbamate (DTC) was covalently attached via disulfide bonds, ensuring a GSH-triggered release and intracellular GSH depletion. The amphiphilic polyprodrug formed stable polymersomes, and ICG coloading endowed imaging ability and NIR-activated photothermal heating. PED@ICG exhibited efficient cellular uptake through dynamin-mediated endocytosis, achieved deep tumor penetration, and selectively released DTC within the reductive tumor microenvironment. In vitro and in vivo studies demonstrated potent anticancer efficacy without the need for exogenous copper, while NIR irradiation further enhanced therapeutic outcomes through localized hyperthermia. This work offers a promising strategy for precise cuproptosis modulation and photothermal synergism, providing a clinically translatable nanoplatform for copper-independent tumor therapy.

铜细胞凋亡是基于细胞凋亡的癌症治疗的一个有希望的替代方案，但面临着挑战，如肿瘤药物积累差，铜离子载体的快速清除和高细胞内谷胱甘肽（GSH）。在此，我们开发了一种gsh反应性前药聚合体（PED@ICG），用于不依赖铜的铜还原和协同光热治疗。二乙基二硫代氨基甲酸酯（DTC）通过二硫键共价连接，确保GSH触发的释放和细胞内GSH消耗。两亲性聚前药形成稳定的聚合体，ICG负载赋予成像能力和nir激活的光热加热。PED@ICG通过动力蛋白介导的内吞作用表现出有效的细胞摄取，实现了肿瘤深度渗透，并在还原性肿瘤微环境中选择性释放DTC。体外和体内研究表明，不需要外源性铜就能有效地抗癌，而近红外照射通过局部热疗进一步提高了治疗效果。这项工作提供了一种有前景的策略，用于精确的铜生长调节和光热协同作用，为不依赖铜的肿瘤治疗提供了临床可翻译的纳米平台。

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引用次数: 0

Redox-Responsive Polyurethane Nanonetworks with Tunable Cross-linking: A Robust Platform for Cocktail Chemotherapy 具有可调交联的氧化还原反应聚氨酯纳米网络：鸡尾酒化疗的强大平台。

IF 5.4 2区化学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biomacromolecules

Pub Date : 2026-01-12 DOI: 10.1021/acs.biomac.5c01180

Soumya Kolay , Madhuchhanda Das , Sananda Dey , Tanushree Mondal , Arun Mondal , Subhadeep Kar , Arunima Sengupta , Subhash Haldar , Biplab Giri , Mijanur Rahaman Molla

We formulated a nanonetwork of an amphiphilic polyurethane integrated with a tertiary amine group on the backbone and a pyridyl disulfide group as a pendant. The disulfide linkages within the nanonetwork undergo reductive cleavage in the intracellular redox environment of cancer cells, enabling sustained and site-specific drug release. The positive surface-charge generation under tumor extracellular matrix-like mildly acidic conditions promotes selective uptake of the nanonetwork by cancer cells while minimizing interaction with normal cells, as shown by flow cytometry analysis. Biological evaluation confirmed selective internalization and potent cytotoxicity in HeLa and MDA-MB-231 cells following treatment with NN@DOX, while normal cells were effectively shielded from off-target toxicity. Furthermore, the dual-drug-loaded nanonetwork (NN@DOX-CPT) exhibited superior therapeutic outcomes, as demonstrated by a significantly lower IC₅₀ (3.98 μg/mL) value compared to single-drug formulations, NN@DOX (IC₅₀ = 9.89 μg/mL), confirming a combined effect. Overall, this polymeric nanonetwork could be a promising system for combination drug-based targeted chemotherapy.

我们配制了一种两亲性聚氨酯的纳米网络，在主链上集成了叔胺基团和吡啶二硫化基作为垂坠。纳米网络中的二硫键在癌细胞的细胞内氧化还原环境中进行还原性裂解，从而实现持续和位点特异性的药物释放。流式细胞术分析显示，在肿瘤细胞外基质样的温和酸性条件下，正表面电荷的产生促进了癌细胞对纳米网络的选择性摄取，同时最大限度地减少了与正常细胞的相互作用。生物学评价证实了NN@DOX治疗后HeLa和MDA-MB-231细胞的选择性内化和强大的细胞毒性，而正常细胞有效地屏蔽了脱靶毒性。此外，双药负载纳米网络（NN@DOX-CPT）表现出更好的治疗效果，其IC50值（3.98 μg/mL）显著低于单药配方NN@DOX (IC50 = 9.89 μg/mL)，证实了联合效应。总的来说，这种聚合物纳米网络可能是一种很有前途的基于联合药物的靶向化疗系统。

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引用次数: 0