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Nanochaperones Based on Hydrophobic Interaction and Coordination Inhibit Protein Misfolding and Fibrillation

Chinese Journal of Polymer Science 2024年第11期42卷 1710-1718,I0009页

作者： Hui Wang Lin-Lin Xu Lin-Qi Shi ru-jiang ma Key Laboratory of Functional Polymer materials of Ministry of Education Institute of Polymer ChemistryState Key Laboratory of Medicinal Chemical BiologyFrontiers Science Center for New Organic MatterCollege of ChemistryNankai UniversityTianjin300071China Haihe Laboratory of Sustainable Chemical Transformations Tianjin300192China

Amyloidosis is characterized by the deposition of fibrillar aggregates,with a specific peptide or protein as the primary component,in affected tissues or *** proliferation and deposition of amyloid fibrils can cause organismal dysfunction and lethal pathological outcomes associated with *** this study,a nanochaperone(nChap-NA)was developed to inhibit protein misfolding and fibrillation by simulating the function of natural molecular *** nanochaperone was prepared by self-assembly of two block copolymers PEG-b-PCL and PCL-b-P(NIPAM-co-AANTA),which had a phase-separated surface consisting of hydrophobic PNIPAM microdomains with coordinative NTA(Zn)moieties and hydrophilic PEG *** hydrophobic interaction of the PNIPAM microdomain and the coordination of NTA(Zn)synergistically work together to effectively trap the amyloid monomer and block its fibrillation *** and human islet amyloid polypeptide(hIAPP)were used as model proteins to investigate the nanochaperone's inhibition of amyloid misfolding and *** was proved that the nanochaperone could stabilize the natural conformation of the trapped insulin and hIAPP,and effectively inhibit their *** vivo study demonstrated that the nanochaperone could effectively preserve the bioactivity of insulin and reduce the cytotoxicity caused by hIAPP *** study may provide a promising strategy for the prophylactic treatment of amyloidosis.

关键词： Nanochaperone Amyloidosis Insulin hIAPP Inhibit fibrillation

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A Dynamic Covalent Bonding-based Nanoplatform for Intracellular Co-Delivery of Protein Drugs and Chemotherapeutics with Enhanced Anti-Cancer Effect

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Chinese Journal of Polymer Science 2024年第5期42卷 559-569,I0005页

作者： Sai-Nan Liu Jia-Hui Meng Li-Yun Cui Hua Chen Lin-Qi Shi ru-jiang ma Key Laboratory of Functional Polymer materials of Ministry of Education Institute of Polymer ChemistryTianjin Key Laboratory of Functional Polymer MaterialsState Key Laboratory of Medicinal Chemical BiologyFrontiers Science Center for New Organic MatterCollege of ChemistryNankai UniversityTianjin300071China Haihe Laboratory of Sustainable Chemical Transformations Tianjin300192China

Efficient intracellular delivery of protein drugs is critical for protein *** combination of protein drugs with chemotherapeutics represents a promising strategy in enhancing anti-cancer ***,co-delivery systems for efficient delivery of these two kinds of drugs are still lacking because of their different ***,we show a well-designed delivery system based on dynamic covalent bond for efficient intracellular co-delivery of ribonuclease A(RNase A)and doxorubicin(DOX).Two polymers,PEG-b-P(Asp-co-AspDA)and PAE-b-P(Asp-co-AspPBA),and two 2-acetylphenylboronic acid(2-APBA)-functionalized drugs,2-APBA-RNase A and 2-APBA-DOX,self-assemble into mixed-shell nanoparticles(RNase A/DOX@MNPs)via dynamic phenylboronic acid(PBA)-catechol bond between PBA and dopamine(DA)*** PBA-catechol bond endows the nanoparticles with high stability and excellent stimulus-responsive drug release *** the slight acidic environment at tumor tissue,RNase A/DOX@MNPs are positively charged,promoting their *** cellular uptake into endosome,further protonation of PAE chains leads to the rupture of endosomes because of the proton sponge effect and the cleavage of PBA-catechol bond promotes the release of two *** cytoplasm,the high level of GSH removed the modification of 2-APBA on *** restored RNase A and DOX show a synergistic and enhanced antic-cancer *** system may be a promising platform for intracellular co-delivery of protein drugs and chemotherapeutics.

关键词： Drug co-delivery Combination therapy Dynamic covalent bond

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Bioinspired Self-assembly Nanochaperone Inhibits Tau-Derived PHF6 Peptide Aggregation in Alzheimer’s Disease

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Chinese Journal of Polymer Science 2022年第9期40卷 1062-1070页

作者： Lin Zhu Ming-Qing Zhang Hao-Ren Jing Xi-Peng Zhang Lin-Lin Xu ru-jiang ma Fan Huang Lin-Qi Shi State Key Laboratory of Medicinal Chemical Biology Key Laboratory of Functional Polymer Materials of Ministry of EducationCollege of ChemistryNankai UniversityTianjin 300071China Key Laboratory of Radiopharmacokinetics for Innovative Drugs Chinese Academy of Medical Sciencesand Institute of Radiation MedicineChinese Academy of Medical Sciences&Peking Union Medical CollegeTianjin300192China Nankai University School ofMedicine Nankai UniversityTianjinChina Department of Colorectal SurgeryTianjin Union Medical CenterTianjin 300074 China Department of Colorectal Surgery Tianjin Union Medical CenterTianjin 300121China

After repeated frustrations with amyloid beta(Aβ)-targeted clinical trials for Alzheimer’s disease(AD)in recent years,the therapeutic focus of AD has gradually shifted from Aβto tau *** misfolding and aggregation of tau protein into neurofibrillary tangles(NFTs)cause neuron death and synaptic dysfunction,and the deposition of NFTs is more closely related to the severity of AD than Aβ***,it has great potential to target tau protein aggregation for AD *** hexapeptide VQIVYK(known as PHF6)in tau protein has been found to play a dominant role for tau aggregation and was widely used as a model to design tau protein aggregation ***,inspired by natural heat shock protein(HSPs),we fabricated a self-assembly nanochaperone based on mixed-shell polymeric micelle(MSPM)as a novel tau-targeted AD *** tunable phase-separated microdomains on the surface,the nanochaperone could effectively bind with PHF6 aggregates,inhibit PHF6 aggregation,block neuronal internalization of PHF6 species,thus significantly alleviating PHF6 mediated ***,the as-prepared nanochaperone could work with proteinase to facilitate the degradation of PHF6 *** bioinspired nanochaperone demonstrated a new way to target tau protein and provided a promising strategy for AD treatment.

关键词： Alzheimer’s disease Tau protein PHF6 Nanochaperone Inhibition

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pH-responsive Micelles from a Blend of PEG-b-PLA and PLA-b-PDPA Block Copolymers: Core Protection Against Enzymatic Degradation

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Chinese Journal of Polymer Science 2018年第11期36卷 1262-1268页

作者： Yan-Ling Xu Ao-Ting Qu ru-jiang ma Ang Li Zhen-Kun Zhang Zhi-Qiang Shang Yao-Fang Zhang Lu-Xia Bu Ying-Li An State Key Laboratory of Medicinal Chemical Biology Key Laboratory of Functional Polymer Materials of Ministry of Education Institute of Polymer Chemistry Nankai University College of Basic Science Chemistry Experiment Teaching Center Tianjin Agricultural University

pH-responsive micelles with a biodegradable PLA core and a mixed PEG/PDPA shell were prepared by self-assembly of poly（ethylene glycol）-b-poly（lactic acid）（PEG-b-PLA） and poly（2-（diisopropylamino）ethyl methacrylate）-b-poly（lactic acid）（PDPA-b- PLA）. The micellization status with different pH and the enzyme degradation behavior were characterized by IH-NMR spectroscopy, dynamic light scattering measurement and zeta potential test. The pH turning point of PDPA block was determined to be in the range of 5.5-7.0. While the pH was above 7.0, the PDPA block collapsed onto the PLA core and could protect the PLA core from invasion of enzyme, as a result, the micelle exhibited a resistance to the enzymatic degradation.

关键词： pH-responsive Enzymatic degradation Poly(lactic acid)

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基于苯硼酸的葡萄糖响应性聚合物材料在胰岛素投递和血糖检测中的应用

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高分子学报 2014年第9期24卷 1161-1173页

作者：刘赣杨浩马如江史林启功能高分子材料教育部重点实验室南开大学高分子化学研究所天津化学化工协同创新中心天津300071

近年来,葡萄糖响应性聚合物材料因其在糖尿病诊断和治疗领域的潜在应用而被广泛研究.其中基于苯硼酸(PBA)的葡萄糖响应性聚合物作为人工合成材料而具有体系稳定,可逆响应的优势.本文主要从自调节胰岛素投递和血糖持续检测两个方面综述... 详细信息

近年来,葡萄糖响应性聚合物材料因其在糖尿病诊断和治疗领域的潜在应用而被广泛研究.其中基于苯硼酸(PBA)的葡萄糖响应性聚合物作为人工合成材料而具有体系稳定,可逆响应的优势.本文主要从自调节胰岛素投递和血糖持续检测两个方面综述近年来基于苯硼酸体系的聚合物材料的研究进展.自调节胰岛素控制释放体系主要包括葡萄糖响应性微/纳米凝胶、聚合物胶束和囊泡3种形态,它们的形态结构组成对葡萄糖响应性能力,反复开关释放及胰岛素的包覆都有很大的影响.基于苯硼酸体系的血糖持续检测方法主要包括荧光感应器和可视感应器.随着这些聚合物材料性能的逐步完善,它们将更有实际应用的潜力.

关键词：苯硼酸葡萄糖响应性聚合物胰岛素投递血糖检测

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具有可见光响应聚合物纳米粒子的制备及性能研究

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高分子学报 2023年第5期54卷 665-674页

作者：邓飞刘勇马如江马飞贺史林启南开大学化学学院高分子化学研究所天津300071 天津工业大学材料科学与工程学院天津300387 中国科学院大学温州研究院温州325001

利用可见光响应供体-受体Stenhouse加合物(DASAs)设计并制备了2种表面含有可见光响应单元的聚合物纳米粒子,并对纳米粒子的光响应性进行了研究.首先合成了修饰DASA分子的聚合物PGMD,研究结果表明PGMD可溶于与水互溶的有机溶剂(如DMSO)... 详细信息

利用可见光响应供体-受体Stenhouse加合物(DASAs)设计并制备了2种表面含有可见光响应单元的聚合物纳米粒子,并对纳米粒子的光响应性进行了研究.首先合成了修饰DASA分子的聚合物PGMD,研究结果表明PGMD可溶于与水互溶的有机溶剂(如DMSO)中并具有良好的光响应性,PGMD链段可在可见光刺激下响应为亲水状态.因此,含有PGMD链段的嵌段共聚物PCL-b-PGMD可在水中自组装形成胶束,并能与PCL-b-PEG在水中共组装形成复合壳层胶束,但PGMD链段在水中无法可逆响应为疏水状态.为获得具有可逆响应性的聚合物纳米粒子,利用硅烷偶联剂水解修饰的方法得到表面含有疏水三烯状态DASA分子与亲水PEG短链的复合壳层二氧化硅纳米粒子,实验结果表明复合壳层二氧化硅纳米粒子在水环境中有良好的分散稳定性,并且表面修饰的DASA分子仍具有良好的响应性.本研究为设计表面性质可调的响应性聚合物纳米粒子提供了新的设计思路.

关键词：可见光响应复合胶束聚合物纳米粒子供体-受体Stenhouse 加合物

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Ubiquitin-specific protease 1 facilitates tumor immune escape from natural killer cells and predicts the prognosis in small cell lung cancer

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Oncology Research 2025年第1期33卷 213-224页

作者： SHIQIN jiang YICHUN TANG FENG ma YUCHUN NIU LEI SUN Department of Clinical Pharmacy Shenzhen Hospital of Integrated Traditional Chinese and Western MedicineShenzhen518104China Department of Pathology Zhujiang HospitalSouthern Medical UniversityGuangzhou510280China Department of Radiation Oncology The First People’s Hospital of FoshanFoshan528000China Department of Oncology The First Affiliated Hospital of Jinan UniversityJinan UniversityGuangzhou510630China Department of Oncology The First Dongguan Affiliated HospitalGuangdong Medical UniversityDongguan523721China

Objective:Small cell lung cancer(SCLC)is commonly recognized as the most fatal lung cancer *** substantial advances in immune checkpoint blockade therapies for treating solid cancers,their benefits are limited to a minority of patients with *** the present study,novel indicators for predicting the outcomes and molecular targets for SCLC treatment were ***:We conducted bioinformatics analysis to identify the key genes associated with tumor-infiltrating lymphocytes in *** functional role of the key gene identified in SCLC was determined both in vitro and in ***:A significant correlation was observed between patient survival and CD56dim natural killer(NK)cell ***,we noted that the hub gene ubiquitin-specific protease 1(USP1)is closely correlated with both CD56dim NK cells and overall survival in *** analysis revealed that USP1 is upregulated in *** addition,gene set enrichment analysis revealed that USP1 overexpression hinders NK cell-mediated immune *** co-cultivating NK-92 cells with SCLC cells,we demonstrated that NK cell cytotoxicity against SCLC could be improved either via USP1 knock-down or pharmacological ***,using a nude-mice xenograft tumor model,we noted that USP1 inhibition effectively suppressed tumor proliferation and increased the expression of NK cell-associated ***:Our study findings highlight the importance of NK cells in regulating ***1 overexpression can inhibit NK cell-mediated immunity;therefore,USP1 may serve not only as a prognostic biomarker but also as a potential molecular target of SCLC therapy.

关键词： Ubiquitin-specific protease 1(USP1) Natural killer(NK)cell Small cell lung cancer(SCLC) Prognosis Immune escape

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Near-perfect replication on amorphous alloys through active force modulation based on machine learning/neural network parameter prediction

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Science China(Physics,Mechanics & Astronomy) 2025年第1期Mechanics & Astronomy) .卷 181-191页

作者： Senkuan Meng Zheng Wang ruisong Zhu ruijie Liu jiang ma Lina Hu Weihua Wang Key Laboratory for Liquid-Solid Structural Evolution and Processing of materials (Ministry of Education) School of Materials Science and Engineering Shandong University College of Mechatronics and Control Engineering Shenzhen University Songshan Lake materials Laboratory Institute of Physics Chinese Academy of Sciences

As a microforming technique, micro/nano-structural replication possesses advantages of high precision and efficiency. With the remarkable superplasticity in the supercooled liquid region, amorphous alloys or metallic glasses(MGs) are regarded as ideal materials for miniature fabrication. However, due to the intrinsic metastable nature of supercooled liquids, the design of imprinting processes for MGs poses a challenge. In the past, process parameters have largely relied on trial-and-error *** this work, a low-frequency active force modulation system is employed to apply a stable, precise, and real-time feedback stress field for imprinting of MG samples. Low-frequency vibrations can facilitate the filling of microstructures on the template surface by reducing the effective viscosity of the supercooled liquid. With the dataset composed of orthogonal experiments, a machine learning strategy based on back-propagation(BP) neural networks was utilized to construct a 3D parameter space for temperature, stress, and time, and to predict the corresponding filling ratio. Furthermore, the optimal combination of imprinting process parameters was identified, and its filling ratio was experimentally validated to reach as high as 0.94. The near-perfect replication of microstructures confirms the superiority of the active force modulation system and the data-driven strategy of machine learning-assisted parameter design. At the same time, this one-step microforming process provides a new approach to addressing the accuracy-cost trade-off dilemma in precision manufacturing.

关键词： metallic glass amorphous alloy microforming imprinting machine learning

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应用稳定性行星轮式越障机构优化设计

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机械设计与制造 2017年第7期 131-135页

作者：黄艳潘江如马良新疆工程学院新疆乌鲁木齐830023

行星轮式越障行走机构可应用于矿产开采运输。针对具有4组行星轮系组成的越障机构,机构轮系可根据不同地形状况在定轴和行星轮系之间转换。基于机构的行驶可靠性,采用模糊优化相关理论对行星轮系进行优化,确定机构的最优结构尺寸;建立... 详细信息

行星轮式越障行走机构可应用于矿产开采运输。针对具有4组行星轮系组成的越障机构,机构轮系可根据不同地形状况在定轴和行星轮系之间转换。基于机构的行驶可靠性,采用模糊优化相关理论对行星轮系进行优化,确定机构的最优结构尺寸;建立机构在工作过程中的力学模型和稳定性力学模型。基于ADmaS建立了行星轮式越障机构虚拟样机和典型的地面谱(单边越0.45m障碍、0.45m壕沟、横坡道转向),对优化后不同工况下机构的稳定性进行分析。结果可知:行星轮式越障机构通过驱动轮系在定轴轮系和行星轮系间的转换,实现其越障、跨沟、爬坡等不同工况运行;不同运行工况下,机构的稳定性良好;分析结果为此类结构参数及控制参数确定提供理论基础。

关键词：行星轮式越障机构模型地面谱稳定性定轴轮系

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苯硼酸功能化聚合物纳米载体用于蛋白质药物胞内递送

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高分子学报 2023年第4期54卷 451-466页

作者：陈华崔力允李圆凤刘勇马如江史林启南开大学化学学院高分子化学研究所天津300071 温州医科大学附属第一医院转化医学实验室温州325000 国科温州研究院(温州生物材料与工程研究所) 温州325001

蛋白质药物在疾病治疗方面具有广泛应用,但它们的低细胞膜穿透性往往导致生物利用度较低.近年来,人们开发了一系列纳米载体用于提高蛋白质药物的胞内递送效率,其中基于苯硼酸及其衍生物的聚合物纳米载体显示出良好的应用前景.本文综述... 详细信息

蛋白质药物在疾病治疗方面具有广泛应用,但它们的低细胞膜穿透性往往导致生物利用度较低.近年来,人们开发了一系列纳米载体用于提高蛋白质药物的胞内递送效率,其中基于苯硼酸及其衍生物的聚合物纳米载体显示出良好的应用前景.本文综述了苯硼酸功能化聚合物纳米载体在蛋白质药物胞内递送方面的最新研究进展.首先,简要介绍了苯硼酸的化学性质及其二醇、pH和活性氧(ROS)响应性.其次,从苯硼酸与蛋白质药物的结合方式不同出发,重点综述了通过动态共价作用和N→B配位等非共价作用构筑的苯硼酸功能化聚合物纳米载体在蛋白质药物胞内递送方面的典型研究实例,并对这些载体的组成、构筑方式和响应性释放机制进行了分析、总结.最后,介绍了利用苯硼酸增强细胞摄取和促进药物透过血脑屏障方面的研究进展.希望能为设计制备基于苯硼酸的新型蛋白质药物胞内递送体系提供借鉴.

关键词：蛋白质药物胞内递送苯硼酸响应性释放纳米载体

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