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Molecular Mechanisms of Intracellular Delivery of Nanoparticles Monitored by an Enzyme‑Induced Proximity Labeling

Nano-Micro Letters 2024年第6期16卷 14-37页

作者： Junji Ren Zibin Zhang Shuo Geng Yuxi Cheng huize han Zhipu Fan Wenbing Dai Hua Zhang Xueqing Wang Qiang Zhang Bing He Department of Pharmaceutics School of Pharmaceutical Sciences Peking University38 Xueyuan RdHaidian DistrictBeijing 100191People’s Republic of China

Achieving increasingly finely targeted drug delivery to organs,tissues,cells,and even to intracellular biomacromolecules is one of the core goals of *** the delivery destination is refined to cellular and subcellular targets,it is essential to explore the delivery of nanomedicines at the molecular ***,due to the lack of technical methods,the molecular mechanism of the intracellular delivery of nanomedicines remains unclear to ***,we develop an enzyme-induced proximity labeling technology in nanoparticles(nano-EPL)for the real-time monitoring of proteins that interact with intracellular ***(lactic-co-glycolic acid)nanoparticles coupled with horseradish peroxidase(HRP)were fabricated as a model(HRP(+)-PNPs)to evaluate the molecular mechanism of nano delivery in *** adding the labeling probe biotin-phenol and the catalytic substrate H_(2)O_(2)at different time points in cellular delivery,nano-EPL technology was validated for the real-time in situ labeling of proteins interacting with ***-EPL achieves the dynamic molecular profiling of 740 proteins to map the intracellular delivery of HRP(+)-PNPs in macrophages over *** on dynamic clustering analysis of these proteins,we further discovered that different organelles,including endosomes,lysosomes,the endoplasmic reticulum,and the Golgi apparatus,are involved in delivery with distinct participation *** importantly,the engagement of these organelles differentially affects the drug delivery efficiency,reflecting the spatial–temporal heterogeneity of nano delivery in *** summary,these findings highlight a significant methodological advance toward understanding the molecular mechanisms involved in the intracellular delivery of nanomedicines.

关键词： Enzyme-induced proximity labeling Intracellular delivery Nano-protein interaction Dynamic molecule profiling Macrophages

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Lipid-based nanoparticles for cancer immunotherapy

Medical Review

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Medical Review 2023年第3期3卷 230-269页

作者： Shumin Fan huize han Zhicheng Yan Yao Lu Bing He Qiang Zhang Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems State Key Laboratory of Natural and Biomimetic DrugsSchool of Pharmaceutical SciencesPeking UniversityBeijingChina Ningbo Institute of Marine Medicine Peking UniversityNingbo 315832Zhejiang ProvinceChina

As the fourth most important cancer management strategy except surgery, chemotherapy and radiotherapy, cancer immunotherapy has been confirmed to elicitdurable antitumor effects in the clinic by leveraging thepatient’s own immune system to eradicate the cancer ***, the limited population of patients who benefitfrom the current immunotherapies and the immune relatedadverse events hinder its development. The immunosuppressive microenvironment is the main cause of the failure,which leads to cancer immune evasion and immunity cycleblockade. Encouragingly, nanotechnology has been engineered to enhance the efficacy and reduce off-target toxicityof their therapeutic cargos by spatiotemporally controllingthe biodistribution and release kinetics. Among them, lipid-based nanoparticles are the first nanomedicines to makeclinical translation, which are now established platforms fordiverse areas. In this perspective, we discuss the availablelipid-based nanoparticles in research and market here, thendescribe their application in cancer immunotherapy, withspecial emphasis on the T cells-activated and macrophagestargeted delivery system. Through perpetuating each step ofcancer immunity cycle, lipid-based nanoparticles can reduceimmunosuppression and promote drug delivery to triggerrobust antitumor response.

关键词： cancer immunity cycle cancer immunotherapy lipid-based nanoparticles macrophages T cells

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免疫功能低下患者肺孢子菌肺炎的临床特点

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中华传染病杂志 2020年第7期38卷 422-425页

作者：孙禾吴晓东韩蕙泽施毅李强同济大学附属东方医院呼吸与危重症医学科上海200120 南京大学医学院附属金陵医院呼吸与危重症医学科 210002

目的了解免疫功能低下患者肺孢子菌肺炎(Pneumocystis carinii pneumonia,PCP)的临床特征。方法回顾性分析2018年3月至2019年3月上海同济大学附属东方医院收治的15例PCP患者的临床资料,观察其临床表现、实验室检查指标、影像学特征、合... 详细信息

目的了解免疫功能低下患者肺孢子菌肺炎(Pneumocystis carinii pneumonia,PCP)的临床特征。方法回顾性分析2018年3月至2019年3月上海同济大学附属东方医院收治的15例PCP患者的临床资料,观察其临床表现、实验室检查指标、影像学特征、合并症、治疗和转归等。结果15例PCP患者中,恶性血液病11例,接受骨髓造血干细胞移植4例。移植患者PCP发病时间为移植后(5.82±2.33)个月。15例患者胸部计算机断层成像检查均表现为两肺以肺门为中心的弥漫性磨玻璃样渗出影,外周血CD4^+T淋巴细胞计数均明显下降,为(135.17±74.83)/μL;乳酸脱氢酶(lactic acid dehydrogenase,LDH)明显升高,为(576.18±228.01)U/L;氧合指数明显减低,为(188.47±41.03)mmHg(1 mmHg=0.133 kPa);血清和支气管肺泡灌洗液(bronchoalveolar lavage fluid,BALF)中1,3-β-D-葡聚糖均升高,分别为(1862.81±157.73)ng/L和(1216.97±957.16)ng/L。BALF宏基因组二代病原体测序结果示,耶氏肺孢子菌序列数为120~14383个。合并巨细胞病毒(cytomegalovirus,CMV)感染9例,EB病毒感染4例,革兰阴性菌感染2例。经复方磺胺甲唑和卡泊芬净治疗后,好转13例,死亡2例。结论恶性血液病和接受骨髓造血干细胞移植者均是PCP的高危人群,PCP患者血清CD4^+T淋巴细胞计数下降,LDH和1,3-β-D-葡聚糖水平升高,宏基因组二代病原体测序对早期诊断有重要意义。

关键词：肺孢子菌肺炎血液肿瘤骨髓造血干细胞移植

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头孢他啶-阿维巴坦治疗碳青霉烯耐药的肺炎克雷伯菌脓毒性休克的临床分析

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中华重症医学电子杂志 2021年第1期7卷 76-80页

作者：孙禾何春凤吴晓东韩蕙泽施毅李强同济大学附属东方医院呼吸与危重症医学科上海200120 南京大学医学院附属金陵医院呼吸与危重症医学科南京210002

目的探讨头孢他啶-阿维巴坦(CZA)治疗耐碳青霉烯耐药的肺炎克雷伯菌(CRKP)脓毒性休克的效果和安全性。方法回顾性分析2019年8月至2020年5月在上海市同济大学附属东方医院RICU收住的4例经CZA治疗的CRKP感染致脓毒性休克患者的临床资料。... 详细信息

目的探讨头孢他啶-阿维巴坦(CZA)治疗耐碳青霉烯耐药的肺炎克雷伯菌(CRKP)脓毒性休克的效果和安全性。方法回顾性分析2019年8月至2020年5月在上海市同济大学附属东方医院RICU收住的4例经CZA治疗的CRKP感染致脓毒性休克患者的临床资料。收集患者的临床特征、生化指标、细菌培养及药敏试验结果、抗菌药物种类、CZA治疗前后的序贯器官衰竭估计评分(SOFA)评分,评估患者临床疗效、用药不良反应等。结果4例患者中女性2例,男性2例,年龄72~79岁。分别在肺泡灌洗液、胆汁引流液或血液标本中检出肺炎克雷伯菌,培阳标本的药敏试验均提示碳青霉烯类抗生素耐药,对CZA敏感。经CZA治疗后患者SOFA评分、临床表现、炎症指标等均明显好转。4例患者均好转出院,未发现抗感染药物治疗相关的不良反应。结论CZA对耐碳青霉烯肺炎克雷伯菌感染导致的脓毒性休克具有良好的疗效和安全性。

关键词：耐碳青霉烯肺炎克雷伯菌脓毒性休克头孢他啶-阿维巴坦

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基于五脏相关理论分期辨治慢性心衰

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吉林中医药 2024年第2期44卷 149-153页

作者：辛宇咛刘爱东刘迎辉成光宇李双娣吕珊韩蕙泽长春中医药大学长春130117 长春中医药大学附属第三临床医院长春130117 长春中医药大学附属医院长春130021

慢性心衰是各种心脏疾病发展至终末阶段的复杂综合征,其发生发展是各脏腑共同作用的结果。国医大师任继学教授、邓铁涛教授均倡导从五脏相关出发辨治慢性心衰,刘爱东教授总结多年临证经验,深入体会五脏相关理论与慢性心衰的科学内涵,探... 详细信息

慢性心衰是各种心脏疾病发展至终末阶段的复杂综合征,其发生发展是各脏腑共同作用的结果。国医大师任继学教授、邓铁涛教授均倡导从五脏相关出发辨治慢性心衰,刘爱东教授总结多年临证经验,深入体会五脏相关理论与慢性心衰的科学内涵,探讨在该理论指导下分期辨治慢性心衰。根据病程不同阶段,主要分为三期,Ⅰ期多以心气不足,肺气壅塞为主,Ⅱ期多见脾虚肺闭,心肝血瘀,而病至Ⅲ期多为五脏衰弱,虚实夹杂,并附医案一则详细阐释临证思路,以飨同道。

关键词：五脏相关慢性心衰分期辨治

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The Plant Cytoskeleton and Crosslinking Factors

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CellBio 2020年第2期9卷 85-99页

作者： Fangfang He huize Chen Rong han College of Life Science Shanxi Normal University Linfen China Higher Education Key Laboratory of Plant Molecular and Environmental Stress Response (Shanxi Normal University) in Shanxi Province Linfen China

Cytoskeleton exists in all eukaryotes and is involved in many significant cytobiological processes, especially the movements and developmental changes of plant cells. The cytoskeleton consists of microtubule (MT), microfilament (MF), and intermediate filament (IF). MT and MF are vital components of plant cytoskeleton. Crosslinking factor acts as a bridge between MF and MT. They play an important role in cellular life process and have always been a hot topic and key point in plant cytobiology, and the IF is a difficult point in this field. In this paper, the latest research on the cytoskeleton of plants is introduced, which focuses on the structure and dynamics of MT, MF, and IF, and summarizes the crosslinking factors between MT and MF. Also, the paper prospects the future research direction of plant cytoskeleton and the possible research hotspot, which provides a certain reference for people to continue to explore the function of plant cytoskeleton in the future.

关键词： Plant Cytoskeleton Crosslinking Factor

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Different Doses of the Enhanced UV-B Radiation Effects on Wheat Somatic Cell Division

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CellBio 2015年第2期4卷 30-36页

作者： Feifeng Liu huize Chen Rong han College of Life Science Shanxi Normal University Linfen China Higher Education Key Laboratory of Plant Molecular and Environmental Stress Response (Shanxi Normal University) in Shanxi Province Linfen China

Being sessile, plants are continuously exposed to DNA-damaging agents presenting in the environment such as ultraviolet (UV). Sunlight acts as an energy source for photosynthetic plants;hence, avoidance of UV radiations (namely, UV-A, 315 - 400 nm;UV-B, 280 - 315 nm;and UV-C, 1 group: 4.05 kJ•m-2•d-1, B2 group: 10.08 kJ•m-2•d-1, B3 group: 7.05 kJ•m-2•d-1, B4 group: 23.02 kJ•m-2•d-1) treatment wheat, then, explored on the growth of wheat root and wheat root tip cell of chromosome aberration effect. In wheat, root-tip cells were observed with confocal laser scanning microscopy (CLSM), the results showed that low doses of B1 group (4.05 kJ•m-2•d-1) promoted the growth of wheat root and cell mitosis frequency. But high dose of B2 group (10.08 kJ•m-2•d-1), B3 group (17.05 kJ•m-2•d-1), B4 group (23.02 kJ•m-2•d-1) inhibited the growth of wheat root tip, and made crooked growth of wheat root, and inhibited the wheat root tip cell mitotic frequency and processed that induce root tip cells of wheat produce all kinds of aberration of chromosome in the interphase containing “multiple nucleoli nuclei”, “incomplete nuclei”, “long round nuclei”, “bean sprouts nucleus”. In mitosis M period contains “dissociative chromosome”, “chromosome bridge”, “adhesion chromosome”, “multi-bundle divide”, “nuclear anomalies”. After, high doses of enhanced UV-B radiation treatment, most of the cell cycle anomaly concentrated in mitosis interphase. In mitosis M period, with UV-B radiation dose enhanced chromosome aberration rate was on the rise and the aberration types also increasing.

关键词： Wheat Enhanced UV-B Radiation Chromosome Aberration Confocal Laser Scanning Microscopy (CLSM)

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Advances in the Application of Virus-Induced Gene Silencing in Plants

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American Journal of Plant Sciences 2019年第9期10卷 1649-1661页

作者： Ying Zhang huize Chen Rong han Higher Education Key Laboratory of Plant Molecular and Environment Stress Response Shanxi Normal University Linfen China School of Life Science Shanxi Normal University Linfen China

VIGS (Virus-induced gene silencing) can effectively silence target genes at the RNA level to investigate their functions. The virus vectors used for silencing are divided into three categories, DNA virus, RNA virus, and satellite virus, which can be used to silence the target genes in different species based on existing research. The genes used as markers for silencing system identification include PDS and PCNA. VIGS can be applied to some plants, in particular cash crops and fruit trees, to study their disease-resistance genes and genes related to growth and development to provide a basis for improving crop characteristics.

关键词： VIGS Application VIGS Vector Marker Genes

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The Effects of He-Ne Laser and Enhanced Ultraviolet-B Radiation on Proliferating-Cell Nuclear Antigen in Wheat Seedlings

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American Journal of Plant Sciences 2015年第8期6卷 1206-1214页

The level of ultraviolet-B (UV-B) radiation on the Earth’s surface has increased due to depletion of the ozone layer. Here, we explored the effects of continuous wave He-Ne laser irradiation (632 nm, 5 mW·mm-2, 2 min·d-1) on proliferating-cell nuclear antigen (PCNA) damage repair function of wheat seedlings exposed to enhanced UV-B radiation (10.08 kJ·m-2·d-1) at the early growth stages. Wheat seedlings were irradiated with enhanced UV-B, He-Ne laser treatment or a combination of the two. We explored the transcripts of PCNA in each treatment group using RT-PCR. In addition, total proteins were extracted from the 7-day-old wheat leaves, analyzed by SDS-PAGE and identified by western blot. The results showed that the transcription of PCNA was weakened following UV-B radiation compared to the control. However, when seedlings were subjected to elevated UV-B-damaging radiation followed by He-Ne laser irradiation, the expression of PCNA was signifi-cantly higher than UV-B radiation alone. These results suggest that He-Ne laser has an active role in repairing the UV-B damaging effects. In order to further investigate the function of PCNA, dynamic arrangements of PCNA in wheat root-tip cells were observed with confocal laser scanning microscopy (CLSM). The PCNA was marked fluorescent dimming and strength weakened in en-hanced UV-B radiation (UV-B) compared with the control group (CK) during processing. It shows that PCNA may be involved in the separation of chromosomes.

关键词： Wheat PCNA UVB Radiation He-Ne Laser CLSM

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Reinforced interface endows the lithium anode with stable cycle at high-temperature of 80℃

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Journal of Energy Chemistry 2023年第3期78卷 325-332,I0010页

作者： Yuhao Zhu Xieyu Xu Qingpeng Guo Yu han Haolong Jiang huize Jiang Hui Wang Pavel V.Evdokimov Olesya O.Kapitanova Valentyn S.Volkov Yongjing Wang Shizhao Xiong Chunman Zheng Kai Xie Xingxing Jiao Yangyang Liu College of Aerospace Science and Engineering National University of Defense TechnologyChangsha 410073HunanChina Department of Materials Science Lomonosov Moscow State UniversityMoscow 119991Russia Center for Photonics and 2D Materials Moscow Institute of Physics and TechnologyDolgoprudnyMoscow 141701Russia State Key Laboratory for Mechanical Behavior of Materials Xi’an Jiaotong UniversityXi’an 710049ShaanxiChina Autonomous Noncommercial Organization"ID&AS:Inter-Disciplinary&Advanced Studies Center" Moscow 127495Russia

Embracing ultrahigh theoretical capacity of 3860 mA h g^(-1)and the lowest reduction potential of-3.04 V(versus standard hydrogen electrode),lithium(Li) is considered as the "holy grail" material for pursuing higher energy density,of which application has been challenged due to the unstable interface caused by the non-uniform electrodeposition as well as high chemical *** at higher temperature can be recommended to uniform electrodeposition of Li ***,the intrinsic side-reaction between Li metal anode and electrolyte is inevitably aggravated and thus fosters the failure of Li metal anode rapidly with uneven ***,a kind of temperature-tolerated ionic liquid(1-methyl-3-ethylimidazole bis(fluorosulfo nyl)imide/lithium bis(trifluoromethylsulfo nyl)imide,EF/LT)based electrolyte that matrixed with poly(vinylidene fluoride-hexafluoropropylene) was designed to maintain the interfacial stabilization of Li metal due to the weak interfacial reaction and uniform electrodeposition at high temperature of 80℃.It is the matter that the 660-h cycle with lower polarization is achieved with EF/LT-based electrolyte at temperature of 80 ℃ and the full cell embraces outstanding cyclic performance,without capacity fading within 100 ***,a door for practical application of Li metal anode for higher energy density as the carbon neutrality progresses in the blooming human society has been opened gradually.

关键词： Lithium metal anode Uniform electrodeposition High-temperature operation Temperature-tolerated electrolyte Ionic liquid

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