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exosome regulation of immune response mechanism:Pros and cons in immunotherapy

Bioactive Materials 2024年第2期32卷 124-146页

作者： Julien Milon Essola Mengjie Zhang Haiyin Yang Fangzhou Li Bozhang Xia Jacques François Mavoungou Abid Hussain Yuanyu Huang School of Life Science Advanced Research Institute of Multidisciplinary ScienceSchool of Medical TechnologyKey Laboratory of Molecular Medicine and BiotherapyKey Laboratory of Medical Molecule Science and Pharmaceutics EngineeringBeijing Institute of TechnologyBeijing100081China CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety CAS Center for Excellence in NanoscienceNational Center for Nanoscience and Technology of ChinaNo.11First North RoadZhongguancunBeijing100190PR China University of Chinese Academy of Sciences.Beijing 100049 PR China Rigerna Therapeutics Co.Ltd. China Universit´e Internationale de Libreville Libreville20411Gabon Central and West African Virus Epidemiology Libreville2263Gabon D´epartement de phytotechnologies Institut National Sup´erieur d’Agronomie et de BiotechnologieUniversit´e des Sciences et Techniques de MasukuFranceville901Gabon Institut de Recherches Agronomiques et Forestiers Centre National de la Recherche Scientifique et du d´eveloppement TechnologiqueLibreville16182Gabon

Due to its multiple features,including the ability to orchestrate remote communication between different tissues,the exosomes are the extracellular vesicles arousing the highest interest in the scientific *** size,established as an average of 30-150 nm,allows them to be easily uptaken by most *** to the type of cells-derived exosomes,they may carry specific biomolecular cargoes used to reprogram the cells they are interacting *** certain circumstances,exosomes stimulate the immune response by facilitating or amplifying the release of foreign antigens-killing cells,inflammatory factors,or antibodies(immune activation).Meanwhile,in other cases,they are efficiently used by malignant elements such as cancer cells to mislead the immune recognition mechanism,carrying and transferring their cancerous cargoes to distant healthy cells,thus contributing to antigenic invasion(immune suppression).exosome dichotomic patterns upon immune system regulation present broad advantages in *** perfect comprehension,from its early biogenesis to its specific interaction with recipient cells,will promote a significant enhancement of immunotherapy employing molecular biology,nanomedicine,and nanotechnology.

关键词： exosome Immune activation Immune suppression Tumor cells RNAs

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exosome is involved in liver graft protection after remote ischemia reperfusion conditioning

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Hepatobiliary & Pancreatic Diseases International 2023年第5期22卷 498-503页

作者： Jian-Hui Li Jun-Jun Jia Ning He Xue-Lian Zhou Yin-Biao Qiao Hai-Yang Xie Lin Zhou Shu-Sen Zheng Department of Hepatobiliary and Pancreatic Surgery Department of Liver TransplantationShulan(Hangzhou)HospitalZhejiang Shuren University School of MedicineHangzhou 310022China NHC Key Laboratory of Combined Multi-organ Transplantation Hangzhou 310022China Division of Hepatobiliary Pancreatic Surgery First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China Department of Endocrinology Children’s HospitalZhejiang University School of MedicineHangzhou 310052China

Background:Remote ischemic perconditioning(RIPerC)has been demonstrated to protect grafts from hepatic ischemia-reperfusion injury(IRI).This study investigated the role of exosomes in RIPerC of liver grafts in ***:Twenty-five rats(including 10 donors)were randomly divided into five groups(n=5 each group):five rats were used as sham-operated controls(Sham),ten rats were for orthotopic liver transplantation(OLT,5 donors and 5 recipients)and ten rats were for OLT+RIPerC(5 donors and 5 recipients).Liver architecture and function were ***:Compared to the OLT group,the OLT+RIPerC group exhibited significantly improved liver graft histopathology and liver function(Pexosomes and the level of P-Akt were increased in the OLT+RIPerC ***:RIPerC effectively improves graft architecture and function,and this protective effect may be related to the increased number of *** upregulation of P-Akt may be involved in underlying mechanisms.

关键词： exosome P-Akt Ischemia-reperfusion injury Remote ischemic perconditioning

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exosome-guided direct reprogramming of tumor-associated macrophages from protumorigenic to antitumorigenic to fight cancer

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Bioactive Materials 2023年第7期25卷 527-540页

作者： Hyosuk Kim Hyun-Ju Park Hyo Won Chang Ji Hyun Back Su Jin Lee Yae Eun Park Eun Hye Kim Yeonsun Hong Gijung Kwak Ick Chan Kwon Ji Eun Lee Yoon Se Lee Sang Yoon Kim Yoosoo Yang Sun Hwa Kim Medicinal Materials Research Center Biomedical Research InstituteKorea Institute of Science and TechnologySeoul02792Republic of Korea Department of Functional Genomics KRIBB School of BioscienceKorea University of Science and Technology(UST)Daejeon34141Republic of Korea Department of Otolaryngology Asan Medical CenterUniversity of Ulsan College of MedicineSeoul05505Republic of Korea Chemical&Biological Integrative Research Center Biomedical Research InstituteKorea Institute of Science and TechnologySeoul02792Republic of Korea Department of Biotechnology College of Life Sciences and BiotechnologyKorea UniversitySeoul02841Republic of Korea Department of Life Sciences Korea UniversitySeoul02841Republic of Korea

Highly immunosuppressive tumor microenvironment containing various protumoral immune cells accelerates malignant transformation and treatment *** particular,tumor-associated macrophages(TAMs),as the predominant infiltrated immune cells in a tumor,play a pivotal role in regulating the immunosuppressive tumor *** a potential therapeutic strategy to counteract TAMs,here we explore an exosome-guided in situ direct reprogramming of tumor-supportive M2-polarized TAMs into tumor-attacking M1-type *** derived from M1-type macrophages(M1-Exo)promote a phenotypic switch from anti-inflammatory M2-like TAMs toward pro-inflammatory M1-type macrophages with high conversion *** M1 macrophages possessing protein-expression profiles similar to those of classically activated M1 macrophages display significantly increased phagocytic function and robust cross-presentation ability,potentiating antitumor immunity surrounding the ***,these M1-Exo also lead to the conversion of human patient-derived TAMs into M1-like macrophages that highly express MHC class II,offering the clinical potential of autologous and allogeneic exosome-guided direct TAM reprogramming for arming macrophages to join the fight against cancer.

关键词： exosome Cancer therapy Tumor microenvironment Tumor-associated macrophage Direct conversion

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exosome-mediated cellular crosstalk within the tumor microenvironment upon irradiation

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Cancer Biology & Medicine 2021年第1期18卷 21-33页

作者： Chuanshi He Ling Li Linlin Wang Wanrong Meng Yaying Hao Guiquan Zhu Department of Stomatology Sichuan Cancer HospitalSichuan Key Laboratory of Radiation OncologySchool of MedicineUniversity of Electronic Science and Technology of China State Key Laboratory of Oral Diseases National Clinical Research Centre for Oral DiseasesDepartment of Head and Neck OncologyWest China Hospital of StomatologySichuan UniversityChengdu 610041China

Radiotherapy is one of the most effective treatment methods for various solid *** signal transduction between cancer cells and stromal cells within the irradiated microenvironment is important in cancer development and treatment ***,initially considered as"garbage bins"for unwanted from cells,are now understood to perform a variety of functions in interactions within the tumor ***-mediated regulation processes are rebuilt under the irradiation stimuli,because the exosome production,uptake,and contents are markedly modified by *** turn,irradiation-modified exosomes may modulate the cell response to irradiation through feedback ***,we review current knowledge and discuss the roles of exosome-mediated interactions between cells under radiotherapy conditions.

关键词： Radiotherapy tumor microenvironment exosome irradiation extracellular vesicle

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exosome-Coated Zeolitic Imidazolate Framework Nanoparticles for Intracellular Detection of ATP

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Chinese Journal of Chemistry 2021年第8期39卷 2107-2112页

作者： Wenxing Lv Ziwei Han Yike Li Yanjuan Huang Jiashu Sun Xiaoquan Lu Chao Liu Tianjin Key Laboratory of Molecular Optoelectronic Sciences Department of ChemistrySchool of ScienceTianjin UniversityTianjin 300072China Beijing Engineering Research Center for BioNanotechnology CAS Key Laboratory of Standardization and Measurement for NanotechnologyCAS Center for Excellence in NanoscienceNational Center for Nanoscience and TechnologyBeijing 100190China School of Future Technology University of Chinese Academy of SciencesBeijing 100049China Key Laboratory of Bioelectrochemistry and Environmental Analysis of Gansu Province College of Chemistry and Chemical EngineeringNorthwest Normal UniversityLanzhouGansu 730070China

The intracellular delivery of metal-organic frameworks(MOFs)encapsulated with functional biomolecules represents a promising av-enue in the field of biomedicine and *** improve the cellular uptake efficiency of MOFs,here we report the fabrication of cancer cell-derived exosome membra ne(EM)-coated zeolitic imidazolate framework-8(EM-ZIF-8)nan oparticles by using a microfluidic son ication device.

关键词： ATP exosome Metal-organic frameworks Microreactors Nan oparticles

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exosome-Transmitted miR-224-5p Promotes Colorectal Cancer Cell Proliferation via Targeting ULK2 in p53-Dependent Manner

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Biomedical and Environmental Sciences 2024年第1期37卷 71-84页

作者： YANG Le Mei ZHENG Qi LIU Xiao Jia LI Xian Xian Veronica Lim CHEN Qi ZHAO Zhong Hua WANG Shu Yang Department of Pathology School of Basic MedicineFudan UniversityShanghai 200032China Department of Pathology Dunedin School of MedicineUniversity of OtagoDunedin 9054New Zealand Department of Pathology Huashan HospitalFudan UniversityShanghai 200040China Shanghai Cancer Institute Renji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200127China Teladoc Health Inc Shanghai 200335China Shanghai Medical College Fudan UniversityShanghai 200032China Shanghai Key Laboratory of Medical Imaging Computing and Computer Assisted Intervention Shanghai 200032China

Objective To investigate the role and molecular mechanism of exosomal miR-224-5p in colorectal cancer(CRC).Methods The miR-224-5p expression in CRC patient tissues and cell-derived exosomes was measured by laser capture microdissection and qRT-PCR,***-luciferase reporter gene assay was used to determine the target gene of *** protein expressions of p53 and unc-51 like kinase 2(ULK2)in CRC cells were detected by western *** cytometry was used to detect cell cycle and *** proliferation was measured by CCK8 and EdU *** The miR-224-5p expression was upregulated in CRC tissues and increased progressively with the rise of CRC *** cells secreted extracellular miR-224-5p mainly in an exosome-dependent manner,and then miR-224-5p could be transferred to surrounding tumor cells to regulate cell proliferation in the form of autocrine or ***,ULK2 was characterized as a direct target of miR-224-5p and was downregulated in CRC ***,ULK2 inhibited CRC cell proliferation in a p53-dependent ***,exosome-derived miR-224-5p partially reversed the proliferation regulation of ULK2 on CRC *** Our findings demonstrate that exosome-transmitted miR-224-5p promotes p53-dependent cell proliferation by targeting ULK2 in CRC,which may offer promising targets for CRC prevention and therapy.

关键词： miR-224-5p exosome ULK2 p53 Cell proliferation Colorectal cancer

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exosome-based drug delivery systems in cancer therapy

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Chinese Chemical Letters 2023年第2期34卷 89-96页

作者： Tianqi Wang Yanan Fu Shengjie Sun Chenyi Huang Yunfei Yi Junqing Wang Yang Deng Meiying Wu School of Pharmaceutical Sciences(Shenzhen) Shenzhen Campus of Sun Yat-sen UniversityShenzhen 518107China

exosome, which is a kind of extracellular vesicles with size around 40-160 nm, plays an important role in cell-to-cell communication in multiple diseases. Especially in tumor microenvironment, exosomes are the important pathway to transit proteins, nucleic acids and small molecules between different kinds of cells. Based on these characteristics, exosomes are served as both therapeutic agents and drug delivery systems in cancer therapy. In this review, the applications of exosomes as drug delivery systems in cancer therapy were summarized and classified according to the cell source of the exosomes, including normal cells, immune cells and tumor cells. Different modifications of exosomes and drug loading methods were presented. Finally, some challenges that hindered the clinical translation of exosomes were also discussed.

关键词： exosome Drug delivery Cancer therapy Immunotherapy Macrophages Tumor cells

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exosome treatment for stroke with diabetic comorbidity

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Neural Regeneration Research 2022年第2期17卷 315-317页

作者： Poornima Venkat Michael Chopp Department of Neurology Henry Ford HospitalDetroitMIUSA Department of Physics Oakland UniversityRochesterMIUSA

Ischemic stroke is a cerebrovasculardisease with a high risk of mortality andlong-lasting neurological *** advances have resulted in adeclining trend in stroke incidence anddeaths in the United States. However,increas... 详细信息

关键词： mortality morbidity exosome

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Rapid Isolation and Multiplexed Detection of exosome Tumor Markers Via Queued Beads Combined with Quantum Dots in a Microarray

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Nano-Micro Letters 2019年第4期11卷 73-83页

作者： Yanan Bai Yunxing Lu Kun Wang Zule Cheng Youlan Qu Shihui Qiu Lin Zhou Zhenhua Wu Huiying Liu Jianlong Zhao Hongju Mao State Key Laboratory of Transducer Technology Shanghai Institute of Microsystem and Information TechnologyChinese Academy of SciencesShanghai 200050People’s Republic of China Center of Materials Science and Optoelectronics Engineering University of Chinese Academy of SciencesBeijing 100049People’s Republic of China School of Stomatology Dalian Medical UniversityDalian 116044People’s Republic of China

Tumor-derived exosomes are actively involved in cancer progression and metastasis and have emerged as a promising marker for cancer diagnosis in liquid *** of their nanoscale size,complex biogenesis,and methodological limitations related to exosome isolation and detection,advancements in their analysis remain *** technology offers a better analytic approach compared with conventional ***,we developed a bead-based microarray for exosome isolation and multiplexed tumor marker *** this method,exosomes are isolated by binding to antibodies on the bead surface,and tumor markers on the exosomes are detected through quantum dot(QD)*** beads are then uniformly trapped and queued among micropillars in the *** design benefits fluorescence observation by dispersing the signals into every single bead,thereby avoiding optical interference and enabling more accurate test *** analyzed exosomes in the cell culture supernatant of lung cancer and endothelial cell lines,and different lung cancer markers labeled with three QD probes were used to conduct multiplexed detection of exosome surface protein *** cancer-derived samples showed much higher(~sixfold-tenfold)fluorescence intensity than endothelial cell samples,and different types of lung cancer samples showed distinctive marker expression ***,using the chip to detect clinical plasma samples from cancer patients showed good diagnostic power and revealed a well consistency with conventional tests for serological *** results provide insight into a promising method for exosome tumor marker detection and early-stage cancer diagnosis.

关键词： exosome Liquid biopsy Quantum dot Multiplexed detection Cancer diagnosis

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Dynamic nanomechanical characterization of cells in exosome therapy

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Microsystems & Nanoengineering 2024年第4期10卷 185-200页

作者： Ye Chen Zihan Zhang Ziwei Li Wenjie Wu Shihai Lan Tianhao Yan Kainan Mei Zihan Qiao Chen Wang Chuanbiao Bai Ziyan Li Shangquan Wu Jianye Wang Qingchuan Zhang CAS Key Laboratory of Mechanical Behavior and Design of Material Department of Modern MechanicsUniversity of Science and Technology of ChinaHefeiAnhui 230027China Reproductive Medicine Center Department of Obstetrics and GynecologyThe First Affiliated Hospital of Anhui Medical UniversityHefei 230022China Anhui Province Key Laboratory of Reproductive Health and Genetics Anhui Medical UniversityHefei 230022China Department of Cell Biology and Genetics College of Basic Medical SciencesJilin UniversityChangchun 130021China State Key Laboratory of Nonlinear Mechanics Institute of MechanicsChinese Academy of Science15 Beisihuan West RoadBeijing 100190China

exosomes derived from mesenchymal stem cells(MSCs)have been confirmed to enhance cell proliferation and improve tissue *** release their contents into the cytoplasmic solution of the recipient cell to mediate cell expression,which is the main pathway through which exosomes exert therapeutic *** corresponding process of exosome internalization mainly occurs in the early stage of ***,the therapeutic effect of exosomes in the early stage remains to be further *** report that the three-dimensional cell traction force can intuitively reflect the ability of exosomes to enhance the cytoskeleton and cell contractility of recipient cells,serving as an effective method to characterize the therapeutic effect of *** with traditional biochemical methods,we can visualize the early therapeutic effect of exosomes in real time without damage by quantifying the cell traction *** quantitative analysis of traction forces,we found that endometrial stromal cells exhibit short-term cell roundness accompanied by greater traction force during the early stage of exosome *** experiments revealed that exosomes enhance the traction force and cytoskeleton by regulating the Rac1/RhoA signaling pathway,thereby promoting cell *** work provides an effective method for rapidly quantifying the therapeutic effects of exosomes and studying the underlying mechanisms involved.

关键词： exosome traction thereby

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