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A disordered linker in the Polycomb protein Polyhomeotic tunes phase separation and oligomerization

Molecular cell 2025年第11期85卷 2128-2146.e15页

作者： Tim M Gemeinhardt Roshan M Regy Tien M Phan Nanu Pal Jyoti Sharma Olga Senkovich Andrea J Mendiola Heather J Ledterman Amy Henrickson Daniel Lopes Utkarsh Kapoor Ashish Bihani Djamouna Sihou Young C Kim David Jeruzalmi Borries Demeler Chongwoo A Kim Jeetain Mittal Nicole J Francis Montreal Clinical Research Institute (IRCM) Montreal QC Canada Division of Experimental Medicine McGill University Montreal QC Canada. Artie McFerrin Department of Chemical Engineering Texas A&M University College Station TX USA. Department of Biochemistry and Molecular Medicine University of Montreal Montreal QC Canada. Montreal Clinical Research Institute (IRCM) Montreal QC Canada. Department of Biochemistry and Molecular Genetics Midwestern University Glendale AZ USA. Department of Chemistry and Biochemistry The University of Lethbridge Lethbridge AB Canada. Department of Chemistry and Biochemistry City College of New York New York NY USA. Department of Chemical and Biomedical Engineering University of Wyoming Laramie WY USA. Center for Materials Physics and Technology Naval Research Laboratory Washington DC USA. Department of Chemistry and Biochemistry City College of New York New York NY USA Ph.D. Program in Biochemistry The Graduate Center of the City University of New York New York NY USA Ph.D. Program in Biology The Graduate Center of the City University of New York New York NY USA Ph.D. Program in Chemistry The Graduate Center of the City University of New York New York NY USA. Department of Chemistry and Biochemistry The University of Lethbridge Lethbridge AB Canada Department of Chemistry and Biochemistry University of Montana Missoula MT USA. Artie McFerrin Department of Chemical Engineering Texas A&M University College Station TX USA Department of Chemistry Texas A&M University College Station TX USA Interdisciplinary Graduate Program in Genetics and Genomics Texas A&M University College Station TX USA. Electronic address: jeetain@tamu.edu. Division of Experimental Medicine McGill University Montreal QC Canada Department of Biochemistry and Molecular Medicine University of Montreal Montreal QC Canada. Electronic address: nicole.francis@ircm.qc.ca.

Biomolecular condensates are increasingly recognized as key regulators of chromatin organization, yet how their formation and properties arise from protein sequences remains incompletely understood. Cross-species comparisons can reveal both conserved functions and significant evolutionary differences. Here, we integrate in vitro reconstitution, molecular dynamics simulations, and cell-based assays to examine how Drosophila and human variants of Polyhomeotic (Ph)-a subunit of the PRC1 chromatin regulatory complex-drive condensate formation through their sterile alpha motif (SAM) oligomerization domains. We identify divergent interactions between SAM and the disordered linker connecting it to the rest of Ph. These interactions enhance oligomerization and modulate both the formation and properties of reconstituted condensates. Oligomerization influences condensate dynamics but minimally impacts condensate formation. Linker-SAM interactions also affect condensate formation in Drosophila and human cells and growth in Drosophila imaginal discs. Our findings show how evolutionary changes in disordered linkers can fine-tune condensate properties, providing insights into sequence-function relationships.

关键词： CRISPR Drosophila Polycomb analytical ultracentrifugation biochemistry biomolecular condensates gene regulation intrinsically disordered regions molecular dynamics simulations oligomerization phase separation sterile alpha motif

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Corrigendum to "Variations of oxidative potential of PM2.5 in a medium-sized residential city in South Korea measured using three different chemical assays" [920 (2024) 171053]

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The Science of the total environment 2024年 926卷 172075页

作者： Pyung-Rae Kim Sung-Won Park Young-Ji Han Myong-Hwa Lee Thomas M Holsen Cheol-Heon Jeong Greg Evans Agriculture and Life Sciences Research Institute Kangwon National University Chuncheon Gangwon-do 24341 Republic of Korea. Dept. of Interdisciplinary Graduate Program in Environmental and Biomedical Convergence Kangwon National University Chuncheon Gangwon-do 24341 Republic of Korea. Dept. of Environmental Science Kangwon National University Chuncheon Gangwon-do 24341 Republic of Korea Gangwon particle pollution research and management center Kangwon National University Chuncheon Gangwon-do 24341 Republic of Korea. Electronic address: youngji@kangwon.ac.kr. Gangwon particle pollution research and management center Kangwon National University Chuncheon Gangwon-do 24341 Republic of Korea Dept. of Environmental Engineering Kangwon National University Chuncheon Gangwon-do 24341 Republic of Korea. Dept. of Civil and Environmental Engineering Clarkson University Potsdam NY 13699 USA. Dept. of Chemical Engineering and Applied Chemistry University of Toronto Toronto Ontario MS5 3E5 Canada.

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A non-metal single atom nanozyme for cutting off the energy and reducing power of tumors

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Angewandte Chemie 2024年第16期136卷

作者： Junjie Cheng Li Li Duo Jin Yajie Zhang Wenxin Yu Jiaji Yu Jianhua Zou Yi Dai Yang Zhu Manman Liu Miya Zhang Yongfu Sun Yangzhong Liu Xiaoyuan Chen Department of Chemistry Key Laboratory of Precision and Intelligent Chemistry University of Science and Technology of China Hefei 230026 China Hefei National Research Center for Physical Sciences at Microscale University of Science and Technology of China Hefei 230026 China Central Laboratory Department of Biobank Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine Nanjing 210022 China Departments of Diagnostic Radiology Surgery Chemical and Biomolecular Engineering and Biomedical Engineering Yong Loo Lin School of Medicine and College of Design and Engineering National University of Singapore Singapore 119074 Singapore Clinical Imaging Research Centre Centre for Translational Medicine Yong Loo Lin School of Medicine National University of Singapore Singapore 117599 Singapore Nanomedicine Translational Research Program NUS Center for Nanomedicine Yong Loo Lin School of Medicine National University of Singapore Singapore 117597 Singapore Institute of Molecular and Cell Biology Agency for Science Technology and Research (A*STAR) 61 Biopolis Drive Proteos Singapore 138673 Singapore College of Pharmaceutical Sciences Anhui Xinhua University Hefei 230088 China

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Biochemical mechanisms and molecular interactions of vitamins in cancer therapy

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Cancer Pathogenesis and Therapy 2025年第1期3卷 3-15页

作者： Abdullahi T.Aborode Isreal A.Onifade Mercy M.Olorunshola Gladys O.Adenikinju Ibude J.Aruorivwooghene Adeboboye C.Femi Osasere Jude-Kelly Osayawe Abraham Osinuga Ebenezer A.Omojowolo Adekunle F.Adeoye Segun Olapade Ibroadhfrimed O.Acdoelaku Ogundepo D.Moyinoluwa Oluwatosin M.Adeyemo Godfred Y.Scott Ruth A.Ogbonna Emmanuel A.Fajemisin Omama Ehtasham Soyemi Toluwalashe Adetolase A.Bakre Ridwan O.Adesola Seto C.Ogunleye Nnenna R.Anyanwu Terungwa H.lorkula Department of Chemistry Mississippi State UniversityStarkvilleMS 39759USA Department of Biology University at AlbanyAlbanyNY 12222USA Department of Biological Sciences State University of New York at BinghantonBinghamtonNY 13902USA Department of Biological and Environmental Sciences University of Rhode IslandKingstonRI 02881USA Department of Biological Sciences University of Kansas Medical CenterKansasKS 66103USA Department of Microbiology Federal University of TechnologyAkure 340110Nigeria Department of Chemistry and Biochemistry Brigham Young UniversityProvoUT 84602USA 8 Department of Chemical and Biomolecular Engineering University of Nbraska-LincolnLincolnNE 68588USA9 Department of Chemistry University of AlbanyState University of New YorkAlbanyNY 12222USA Department of Mathematics and Statistics Georgia State UniversityAtlantaGA 30302USA Department of Chemistry University of LouisvilleLouisvilleKY 40208USA Department of Biochemistry Federal University of TechnologyAkure 340110Nigeria Deparment of Medical Diagnostics Kwame Nkrumah University of Science and TechnologyKumasi AK385Ghana Department of Research and Development Nasarawa State AIDS and STI Control ProgramNasarawaLafia 96210Nigeria Department of Integrative Biomedical Science University of Cape TownCape'Town 7701South Africa Department of Medicine and Surgery Karachi Medical and Dental CollegeKarachi 74700Pakistan Department of Medicine Lagos State University College of MedicineLagos 10010Nigeria Department of Veterinary Medicine Faculty of Veterinary MedicineUniversity of lbadanlbadan 200005Nigeria Faculty of Pharmaceutical Sciences University of JosPlateauJos 930003Nigeria

Recently,the potential role of vitamins in cancer therapy has attracted considerable research ***,the reported findings are inconsistent,with limited information on the biochemical and molecular interactions of different vitamins in various cancer ***,the presence of vitamin receptors in tumor cells suggests that vitamins play a significant role in the molecular and biochemical interactions in ***,studies on the efficacy of vitamin supplementation and dosage levels on tumor progression and mortality risk have yielded inconsistent ***,molecular and biochemical investigations have reported the function of vitamins in the proliferation,growth,and invasiveness of tumor cells,as well as in cell cycle arrest and inflammatory ***,different vitamins may regulate the cancer microenvironment by activating various molecular *** significantly affect immunological function,antioxidant defense,inflammation,and epigenetic control,and can improve treatment outcomes by affecting cell behavior and combating stress and DNA ***,further research is necessary to confirm the efficacy of vitamins,establish ideal dosages,and develop effective cancer prevention and treatment *** supplementation plans guided by medical knowledge are crucial to achieving optimal results in clinical and preclinical *** this review,we critically evaluated the effects of different vitamins on the risk and development of ***,we examined the potential of vitamin supplements to enhance the efficacy of drug therapy and counteract resistance mechanisms that often arise during cancer treatment.

关键词： Vitamins Cancer Biochemical Molecular interactions Therapy

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A retinoic acid:YAP1 signaling axis controls atrial lineage commitment

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Cell Reports 2025年第5期44卷 115687页

作者： Abraham, Elizabeth Kostina, Aleksandra Volmert, Brett Roule, Thomas Huang, Ling Yu, Jingting Williams, April E. Megill, Emily Douglas, Aidan Pericak, Olivia M. Morris, Alex Stronati, Eleonora Larrinaga-Zamanillo, Arantza Fueyo, Raquel Zubillaga, Mikel Andrake, Mark D. Akizu, Naiara Aguirre, Aitor Estaras, Conchi Department of Cardiovascular Sciences Aging + Cardiovascular Discovery Center Lewis Katz School of Medicine Temple University Philadelphia 19140 PA United States Institute for Quantitative Health Science and Engineering Division of Developmental and Stem Cell Biology Michigan State University East Lansing 48824 MI United States Department of Biomedical Engineering College of Engineering Michigan State University East Lansing 48824 MI United States Raymond G. Perelman Center for Cellular and Molecular Therapeutics The Children's Hospital of Philadelphia Philadelphia 19104 PA United States Integrative Genomics and Bioinformatics Core Salk Institute for Biological Studies La Jolla 92037 CA United States Department of Child and Adolescence Psychiatry The Children's Hospital of Philadelphia Philadelphia 19104 PA United States Department of Chemical and Systems Biology Stanford University School of Medicine Stanford 94305 CA United States Cancer Epigenetics Institute Fox Chase Cancer Center Philadelphia 19111 PA United States Molecular Modeling Facility Program in Cancer Signaling and Microenvironment Fox Chase Cancer Center Philadelphia 19111 PA United States

In cardiac progenitor cells (CPCs), retinoic acid (RA) signaling induces atrial lineage gene expression and acquisition of an atrial cell fate. To achieve this, RA coordinates a complex regulatory network of downstream effectors that is not fully identified. To address this gap, we applied a functional genomics approach (i.e., scRNA-seq and snATAC-seq) to untreated and RA-treated human embryonic stem cell (hESC)-derived CPCs. Unbiased analysis revealed that the Hippo effectors YAP1 and TEAD4 are integrated with the atrial transcription factor enhancer network and that YAP1 activates RA enhancers in CPCs. Furthermore, Yap1 deletion in mouse embryos compromises the expression of RA-induced genes, such as Nr2f2, in the CPCs of the second heart field. Accordingly, in hESC-derived patterned heart organoids, YAP1 regulates the formation of an atrial chamber but is dispensable for the formation of a ventricle. Overall, our findings revealed that YAP1 cooperates with RA signaling to induce atrial lineages during cardiogenesis. © 2025 The Author(s)

关键词： atrial differentiation cardiac enhancers cardiac progenitors chamber development CP: Developmental biology heart organoids NR2F2 retinoic acid signaling SHF TEAD4 YAP1

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Scientific discovery in the age of artificial intelligence

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NATURE 2023年第7978期621卷 E33-E33页

作者： Wang, Hanchen Fu, Tianfan Du, Yuanqi Gao, Wenhao Huang, Kexin Liu, Ziming Chandak, Payal Liu, Shengchao Van Katwyk, Peter Deac, Andreea Anandkumar, Anima Bergen, Karianne Gomes, Carla P. Ho, Shirley Kohli, Pushmeet Lasenby, Joan Leskovec, Jure Liu, Tie-Yan Manrai, Arjun Marks, Debora Ramsundar, Bharath Song, Le Sun, Jimeng Tang, Jian Velickovic, Petar Welling, Max Zhang, Linfeng Coley, Connor W. Bengio, Yoshua Zitnik, Marinka Department of Engineering University of Cambridge Cambridge UK Department of Computing and Mathematical Sciences California Institute of Technology Pasadena CA USA NVIDIA Santa Clara CA USA Department of Computational Science and Engineering Georgia Institute of Technology Atlanta GA USA Department of Computer Science Cornell University Ithaca NY USA Department of Chemical Engineering Massachusetts Institute of Technology Cambridge MA USA Department of Electrical Engineering and Computer Science Massachusetts Institute of Technology Cambridge MA USA Department of Computer Science Stanford University Stanford CA USA Department of Physics Massachusetts Institute of Technology Cambridge MA USA Harvard-MIT Program in Health Sciences and Technology Cambridge MA USA Mila – Quebec AI Institute Montreal Quebec Canada Université de Montréal Montreal Quebec Canada HEC Montréal Montreal Quebec Canada CIFAR AI Chair Toronto Ontario Canada Department of Earth Environmental and Planetary Sciences Brown University Providence RI USA Data Science Institute Brown University Providence RI USA Center for Computational Astrophysics Flatiron Institute New York NY USA Department of Astrophysical Sciences Princeton University Princeton NJ USA Department of Physics Carnegie Mellon University Pittsburgh PA USA Department of Physics and Center for Data Science New York University New York NY USA Google DeepMind London UK Department of Computer Science and Technology University of Cambridge Cambridge UK Microsoft Research Beijing China Department of Biomedical Informatics Harvard Medical School Boston MA USA Broad Institute of MIT and Harvard Cambridge MA USA Harvard Data Science Initiative Cambridge MA USA Kempner Institute for the Study of Natural and Artificial Intelligence Harvard University Cambridge MA USA Department of Systems Biology Harvard Medical School Boston MA USA Deep Forest Sciences Palo Alto CA USA BioMap Beijing China Mo

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Biologically-induced synthetic manganese carbonate precipitate (BISMCP) for potential applications in heavy metal removal

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Heliyon 2023年第5期9卷

作者： Dewi, Anggraeni Kumala Sharma, Raju Kumar Das, Koyeli Sukul, Uttara Lin, Pin-Yun Huang, Yi-Hsun Lu, Chung Ming Lu, Cheng-Kang Chen, Tsung-Hsien Chen, Chien-Yen Department of Physics National Chung Cheng University University Road Minhsiung Chiayi County 62102 Taiwan Doctoral Program in Science Technology Environment and Mathematics Department of Earth and Environmental Sciences National Chung Cheng University 168 University Road Min-Hsiung Chiayi County 62102 Taiwan Department of Chemistry and Biochemistry National Chung Cheng University 168 University Road Min-Hsiung Chiayi County 62102 Taiwan Department of Biomedical Sciences Graduate Institute of Molecular Biology National Chung Cheng University 168 University Road Min-Hsiung Chiayi County 62102 Taiwan Department of Chemical Engineering National Chung Cheng University University Road Minhsiung Chiayi County 62102 Taiwan Department of Chest Division Internal Medicine Ditmanson Medical Foundation Chiayi Christian Hospital 600566 Taiwan Department of Internal Medicine Ditmanson Medical Foundation Chiayi Christian Hospital 600566 Taiwan Center for Nano Bio-Detection Center for Innovative Research on Aging Society AIM-HI National Chung Cheng University 168 University Road Min-Hsiung Chiayi County 62102 Taiwan

Heavy metal pollution of water is a burning issue of today's world. Among several strategies involved for heavy metal remediation purpose, biomineralization has shown great potential. Of late, research has been focused on developing effective mineral adsorbents with reduced time and cost consumption. In this present paper, the Biologically-Induced Synthetic Manganese Carbonate Precipitate (BISMCP) was produced based on the biologically-induced mineralization method, employing Sporosarcina pasteurii in aqueous solutions containing urea and MnCl₂. The prepared adsorbent was characterized using Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), SEM-energy dispersive X-ray spectroscopy (SEM-EDX), X-ray diffraction (XRD) and BET surface area analyzer. EDX analysis showed the elements in the crystal BISMCP were Mn, C, and O. XRD result of BISMCP determined the crystal structure, which is close to rhodochrosite (MnCO₃). Spectral peaks of FTIR at 1641.79 cm⁻¹ confirmed the appearance of C[dbnd]O binding, with strong stretching of CO₃²⁻ in Amide I. From the six kinds of BISMCP produced, sample MCP-6 has the higher specific surface area by BET analysis at 109.01 m²/g, with pore size at 8.76 nm and higher pore volume at 0.178 cm³/g. These specifications will be suitable as an adsorbent for heavy metal removal by adsorption process. This study presents a preliminary analysis of the possibility of BISMCP for heavy metals adsorption using ICP multi-element standard solution XIII (As, Cr, Cd, Cu, Ni, and Zn). BISMCP formed from 0.1 MnCl₂ and 30 ml of bacteria volume (MCP-6) produced a better adsorbent material than others concentrations, with the adsorption efficiency of total As at 98.9%, Cr at 97.0%, Cu at 94.7%, Cd at 88.3%, Zn at 48.6%, and Ni at 29.5%. Future work could be examined its efficiency adsorbing individual heavy metals. © 2023

关键词： Adsorbent material Biologically induced mineralization Biomineralization Heavy metal removal Manganese carbonate (MnCO3) Sporosarcina pasteurii

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Interpretable network propagation with application to expanding the repertoire of human proteins that interact with SARS-CoV-2

arXiv

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arXiv 2020年

作者： Law, Jeffrey N. Akers, Kyle Tasnina, Nure Della Santina, Catherine M. Deutsch, Shay Kshirsagar, Meghana Klein-Seetharaman, Judith Crovella, Mark Rajagopalan, Padmavathy Kasif, Simon Murali, T.M. Interdisciplinary Ph.D. Program in Genetics Bioinformatics and Computational Biology BlacksburgVA United States Department of Computer Science Virginia Tech BlacksburgVA United States Department of Biomedical Engineering Boston University BostonMA United States Department of Mathematics University of California Los AngelesCA United States AI for Good Lab Microsoft RedmondWA United States Department of Chemistry Colorado School of Mines GoldenCO United States Department of Computer Science Boston University BostonMA United States Department of Chemical Engineering Virginia Tech BlacksburgVA United States

Background: Network propagation has been widely used for nearly 20 years to predict gene functions and phenotypes. Despite the popularity of this approach, little attention has been paid to the question of provenance tracing in this context, e.g., determining how much any experimental observation in the input contributes to the score of every prediction. Results: We design a network propagation framework with two novel components and apply it to predict human proteins that directly or indirectly interact with SARS-CoV-2 proteins. First, we trace the provenance of each prediction to its experimentally validated sources, which in our case are human proteins experimentally determined to interact with viral proteins. Second, we design a technique that helps to reduce the manual adjustment of parameters by users. We find that for every top-ranking prediction, the highest contribution to its score arises from a direct neighbor in a human protein-protein interaction network. We further analyze these results to develop functional insights on SARS-CoV-2 that expand on known biology such as the connection between endoplasmic reticulum stress, HSPA5, and anti-clotting agents. Conclusions: We examine how our provenance tracing method can be generalized to a broad class of network-based algorithms. We provide a useful resource for the SARS-CoV-2 community that implicates many previously undocumented proteins with putative functional relationships to viral infection. This resource includes potential drugs that can be opportunistically repositioned to target these proteins. We also discuss how our overall framework can be extended to other, newly-emerging viruses. © 2020, CC BY-NC-SA.

关键词： SARS

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Deep Nir-Ii Optical Imaging Combined with Minimally Invasive Interventional Photothermal Therapy for Orthotopic Bladder Cancer

SSRN

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SSRN 2022年

作者： Zhao, Qingliang Hong, Fengqiu Geng, Xiaorui Min, Guangzong Sun, Xiang Zhang, Bei Yao, Youliang Li, Ronghui Yuan, Zhen Wang, Jing Zhao, Hengyu Guo, Peng Wen, Xiaofei Nie, Liming Liu, Gang Chen, Xiaoyuan State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics Center for Molecular Imaging and Translational Medicine Department of Laboratory Medicine School of Public Health Xiamen University Xiamen361102 China Cancer Center Faculty of Health Sciences Centre for Cognitive and Brain Sciences University of Macau Macau Special Administrative Region Taipa999078 China College of Materials Xiamen University 422 Siming Nan Road Xiamen361005 China Shenzhen Research Institute of Xiamen University Shenzhen518063 China Department of medical oncology Xiang’an Hospital of Xiamen University 2000 East Xiang’an Rd. Xiang’an Xiamen361102 China Department of Radiology Xiamen Cardiovascular Hospital of Xiamen University School of Medcine Xiamen University Xiamen361102 China Capital Institute of Pediatrics Beijing100020 China Department of Interventional Radiology The First Affiliated Hospital of Xiamen University Fujian Xiamen361000 China The 4th Hospital of Harbin Medical University Heilongjiang Harbin150001 China Medical Research Center Guangdong Provincial People's Hospital Guangdong Academy of Medical Sciences Guangzhou510080 China Departments of Diagnostic Radiology Surgery Chemical and Biomolecular Engineering and Biomedical Engineering Yong Loo Lin School of Medicine Faculty of Engineering National University of Singapore Singapore119074 Singapore Clinical Imaging Research Centre Centre for Translational Medicine Yong Loo Lin School of Medicine National University of Singapore Singapore117599 Singapore Nanomedicine Translational Research Program NUS Center for Nanomedicine Yong Loo Lin School of Medicine National University of Singapore Singapore117597 Singapore

Surgical resection is the major method for treating invasive or recurrent noninvasive bladder cancer. However, SR still causes additional risks of urinary tract infection, bleeding and some complications that may be life-threatening. Therefore, it is of urgent need for new diagnosis and therapy scheme for BC. Herein, we proposed a strategy that combines dual-modality 3D NIR-II PA and OCTA molecular imaging to guide visually interventional PTT for BC. Additionally, we developed an excellent NIR-II hyaluronic acid-IR-1048 with liposome-coated (HAPO-1048) photothermal agent for PTT of CD44 overexpressing orthotopic BC, which showed strong NIR-II optical absorption, preferable tumor targeting, excellent biocompatibility and high PTT efficacy. Combined with the NIR-II PA response of the HAPO-1048, we can achieve high sensitivity and speciﬁcity (about 2 mm diameter) dynamic monitoring and investigate the therapeutic efficacy of PTT at larger penetration depth (4.38 mm under the tissue) in orthotopic BC. Simultaneously, we can map the dynamic changes of 3D PA signals and HAPO-1048 NPs enrichment, which is closely related to the PTT efficacy. Significantly, the whole changes of complex microvascular morphometrics and angiogenesis of BC were well surveilled and assessed in vivo using OCTA. Lastly, minimally invasive interventional PTT strategy was implemented to achieve a controllable and precise therapy for BC based on laparoscopy and US guidance. In conclusion, we present a multimodal NIR-II optical imaging synergy laparoscopy interventional scheme, which should expand the current PTT technology, leading to a significant ongoing in treatment of primary tumors of urinary system. © 2022, The Authors. All rights reserved.

关键词： Infrared devices

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Genetically programmable Fusion Cellular Vesicles for Cancer Immunotherapy

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Angewandte Chemie 2021年第50期133卷

作者： Dr. Qian-Fang Meng Yuyue Zhao Dr. Chunbo Dong Dr. Lujie Liu Dr. Yuanwei Pan Jialin Lai Prof. Zhida Liu Prof. Guang-Tao Yu Prof. Xiaoyuan Chen Prof. Lang Rao Institute of Biomedical Health Technology and Engineering Shenzhen Bay Laboratory Shenzhen 518132 China Stomatological Hospital Southern Medical University Guangzhou 510280 China Shanxi Academy of Advanced Research and Innovation Taiyuan 030032 China Departments of Diagnostic Radiology Surgery Chemical and Biomolecular Engineering and Biomedical Engineering Yong Loo Lin School of Medicine and Faculty of Engineering National University of Singapore Singapore 119074 Singapore Clinical Imaging Research Centre Centre for Translational Medicine Yong Loo Lin School of Medicine National University of Singapore Singapore 117599 Singapore Nanomedicine Translational Research Program NUS Center for Nanomedicine Yong Loo Lin School of Medicine National University of Singapore Singapore 117597 Singapore

Herein, we report that genetically programmable fusion cellular vesicles (Fus-CVs) displaying high-affinity SIRPα variants and PD-1 can activate potent antitumor immunity through both innate and adaptive immune effectors. Dual-blockade of CD47 and PD-L1 with Fus-CVs significantly increases the phagocytosis of cancer cells by macrophages, promotes antigen presentation, and activates antitumor T-cell immunity. Moreover, the bispecific targeting design of Fus-CVs ensures better targeting on tumor cells, but less on other cells, which reduces systemic side effects and enhances therapeutic efficacies. In malignant melanoma and mammary carcinoma models, we demonstrate that Fus-CVs significantly improve overall survival of model animals by inhibiting post-surgery tumor recurrence and metastasis. The Fus-CVs are suitable for protein display by genetic engineering. These advantages, integrated with other unique properties inherited from source cells, make Fus-CVs an attractive platform for multi-targeting immune checkpoint blockade therapy.

关键词： CD47/SIRPα cell membrane nanoparticle genetic engineering immune checkpoint therapy PD-1/PD-L1

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