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Tumor microenvironment responsive nano-PROTAC for BRD4 degradation enhanced cancer photo-immunotherapy

Biomaterials 2025年 322卷 123387-123387页

作者： Li, Zheng Ren, Guodong Wang, Xuewei Li, Xiaowan Ding, Lingwen Zhu, Jianwei Zhang, Yajie Zhang, Chengwu Zou, Jianhua Chen, Xiaoyuan Departments of Diagnostic Radiology 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 School of Basic Medical Sciences Shanxi Medical University Taiyuan030001 China 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 Yong Loo Lin School of Medicine National University of Singapore Singapore 117597 Singapore Yong Loo Lin School of Medicine National University of Singapore 11 Biopolis Way Helios Singapore 138667 Singapore 61 Biopolis Drive Proteos Singapore 138673 Singapore Department of Pharmacy and Pharmaceutical Sciences National University of Singapore Lower Kent Ridge Road 4 Science Drive 2 117544 Singapore

Proteolysis Targeting Chimeras (PROTAC) technology has garnered great attention due to its advantages in targeted protein degradation, promising its potential for treating malignant cancer. Nevertheless, the inherent drawbacks of PROTAC technology hinder its clinical translation. The integration of nanotechnology with PROTAC molecules to create nano-PROTACs for combined therapy offers a promising solution. Among the various cancer treatment methods, phototherapy is considered the optimal choice to integrate with specific PROTACs due to its proven effectiveness and non-invasive nature. Herein, a nano-PROTAC formulation (ARV@PEG-ICG) consisting of a phototherapeutic agent named indocyanine green functionalized polyethylene glycol (PEG-ICG) and a BRD4 degrader (ARV-825) was fabricated for cancer photo-immunotherapy. Activated by acidic tumor microenvironment (TME), ARV@PEG-ICG nanoparticles (NPs) will decompose rapidly for ARV delivery. PEG-ICG generated abundant ROS with laser irradiation, downregulating the expression of Bcl-xL and inducing the cleavage of PARP to stimulate cell apoptosis. Furthermore, the degradation of BRD4, a transcriptional cofactor, inhibited nitric oxide synthase (iNOS) generation to improve phototherapeutic efficacy. In a 4T1 breast tumor model, dying 4T1 cells released tumor associated antigens (TAAs) to serve as the immunogenic cell death (ICD) inducer, facilitating DC maturation and T cell activation and amplifying systemic immune response. The distant tumor growth can also be inhibited due to the activation of long-term immune response. Overall, the current study aims to combine typical PROTAC with functional nanomaterials to form nano-PROTAC with high performance for PROTAC delivery mediated cancer treatment. © 2025 Elsevier Ltd

关键词： Nanocomposites

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A hypoxia-activated copper ion nanoexchanger for cancer immunotherapy by in situ precise production of immunogenic cell death inducer

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Chinese chemical Letters 2025年

作者： Xinlu Zhang Yongxin Liu Huan Li Shutong Chen Guocheng Wang Xu Zhang Chen Cao Xiaoyuan Chen Sheng Wang School of Life Sciences Faculty of Medicine Tianjin University Tianjin 300072 China Department of Diagnostic Radiology Yong Loo Lin School of Medicine National University of Singapore Singapore 119074 Singapore Department of Chemical and Biomolecular Engineering College of Design and Engineering National University of Singapore Singapore 117575 Singapore Department of Biomedical Engineering College of Design and Engineering National University of Singapore Singapore 117575 Singapore Department of Pharmacy and Pharmaceutical Sciences Faculty of Science National University of Singapore Singapore 117544 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 Yong Loo Lin School of Medicine National University of Singapore Singapore 117597 Singapore Theranostics Center of Excellence (TCE) Yong Loo Lin School of Medicine National University of Singapore Singapore 138667 Singapore Institute of Molecular and Cell Biology Agency for Science Technology and Research (A*STAR) Singapore 138673 Singapore

In situ therapeutic agent production strategy is promising to overcome the drawbacks of direct drug delivery. Hypoxia provides a great target for precise treatment of tumor. Here we report a copper ion competition-based nanoparticle (NP) for hypoxia-activated formation of diethyldithiocarbamate (DTC)-copper complex, an immunogenic cell death (ICD) inducer. The NP is composed of an amphiphilic hypoxia-responsive DTC precursor and a fluorescence quenched copper ion-chelated squaric acid. In hypoxic tumor cells, the azobenzene linker in DTC precursor can be cleaved through bioreduction, leading to DTC release and subsequent copper ion exchange between DTC and squaric acid. Simultaneous formation of toxic DTC-copper complexes and fluorescence recovery will allow for visualization of in situ therapeutic agents production. Furthermore, the DTC-copper complexes can induce ICD and promote cytotoxic T lymphocyte infiltration for cancer immunotherapy. This study not only provides a promising hypoxia-activated nanomedicine for precision cancer therapy, but also a visualization strategy for evaluating the treatment process.

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Self-Assembled Fluorescent Peptide Nanoprobes for Disease Diagnosis

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Small methods 2025年 e2500518页

作者： Ruichen Wang Tianwen Xi Kaixuan Li Chenyang Wang Xing Gao Hui Yang Jianhua Zou Xiaoyuan Chen Leming Sun School of Life Sciences Engineering Research Center of Chinese Ministry of Education for Biological Diagnosis Northwestern Polytechnical University Shaanxi Xi'an 710072 China. Innovation Center NPU Chongqing Northwestern Polytechnical University Chongqing 400000 China. Department of Diagnostic Radiology Yong Loo Lin School of Medicine National University of Singapore Singapore 119074 Singapore. Nanomedicine Translational Research Program NUS Center for Nanomedicine Yong Loo Lin School of Medicine National University of Singapore Singapore 117597 Singapore. Department of Chemical and Biomolecular Engineering College of Design and Engineering National University of Singapore Singapore 117575 Singapore. Department of Biomedical Engineering College of Design and Engineering National University of Singapore Singapore 117575 Singapore. Department of Pharmacy and Pharmaceutical Sciences Faculty of Science National University of Singapore Singapore 117544 Singapore. Clinical Imaging Research Centre Centre for Translational Medicine Yong Loo Lin School of Medicine National University of Singapore Singapore 117599 Singapore. Theranostics Center of Excellence (TCE) Yong Loo Lin School of Medicine National University of Singapore Singapore 138667 Singapore.

Benefiting from the advantages of simple reactions, low energy consumption, and uniform properties, self-assembly has been widely utilized for preparation of nanoprobes. Peptides have been chosen as "bricks" for self-assembling nano-biomaterials due to their easy drug formation, highly variable sequence, good biocompatibility and biodegradability. Peptides can efficiently self-assemble through noncovalent interactions, such as hydrogen bonding, electrostatic interactions, π-π stacking, hydrophobic interactions, and van der Waals forces. Based on this, many ex situ and in situ self-assembly strategies are developed. The former self-assembles into stable nanomaterials beforehand, while the latter undergoes in situ self-assembly at the target site in response to its specific stimulus-responsive modules. As probe sizes are miniaturized to the nanometer scale, they gain high sensitivity, low detection limits, and the capability for in situ detection. Nanoprobes created through self-assembly, usually possess targeted accumulation in specific tissues, prolonged elimination half-life, and multimodal imaging capabilities, making them highly effective for disease diagnosis. This review introduces the types of self-assembled fluorescent peptide nanoprobes according to the source of fluorescence properties and summarizes the progress of their application in disease diagnosis, such as cancer, neurodegenerative disease, and bacterial infection. In addition, their limitations will be discussed, and new strategies will be proposed for the development of advanced peptide-based fluorescent self-assembling nanoprobes, aimed at improving their potential for clinical translation.

关键词： disease diagnosis fluorescent nanoprobes peptide self‐assembly

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Phage therapy

NATURE REVIEWS METHODS PRIMERS

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NATURE REVIEWS METHODS PRIMERS 2025年第1期5卷 1页

作者： [Anonymous] Human Microbiome Research Program Department of Bacteriology and Immunology Faculty of Medicine University of Helsinki Helsinki Finland European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Study Group for Non-traditional Antibacterial Therapy (ESGNTA) Basel Switzerland Institute of Biomedical and Oral Research (IBOR) Faculty of Dental Medicine Hebrew University of Jerusaleum Jerusalem Israel The Israeli Phage Center (IPTC) of the Hebrew University and Hadassah Medical Center Jerusalem Israel Department of Clinical Microbiology and Infectious Diseases Hadassah–Hebrew University Medical Center Jerusalem Jerusalem Israel Laboratory of Gene Technology Department of Biosystems KU Leuven Leuven Belgium Leicester Centre for Phage Research Department of Genetics and Genome Biology University of Leicester Leicester UK Center for Evolutionary Hologenomics Globe Institute University of Copenhagen Copenhagen Denmark Centre of Excellence for Omics-Driven Computational Biodiscovery (COMBio) AIMST University Bedong Kedah Malaysia Laboratory of Phage Molecular Biology Institute of Immunology and Experimental Therapy Wrocław Poland Wrocław University of Science and Technology Faculty of Medicine Wrocław Poland Department of Biological Sciences University of Pittsburgh Pittsburgh PA USA Laboratory for Molecular and Cellular Technology Queen Astrid Military Hospital Brussels Belgium Department of Biological and Environmental Science Nanoscience Center University of Jyväskylä Jyväskylä Finland Chemical Engineering Department Loughborough University Loughborough UK

Bacteriophage (phages) are viruses that exclusively use bacterial cells for propagation, killing the bacterial host in the process. In phage therapy, phages are used to reduce bacterial numbers, thereby curing bacterial infections. Although this principle is conceptually straightforward, its practical application faces several hurdles. In this Primer, the practical aspects of phage therapy are outlined. We introduce the microbiological methods used to prepare and characterize phages and elucidate their interactions with bacteria. The discussion covers how the information in complete phage genome sequences is used, along with how RNA sequencing can enhance our understanding of phage biology. Selection parameters for therapeutic phages for clinical applications and key elements in industrial-scale phage production are provided. A summary of clinical trials both past and present, phage administration and dosing issues is analysed, as well as limitations associated with phage therapy and mitigation strategies. Finally, we speculate on the future of phage therapy.

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Thermo- and Mechanochromic Camouflage and Self-Healing in Biomimetic Soft Actuators Based on Liquid Crystal Elastomers

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Angewandte Chemie 2021年第8期134卷

作者： Zhongcheng Liu Dr. Hari Krishna Bisoyi Yinliang Huang Meng Wang Prof. Hong Yang Prof. Quan Li Institute of Advanced Materials School of Chemistry and Chemical Engineering and Jiangsu Province Hi-Tech Key Laboratory for Biomedical Research Southeast University Nanjing 211189 China Advanced Materials and Liquid Crystal Institute and Chemical Physics Interdisciplinary Program Kent State University Kent OH 44242 USA

In nature, many mysterious creatures capable of deformation camouflage, color camouflage, and self-healing have inspired scientists to develop various biomimetic soft robots. However, the systematic integration of all the above functionalities into a single soft actuator system still remains a challenge. Here we chemically introduce a multi-stimuli-responsive tetraarylsuccinonitrile (TASN) chromophore into a liquid crystal elastomer (LCE) network through a facile thiol-ene photoaddition method. The obtained TASN-LCE soft actuators not only exhibit reversible shape-morphing and reversible color-changing behavior in response to heat and mechanical compression, but also show excellent self-healing, reprogramming and recycling characteristics. We hope that such a TASN-LCE actuator system endowed with dynamic distortion, thermo- and mechano-chromic camouflage, and self-healing functionalities would pave the way for further development of multifunctional biomimetic soft robotic devices.

关键词： Biomimetic actuator Camouflage Chromophore Liquid crystal elastomer Self-healing

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Activatable NIR-II Photothermal Lipid Nanoparticles for Improved Messenger RNA Delivery

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Angewandte Chemie 2023年第25期135卷

作者： Dr. Benhao Li Dr. Mengyao Zhao Weiping Lai Dr. Xuanbo Zhang Bowei Yang Prof. Xiaoyuan Chen Prof. Qianqian Ni 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 Nanomedicine Translational Research Program NUS Centre for Nanomedicine Yong Loo Lin School of Medicine National University of Singapore Singapore 117597 Singapore Contribution: Investigation (lead) Writing - original draft (lead) Contribution: Investigation (supporting) Department of Chemistry State Key Laboratory of Molecular Engineering of Polymers and iChem Shanghai Key Laboratory of Molecular Catalysis and Innovative Material Fudan University Shanghai 200433 China Clinical Imaging Research Centre Centre for Translational Medicine Yong Loo Lin School of Medicine National University of Singapore Singapore 117599 Singapore Institute of Molecular and Cell Biology Agency for Science Technology and Research (A*STAR) Singapore 138673 Singapore Contribution: Funding acquisition (equal) Supervision (equal) Writing - review & editing (equal)

Endosomal escape remains a central issue limiting the high protein expression of mRNA therapeutics. Here, we present second near-infrared (NIR-II) lipid nanoparticles (LNPs) containing pH activatable NIR-II dye conjugated lipid (Cy-lipid) for potentiating mRNA delivery efficiency via a s timulus-responsive p hotothermal-promoted e ndosomal e scape d elivery (SPEED) strategy. In acidic endosomal microenvironment, Cy-lipid is protonated and turns on NIR-II absorption for light-to-heat transduction mediated by 1064 nm laser irradiation. Then, the heat-promoted LNPs morphology change triggers rapid escape of NIR-II LNPs from the endosome, allowing about 3-fold enhancement of enhanced green fluorescent protein (eGFP) encoding mRNA translation capacity compared to the NIR-II light free group. In addition, the bioluminescence intensity induced by delivered luciferase encoding mRNA in the mouse liver region shows positive correlation with incremental radiation dose, indicating the validity of the SPEED strategy.

关键词： Endosomal Escape Lipid Nanoparticle Photothermal Effect Second Near-Infrared Window

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Transformative and sustainable insights of agricultural waste-based adsorbents for water defluoridation: Biosorption dynamics, economic viability, and spent adsorbent management

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Heliyon 2024年第8期10卷 e29747页

作者： Das, Koyeli Sukul, Uttara Chen, Jung-Sheng Sharma, Raju Kumar Banerjee, Pritam Dey, Gobinda Taharia, Md. Wijaya, Christian J. Lee, Cheng-I Wang, Shan-Li Nuong, Nguyen Hoang Kim Chen, Chien-Yen Department of Biomedical Sciences Graduate Institute of Molecular Biology National Chung Cheng University 168 University Road Min-Hsiung 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 Medical Research E-Da Hospital Kaohsiung 82445 Taiwan Department of Chemistry and Biochemistry National Chung Cheng University 168 University Road Min-Hsiung Chiayi County 62102 Taiwan Department of Chemical Engineering Widya Mandala Surabaya Catholic University Kalijudan 37 Surbaya 60114 Indonesia Collaborative Research Center for Zero Waste and Sustainability Kalijudan 37 Surabaya 60114 Indonesia 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 Department of Agricultural Chemistry National Taiwan University Taipei 106319 Taiwan

With the progression of civilization, the harmony within nature has been disrupted, giving rise to various ecocidal activities that are evident in every spheres of the earth. These activities have had a profound and far-reaching impact on global health. One significant example of this is the presence of fluoride in groundwater exceeding acceptable limits, resulting in the widespread occurrence of “Fluorosis” worldwide. It is imperative to mitigate the concentration of fluoride in drinking water to meet safety standards. While various defluoridation techniques exist, they often have drawbacks. Biosorption, being a simple, affordable and eco-friendly method, has gained preference for defluoridation. However, its limited commercialization underscores the pressing need for further research in this domain. This comprehensive review article offers a thorough examination of the defluoridation potential of agro-based adsorbents, encompassing their specific chemical compositions and preparation methods. The review presents an in-depth discussion of the factors influencing fluoride biosorption and conducts a detailed exploration of adsorption isotherm and adsorption kinetic models to gain a comprehensive understanding of the nature of the adsorption process. Furthermore, it evaluates the commercial viability through an assessment of regeneration potential and a cost analysis of these agro-adsorbents, with the aim of facilitating the scalability of the defluoridation process. The elucidation of the adsorption mechanism and recommendations for overcoming challenges in large-scale implementation offer a comprehensive outlook on this eco-friendly and sustainable approach to fluoride removal. In summary, this review article equips readers with a lucid understanding of agro-adsorbents, elucidates their ideal conditions for improved performance, offers a more profound insight into the fluoride biosorption mechanism, and introduces the concept of effective spent adsorbent management.

关键词： Adsorption mechanism Agricultural waste Bio-sorption Cost analysis Defluoridation Regeneration Spent adsorbent management

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Inside Back Cover: Irradiation-Wavelength Directing Circularly Polarized Luminescence in Self-Organized Helical Superstructures Enabled by Hydrogen-Bonded Chiral Fluorescent Molecular Switches (Angew. Chem. Int. Ed. 52/2021)

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Angewandte Chemie International Edition 2021年第52期60卷

作者： Yanrong He Dr. Shu Zhang Dr. Hari Krishna Bisoyi Jinghui Qiao Hong Chen JingJing Gao Prof. Jinbao Guo Prof. Quan Li Key Laboratory of Carbon Fibers and Functional Polymers Ministry of Education College of Materials Science and Engineering Beijing University of Chemical Technology Beijing 100029 China Institute of Advanced Materials School of Chemistry and Chemical Engineering Jiangsu Province Hi-Tech Key Laboratory for Biomedical Research Southeast University Nanjing 211189 China Advanced Materials and Liquid Crystal Institute and Chemical Physics Interdisciplinary Program Kent State University Kent Ohio 44242 USA

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Irradiation-Wavelength Directing Circularly Polarized Luminescence in Self-Organized Helical Superstructures Enabled by Hydrogen-Bonded Chiral Fluorescent Molecular Switches

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Angewandte Chemie 2021年第52期133卷

Two light-driven chiral fluorescent molecular switches, ( R , S , R )-switch 1 and ( R , S , R )-switch 2 , are prepared by means of hydrogen-bonded (H-bonded) assembly of a photoresponsive ( S ) chiral fluorescent molecule, respectively with a cyano substitution at different positions as an H-bond acceptor and an opposite ( R ) chiral molecule as an H-bond donor. The resulting two switches exhibit tunable and reversible Z / E photoisomerization irradiated with 450 nm blue and 365 nm UV light. When doped into an achiral liquid crystal, both switches are found to be able to form a CPL tunable luminescent helical superstructure. In contrast to the tunable CPL characteristics of the system incorporating switch 2 , exposure of the system incorporating switch 1 to 365 nm and 450 nm radiation can lead to controllable different photostationary CPL behavior, including switching-off and polarization inversion. In addition, optical information coding is demonstrated using the system containing switch 1 .

关键词： circularly polarized luminescence handedness inversion hydrogen-bonded chiral fluorescent switch luminescent helical superstructures

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Innenrücktitelbild: Irradiation-Wavelength Directing Circularly Polarized Luminescence in Self-Organized Helical Superstructures Enabled by Hydrogen-Bonded Chiral Fluorescent Molecular Switches (Angew. Chem. 52/2021)

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Angewandte Chemie 2021年第52期133卷

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