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Carrier-free nanodrugs for stemness inhibition-enhanced photodynamic therapy

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聚集体(英文)

聚集体(英文) 2023年第3期4卷 84-93页

作者： Yuwei Liu Kaiqi Long Tianyi Wang Weirong Kang Weiping Wang State Key Laboratory of Pharmaceutical Biotechnology The University of Hong KongHong KongChina Department of Pharmacology and Pharmacy Li Ka Shing Faculty of MedicineThe University of Hong KongHong KongChina Laboratory of Molecular Engineering and Nanomedicine Dr.Li Dak-Sum Research CentreThe University of Hong KongHong KongChina

Cancer stem cell(CSC)has been considered a key driver of tumor growth,recurrence,and metastasis due to its self-renewal and tumor initiation capacities called *** is also responsible for the high resistance of CSC to current therapeutic strategies,including photodynamic therapy(PDT)and *** this study,a carrier-free nanodrug(designated as MKCe6 nanoparticle[NP])selfassembled by photosensitizer chlorin e6(Ce6)and stemness inhibitor MK-0752 was prepared for effective tumor *** inhibition caused by MK-0752 could sensitize CSCs to *** from the high drug-loading capacity and efficient cellular internalization,MKCe6 NPs exhibited good performance in PDT and stemness *** this way,effective tumor growth repression and tumorigenesis inhibition by MKCe6 NPs were observed both in vitro and in *** self-delivery nanodrug for stemness inhibition-enhanced photodynamic therapy may provide new insights for clinical cancer therapy.

关键词： cancer stemness nanomedicine Notch pathway photodynamic therapy self-assembly

Light-responsive nanomedicine for cancer immunotherapy

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药学学报:英文版 2023年第6期13卷 2346-2368页

作者： Weirong Kang Yuwei Liu Weiping Wang State Key Laboratory of Pharmaceutical Biotechnology the University of Hong KongHong KongChina Department of Pharmacology and Pharmacy Li Ka Shing Faculty of Medicinethe University of Hong KongHong KongChina Laboratory of Molecular Engineering and Nanomedicine Dr.Li Dak-Sum Research Centrethe University of Hong KongHong KongChina

Immunotherapy emerged as a paradigm shift in cancer treatments, which can effectively inhibit cancer progression by activating the immune system. Remarkable clinical outcomes have been achieved through recent advances in cancer immunotherapy, including checkpoint blockades, adoptive cellular therapy, cancer vaccine, and tumor microenvironment modulation. However, extending the application of immunotherapy in cancer patients has been limited by the low response rate and side effects such as autoimmune toxicities. With great progress being made in nanotechnology, nanomedicine has been exploited to overcome biological barriers for drug delivery. Given the spatiotemporal control,light-responsive nanomedicine is of great interest in designing precise modality for cancer immunotherapy. Herein, we summarized current research utilizing light-responsive nanoplatforms to enhance checkpoint blockade immunotherapy, facilitate targeted delivery of cancer vaccines, activate immune cell functions, and modulate tumor microenvironment. The clinical translation potential of those designs is highlighted and challenges for the next breakthrough in cancer immunotherapy are discussed.

关键词： Light-responsive nanoparticles Photodynamic therapy Photothermal therapy Nanomedicine Cancer therapy Immunotherapy Photopharmacology Light-triggered drug release

A near-infrared plasma membrane-specific AIE probe for fluorescence lifetime imaging of phagocytosis

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Science China Chemistry 2022年第5期65卷 979-988页

作者： ming-Yu Wu Jong-Kai Leung Chuen Kam Tsu Yu Chou Jia-Li Wang Xueqian Zhao Shun Feng Sijie Chen ming wai lau centre for reparative medicine Karolinska InstitutetHong KongChina Sichuan Engineering Research Center for Biomimetic Synthesis of Natural Drugs School of Life Science and EngineeringSouthwest Jiaotong UniversityChengdu 610031China

Phagocytosis is a biological process that plays a key role in host defense and tissue *** approaches for real-time imaging of phagocytosis are highly desired but ***,an AIE-active near-infrared fluorescent probe,named TBTCP,was developed for fluorescence lifetime imaging of *** could selectively label the cell plasma membrane with fast staining,wash-free process,high signal-to-background ratio,and excellent *** membrane statuses under different osmolarities as well as macrophage phagocytosis of bacteria or large silica particles in early stages could be reported by the fluorescence lifetime changes of *** with current fluorescence imaging methods,which target the bioenvironmental changes in the late phagocytosis stage,this approach detects the changes in the cell membrane,thus giving a faster response to *** article provides a functional tool to report the phagocytic dynamics of macrophages which may greatly contribute to the studies of phagocytic function-related diseases.

关键词： fluorescence lifetime imaging phagocytosis plasma membrane aggregation-induced emission near-infrared

An AIE-active probe for efficient detection and high-throughput identification of outer membrane vesicles

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聚集体(英文)

聚集体(英文) 2023年第4期4卷 111-121页

作者： Fei Wang Po-Yu Ho Chuen Kam Quanzhi Yang Jinzhao Liu Weiping Wang Engui Zhao Sijie Chen ming wai lau centre for reparative medicine Karolinska InstitutetHong KongP.R.China Laboratory of Molecular Engineering and Nanomedicine Dr.Li Dak-Sum Research CentreThe University of Hong KongHong KongP.R.China School of Science Harbin Institute of TechnologyShenzhenHIT Campus of University TownShenzhenGuangdongP.R.China

Rapid detection and quantification of outer membrane vesicle(OMV)are of both scientific value and clinical ***,limited tools are available for investigations of ***,we report a novel fluorescent probe with aggregation-induced emission(AIE)characteristics,namely,OEO-TPE-MEM(OTM),for OMV *** emits faintly in an aqueous medium,but its fluorescence could be effectively turned on upon interacting with bacteria bodies and OMVs produced by Gram-negative ***,OTM could provide quantitative information on bacterial membrane remodeling and OMV secretion and be applied to high-throughput screening of OMV-inducing *** study presents a powerful AIE probe for imaging and quantitative analysis of bacteria envelop and derived OMVs,which might be applied for evaluating research and clinical antimicrobial materials in future studies.

关键词： aggregation-induced emission antibiotics bacteria fluorescent probe outer membrane vesicle

A Highly Efficient Aggregation-induced Emission Photosensitizer for Photodynamic Combat of Multidrug-resistant Bacteria

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Chemical Research in Chinese Universities 2021年第1期37卷 150-156页

作者： ZOU Qian WANG Jia-Li WU ming-Yu KAM LEE Sin-Ying FENG Shun CHEN Sijie School of Life Science and Engineering Southwest Jiaotong UniversityChengdu610031P.R.China ming wai lau centre for reparative medicine Karolinska InstitutetHong KongP.R.China

With the antibiotic abuse and the resulting increased antibiotic resistance,the bacterial infection has posed a serious threat to human *** therapy is an effective tool for treating localized and superficial *** is a promising approach for the treatment of superbugs and with minimal risk of induced antibiotic ***,an isoquinolinium-based photosensitizer,LIQ-TPE,with aggregation-induced emission properties is designed and *** is with high 1O2 generation efficiency and shows efficient antibacterial performance towards both Gram-negative and Gram-positive bacteria,and even methicillin-resistant Staphylococcus aureus(MRSA).LIQ-TPE thus shows great promise as an effective antimicrobial agent to combat the menace of multi-drug resistant bacteria.

关键词： Aggregation-induced emission Photosensitizer Isoquinolinium Photodynamic antibiosis

Taming Reactive Oxygen Species:Mitochondria-Targeting Aggregation-Induced Emission Luminogen for Neuron Protection via Photosensitization-Triggered Autophagy

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CCS Chemistry 2022年第7期4卷 2249-2257页

作者： Chao Chen Ruoyao Zhang Jianyu Zhang Yufan Zhang Haoke Zhang Zaiyu Wang Xiaolin Huang Sijie Chen Ryan T.K.Kwok Jacky W.Y.Lam Dan Ding Ben Zhong Tang Department of Chemistry Hong Kong Branch of Chinese National Engineering Research Center for Tissue Restoration and ReconstructionInstitute for Advanced StudyState Key Laboratory of Molecular NanoscienceDivision of Life ScienceDepartment of Chemical and Biological EngineeringThe Hong Kong University of Science and TechnologyClear Water BayKowloonHong Kong 999077 State Key Laboratory ofMedicinal Chemical Biology Key Laboratory of Bioactive MaterialsMinistry of EducationCollege of Life SciencesNankai UniversityTianjin 300071 ming wai lau centre for reparative medicine Karolinska InstitutetHong Kong 999077 Center for Aggregation-Induced Emission SCUT-HKUST Joint Research InstituteState Key Laboratory of Luminescent Materials and DevicesSouth China University of TechnologyGuangzhou 510640 Shenzhen Institute of Aggregate Science and Technology School of Science and EngineeringThe Chinese University of Hong KongShenzhen 518172 AIE Institute Guangzhou Development DistrictHuangpuGuangzhou 510530

Oxidative damage to cells leads to accumulated harmful wastes,which in turn aggravate the imbalance of reactive oxygen species(ROS)and related ***,provoking the cellular defense system against severe oxidation and maintaining ROS homeostasis are ***,we designed and synthesized a powerful mitochondria-targeting aggregation-induced emission photosensitizer(named DTCSPY)by maximal restriction of heat *** is demonstrated that taming ROS generation within mitochondria through photosensitization-triggered autophagy via DTCSPY achieved a better neuroprotective effect against oxidative damages than Nacety-L-cysteine and vitamin *** work not only provides a new way to design high-performance photosensitizers by regulating the photophysical property,but also verifies the concept that taming ROS can be used for cell protection against destructive oxidation,thereby displaying broad prospects for alleviating oxidation-related diseases and promoting cell-based therapy.

关键词： aggregation-induced emission mitochondrial targeting photosensitizer reactive oxygen species neuron protection

Mechanistic connotations of restriction of intramolecular motions(RIM)

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National Science Review 2021年第6期8卷 10-13页

作者： Yujie Tu Zheng Zhao Jacky W.Y.Lam Ben Zhong Tang Department of Chemistry Hong Kong Branch of Chinese National Engineering Research Center for Tissue Restoration and ReconstructionInstitute for Advanced Study and Department of Chemical and Biological EngineeringThe Hong Kong University of Science and Technology Center for Aggregation-Induced Emission SCUT-HKUST Joint Research InstituteState Key Laboratory of Luminescent Materials and DevicesSouth China University of Technology AIE Institute Guangzhou Development District ming wai lau centre for reparative medicine Karolinska Institutet

Molecules are all in constant motions,which influence their properties. For example, in photophysics, the light emission behavior of a luminogen is determined by its electronic and nuclear motions in the excited state. Flexible molecular motions usually favor nonradiative decay along with the transformation of excited-state energy to other forms such as thermal energy. Therefore,the restriction of intramolecular motions(RIM) is commonly adopted to achieve luminescent materials with high emission brightness.

关键词： AGGREGATION-INDUCED EMISSION CONICAL INTERSECTION

Photo-triggered nucleus targeting for cancer drug delivery

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Nano Research 2021年第8期14卷 2630-2636页

作者： Yafei Li Wen Lv Lang Wang Yarning Zhang Lipeng Yang Tianyi Wang Linyong Zhu Yufeng Wang Weiping Wang Department of Pharmacology and Pharmacy Li Ka Shing Faculty of MedicineThe University of Hong KongHong KongChina Dr.Li Dak-Sum Research centre The University of Hong KongHong KongChina Department of Chemistry The University of Hong Kong Hong Kong China School of Chemistry and Molecular Engineering East China University of Science and Technology Shanghai 200030China

Here,we report a strategy to deliver drug nanoparticles into cells with nucleus-targeting ability under a spatiotemporal *** nanoparticles were constructed through self-assembly of photoresponsive prodrugs and free *** incorporating a nucleus localization sequence in the system,drug nanoparticles could be delivered into nuclei upon visible light *** drug nanoparticles showed high drug loading capacity and specific nucleus-targeting ability,which efficiently killed cancer *** self-assembly strategy could be applied to other hydrophobic drugs and targeting ligands for photo-controlled organelle-targeted drug delivery.

关键词： phototargeting dePEGylation nucleus targeting coumarin photoresponsive prodrugs