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tumor necrosis factor-stimulated gene-6 ameliorates early brain injury after subarachnoid hemorrhage by suppressing NLRC4 inflammasome-mediated astrocyte pyroptosis

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Neural Regeneration Research 2024年第5期19卷 1064-1071页

作者： Mingxiang Ding Lei Jin Boyang Wei Wenping Cheng Wenchao Liu Xifeng Li Chuanzhi Duan Neurosurgery Center Department of Cerebrovascular SurgeryThe National Key Clinical SpecialtyThe Engineering Technology Research Center of Education Ministry of China on Diagnosis and Treatment of Cerebrovascular DiseaseGuangdong Provincial Key Laboratory on Brain Function Repair and RegenerationThe Neurosurgery Institute of Guangdong ProvinceZhujiang HospitalSouthern Medical UniversityGuangzhouGuangdong ProvinceChina department of Cerebrovascular Intervention Zhongshan City People’s HospitalZhongshanGuangdong ProvinceChina

Subarachnoid hemorrhage is associated with high morbidity and mortality and lacks effective *** is a crucial mechanism underlying early brain injury after subarachnoid *** studies have confirmed that tumor necrosis factor-stimulated gene-6(TSG-6)can exert a neuroprotective effect by suppressing oxidative stress and ***,no study to date has explored whether TSG-6 can alleviate pyroptosis in early brain injury after subarachnoid *** this study,a C57BL/6J mouse model of subarachnoid hemorrhage was established using the endovascular perforation *** results indicated that TSG-6 expression was predominantly detected in astrocytes,along with NLRC4 and gasdermin-D(GSDMD).The expression of NLRC4,GSDMD and its N-terminal domain(GSDMD-N),and cleaved caspase-1 was significantly enhanced after subarachnoid hemorrhage and accompanied by brain edema and neurological *** explore how TSG-6 affects pyroptosis during early brain injury after subarachnoid hemorrhage,recombinant human TSG-6 or a siRNA targeting TSG-6 was injected into the cerebral *** TSG-6 administration downregulated the expression of NLRC4 and pyroptosis-associated proteins and alleviated brain edema and neurological ***,TSG-6 knockdown further increased the expression of NLRC4,which was accompanied by more severe astrocyte *** summary,our study revealed that TSG-6 provides neuroprotection against early brain injury after subarachnoid hemorrhage by suppressing NLRC4 inflammasome activation-induced astrocyte pyroptosis.

关键词： astrocyte early brain injury inflammasome NLRC4 pyroptosis subarachnoid hemorrhage tumor necrosis factor-stimulated gene-6(TSG-6)

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Gut microbial metabolite targets HDAC3-FOXK1-interferon axis in fibroblast-like synoviocytes to ameliorate rheumatoid arthritis

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Bone Research 2024年第2期12卷 421-437页

作者： Hongzhen Chen Xuekun Fu Xiaohao Wu Junyi Zhao Fang Qiu Zhenghong Wang Zhuqian Wang Xinxin Chen Duoli Xie Jie Huang Junyu Fan Xu Yang Yi Song Jie Li Dongyi He Guozhi Xiao Aiping Lu Chao Liang department of Systems Biology School of Life SciencesSouthern University of Science and TechnologyGuangdong Provincial Key Laboratory of Cell Microenvironment and Disease ResearchShenzhen Key Laboratory of Cell MicroenvironmentShenzhen 518055China Institute of Integrated Bioinfomedicine and Translational Science(IBTS) School of Chinese MedicineHong Kong Baptist UniversityHong Kong SAR 999077China department of Biochemistry School of MedicineSouthern University of Science and TechnologyGuangdong Provincial Key Laboratory of Cell Microenvironment and Disease ResearchShenzhen Key Laboratory of Cell MicroenvironmentShenzhen 518055China Division of Immunology and Rheumatology Stanford UniversityStanfordCA 94305USA VA Palo Alto Health Care System Palo AltoCA 94304USA Institute of Plant and Food Science Department of BiologySouthern University of Science and TechnologyShenzhen 518055China department of Rheumatology Guanghua Hospital Affiliated to Shanghai University of Traditional Chinese MedicineShanghai University of Traditional Chinese MedicineShanghaiChina department of Computational Biology St.Jude Children’s Research HospitalMemphisTNUSA department of laboratory Medicine Peking University Shenzhen HospitalShenzhenChina guangdong-Hong Kong-Macao Joint Lab on Chinese Medicine and Immune Disease Research Guangzhou 510006China Shanghai University of Traditional Chinese Medicine Shanghai 200032China State key laboratory of Proteomics National Center for Protein Sciences(Beijing)Beijing Institute of Lifeomics100850 BeijingChina

Rheumatoid arthritis(RA)is an autoimmune *** studies hold an opinion that gut microbiota is environmentally acquired and associated with RA ***,accumulating evidence demonstrates that genetics also shape the gut *** is known that some strains of inbred laboratory mice are highly susceptible to collagen-induced arthritis(CIA),while the others are resistant to ***,we show that transplantation of fecal microbiota of CIA-resistant C57BL/6J mice to CIA-susceptible DBA/1J mice confer CIA resistance in DBA/1J mice.C57BL/6J mice and healthy human individuals have enriched *** than DBA/1J mice and RA *** of *** prevents CIA in DBA/1J *** identify that *** mainly produces propionate and C57BL/6J mice and healthy human individuals have higher level of ***-like synoviocytes(FLSs)in RA are activated to undergo tumor-like *** disrupts HDAC3-FOXK1 interaction to increase acetylation of FOXK1,resulting in reduced FOXK1 stability,blocked interferon signaling and deactivation of *** treat CIA mice with propionate and show that propionate attenuates ***,a combination of propionate with anti-TNF etanercept synergistically relieves *** results suggest that *** or propionate could be an alternative or complementary approach to the current therapies.

关键词： HDAC3 cytes interferon

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Thiol-Disulfide Exchange Coordinates the Release of Nitric Oxide and Dexamethasone for Synergistic Regulation of Intestinal microenvironment in Colitis

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Research 2024年第2期6卷 285-300页

作者： Junna Lu Tongfei Shi Chengxin Shi Fangman Chen Chao Yang Xiaochun Xie Zheng Wang He Shen Jiaqi Xu Kam W.Leong Dan Shao School of Biomedical Sciences and Engineering South China University of TechnologyGuangzhou International CampusGuangzhouGuangdong 510006China National Engineering Research Center for Tissue Restoration and Reconstruction South China University of TechnologyGuangdong 510006China department of Plastic and Aesthetic Center The First Affliated Hospital of Zhejiang UniversityHangzhou 310000China department of Biomedical Engineering Columbia UniversityNew YorkNY 10027USA School of Medicine South China University of TechnologyGuangzhouGuangdong 510006China CAS key laboratory of nano-Bio Interface Suzhou Institute of Nano-Tech and NanoBionicsChinese Academy of SciencesSuzhou 215123China CAS key laboratory for Biomedical Efects of nanomaterials&nanosafety CAS Center for Excellence in NanoscienceNational Center for Nanoscience and TechnologyBeijing 100190China guangdong provincial key laboratory of Biomedical Engineering South China University of TechnologyGuangzhou 510006China key laboratory of Biomedical Materials and Engineering of the Ministry of education South China University of TechnologyGuangzhou 510006China

The cell-specific functions of nitric oxide(NO)in the intestinal microenvironment orchestrate its therapeutic effects in ulcerative *** most biomaterials show promise by eliciting the characteristics of NO,the insufficient storage,burst release,and pro-inflammatory side effects of NO remain as ***,we report the development of thiol-disulfide hybrid mesoporous organosilica nanoparticles(MONs)that improve the storage and sustained release of NO,broadening the therapeutic window of NO-based therapy against *** tailored NO-storing nanomaterials coordinated the release of NO and the immunoregulator dexamethasone(Dex)in the intestinal microenvironment,specifically integrating the alleviation of oxidative stress in enterocytes and the reversal of NO-exacerbated macrophage ***,such a synchronous operation was achieved by a self-motivated process wherein the thiyl radicals produced by NO release cleaved the disulfide bonds to degrade the matrix and release Dex via thiol-disulfide ***,the MON-mediated combination of NO and Dex greatly ameliorated intractable colitis compared with 5-aminosalicylic acid,even after delayed ***,our results reveal a key contribution of synergistic modulation of the intestinal microenvironment in NO-based colitis therapy and introduce thiol-disulfide hybrid nanotherapeutics for the management of inflammatory diseases and cancer.

关键词： sustained release disulfide

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Bimetallic nanoparticles as cascade sensitizing amplifiers for low-dose and robust cancer radio-immunotherapy

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Acta Pharmaceutica Sinica B 2024年第4期14卷 1787-1800页

作者： Yupeng Wang Lina Wang Tao Li Min Ouyang Hejian Xiong Dongfang Zhou department of Ultrasonic Diagnosis Zhujiang HospitalKey Laboratory of Mental Health of the Ministry of EducationNMPA Key Laboratory for Research and Evaluation of Drug Metabolism&Guangdong Provincial Key Laboratory of New Drug ScreeningSchool of Pharmaceutical SciencesSouthern Medical UniversityGuangzhou 510515China Testing and Analysis Center Hebei Normal UniversityShijiazhuang 050024China department of Mechanical Engineering The University of Texas at DallasRichardsonTX 75080USA

Radiotherapy(RT)is one of the most feasible and routinely used therapeutic modalities for treating malignant *** particular,immune responses triggered by RT,known as radio-immunotherapy,can partially inhibit the growth of distantly spreading tumors and recurrent ***-ever,the safety and efficacy of radio-immunotherapy is impeded by the radio-resistance and poor immu-nogenicity of ***,we report oxaliplatin(IV)-iron bimetallic nanoparticles(OXA/Fe NPs)as cascade sensitizing amplifiers for low-dose and robust *** OXA/Fe NPs exhibit tumor-specific accumulation and activation of OXA(I)and Fe^(2+)in response to the reductive and acidic microenvironment within tumor *** cascade reactions of the released metallic drugs can sensitize RT by inducing DNA damage,increasing ROS and O_(2) levels,and amplifying the immunogenic cell death(ICD)effect after RT to facilitate potent immune *** a result,OXA/Fe NPs-based low-dose RT triggered a robust immune response and inhibited the distant and metastatic tumors effectively by a strong abscopal ***,a long-term immunological memory effect to protect mice from tumor rechal-lenging is ***,the bimetallic NPs-based cascade sensitizing amplifier system offers an effi-cient radio-immunotherapy regimen that addresses the key challenges.

关键词： Bimetallic nanoparticles Radio-immunotherapy Cascade sensitizing amplifier,Oxaliplatin Fenton-typeHaber-Weiss reaction Radiosensitization Immunogenic cell death Radio-resistance

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nanomedicine-mediated immunogenic cell death and its combination with immune checkpoint blockade therapy

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Science China Technological Sciences 2024年第8期67卷 2350-2362页

作者： CHEN JunBin ZHANG YuXi SU Miao ZHU YueQiang YANG XianZhu School of Biomedical Sciences and Engineering South China University of TechnologyGuangzhou International Campus National Engineering Research Center for Tissue Restoration and Reconstruction Guangdong Provincial Key Laboratory of Biomedical Engineering key laboratory of Biomedical Materials and Engineering of the Ministry of education South China University of Technology

Cancer immunotherapies, which train the natural immune system to specifically kill tumor cells while sparing the healthy cells,have helped revolutionize cancer treatments and demonstrated promising clinical therapeutic benefits for decades. However, the therapeutic outcome of immunotherapies, even for the most successful immune checkpoint blockade(ICB) therapy, remains unsatisfactory in the clinical practice, mainly due to the low immunogenicity of solid tumors and its immunosuppressive tumor microenvironment(TME). Notably, several cancer treatment modalities, including chemotherapy, radiotherapy, and phototherapy, have been revealed to evoke tumor immunogenicity and reverse immunosuppressive TME via inducing immunogenic cell death(ICD) of tumor cells, which synergistically sensitized tumors to ICB therapy. nanomedicines have been extensively applied to augment ICD-inducing treatment modalities and potentiate ICB therapeutic efficacy therapy due to the opportune convergence of immunotherapy and nanotechnology. Here, we discuss the recent advances in nanomedicine-mediated ICD and its combination with ICB therapy.

关键词： cancer immunotherapy nanomedicine immunogenic cell death immune checkpoint blockade

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Artificial intelligence-based analysis of tumor-infiltrating lymphocyte spatial distribution for colorectal cancer prognosis

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Chinese Medical Journal 2024年第4期137卷 421-430页

作者： Ming Cai Ke Zhao Lin Wu Yanqi Huang Minning Zhao Qingru Hu Qicong Chen Su Yao Zhenhui Li Xinjuan Fan Zaiyi Liu department of Radiology Guangdong Provincial People’s Hospital(Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhouGuangdong 510080China guangdong provincial key laboratory of Artificial Intelligence in Medical Image Analysis and Application GuangzhouGuangdong 510080China guangdong Cardiovascular Institute Guangdong Provincial People’s Hospital(Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhouGuangdong 510080China Medical Research Institute Guangdong Provincial People’s Hospital(Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhouGuangdong 510080China department of Pathology The Third Affiliated Hospital of Kunming Medical UniversityYunnan Cancer HospitalYunnan Cancer CenterKunmingYunnan 650118China The Second School of Clinical Medicine Southern Medical UniversityGuangzhouGuangdong 510515China Institute of Computing Science and Technology Guangzhou UniversityGuangzhouGuangdong 510006China department of Pathology Guangdong Provincial People’s Hospital(Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhouGuangdong 510080China department of Pathology The Sixth Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdong 510655China

Background:Artificial intelligence(AI)technology represented by deep learning has made remarkable achievements in digital pathology,enhancing the accuracy and reliability of diagnosis and prognosis *** spatial distribution of CD3^(+)and CD8^(+)T cells within the tumor microenvironment has been demonstrated to have a significant impact on the prognosis of colorectal cancer(CRC).This study aimed to investigate CD3_(CT)(CD3^(+)T cells density in the core of the tumor[CT])prognostic ability in patients with CRC by using AI ***:The study involved the enrollment of 492 patients from two distinct medical centers,with 358 patients assigned to the training cohort and an additional 134 patients allocated to the validation *** facilitate tissue segmentation and T-cells quantification in whole-slide images(WSIs),a fully automated workflow based on deep learning was *** the completion of tissue segmentation and subsequent cell segmentation,a comprehensive analysis was ***:The evaluation of various positive T cell densities revealed comparable discriminatory ability between CD3_(CT) and CD3-CD8(the combination of CD3^(+)and CD8^(+)T cells density within the CT and invasive margin)in predicting mortality(C-index in training cohort:0.65 vs.0.64;validation cohort:0.69 vs.0.69).The CD3_(CT) was confirmed as an independent prognostic factor,with high CD3_(CT) density associated with increased overall survival(OS)in the training cohort(hazard ratio[HR]=0.22,95%confidence interval[CI]:0.12–0.38,P<0.001)and validation cohort(HR=0.21,95%CI:0.05–0.92,P=0.037).Conclusions:We quantify the spatial distribution of CD3^(+)and CD8^(+)T cells within tissue regions in WSIs using AI *** CD3_(CT) confirmed as a stage-independent predictor for OS in CRC ***,CD3_(CT) shows promise in simplifying the CD3-CD8 system and facilitating its practical application in clinical settings.

关键词： Colorectal cancer Artificial intelligence Deep learning Digital pathology Prognosis Immune cells CD3 CD8 TME

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Hepatic Zbtb18 (Zinc Finger and BTB Domain Containing 18) alleviates hepatic steatohepatitis via FXR (Farnesoid X Receptor)

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Signal Transduction and Targeted Therapy 2024年第2期9卷 766-781页

作者： Lei Zhang Jiabing Chen Xiaoying Yang Chuangpeng Shen Jiawen Huang Dong Zhang Naihua Liu Chaonan Liu Yadi Zhong Yingjian Chen Kaijia Tang Jingyi Guo Tianqi Cui Siwei Duan Jiayu Li Shangyi Huang Huafeng Pan Huabing Zhang Xiaoqiang Tang Yongsheng Chang Yong Gao State key laboratory of Traditional Chinese Medicine Syndrome Science and Technology Innovation CenterGuangzhou University of Chinese MedicineGuangzhouChina key laboratory of Immune microenvironment and Disease(Ministry of education) Tianjin Key Laboratory of Cellular Homeostasis and DiseaseDepartment of Physiology and PathophysiologyTianjin Medical UniversityTianjinChina Jiangsu key laboratory of Immunity and Metabolism Department of Pathogen Biology and ImmunologyJiangsu International Laboratory of Immunity and MetabolismXuzhou Medical UniversityXuzhouChina department of Endocrinology The First Clinical CollegeGuangzhou University of Chinese MedicineGuangdongChina The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine ShenzhenChina Jiangsu Collaborative Innovation Center of Traditional Chinese Medicine in Prevention and Treatment of tumor Nanjing University of Chinese MedicineNanjingChina department of Biochemistry and Molecular Biology Metabolic Disease Research CenterSchool of Basic MedicineAnhui Medical UniversityHefeiChina key laboratory of Birth Defects and Related Diseases of Women and Children of MOE State Key Laboratory of BiotherapyWest China Second University HospitalSichuan UniversityChengduChina

A lasting imbalance between fatty acid synthesis and consumption leads to non-alcoholic fatty liver disease(NAFLD),coupled with hepatitis and insulin *** the details of the underlying mechanisms are not fully ***,we unraveled that the expression of the transcription factor Zbtb18 is markedly decreased in the livers of both patients and murine models of *** Zbtb18 knockout promoted NAFLD features like impaired energy expenditure and fatty acid oxidation(FAO),and induced insulin ***,hepatic Zbtb18 overexpression alleviated hepato-steatosis,insulin resistance,and hyperglycemia in mice fed on a high-fat diet(HFD)or in diabetic ***,in vitro and in vivo mechanistic studies revealed that Zbtb18 transcriptional activation of Farnesoid X receptor(FXR)mediated FAO and Clathrin Heavy Chain(CLTC)protein hinders NLRP3 inflammasome *** key mechanism by which hepatocyte’s Zbtb18 expression alleviates NAFLD and consequent liver fibrosis was further verified by FXR’s deletion and forced expression in mice and cultured mouse primary hepatocytes(MPHs).Moreover,CLTC deletion significantly abrogated the hepatic Zbtb18 overexpression-driven inhibition of NLRP3 inflammasome activity in ***,Zbtb18 transcriptionally activates the FXR-mediated FAO and CLTC expression,which inhibits NLRP3 inflammasome’s activity alleviating inflammatory stress and insulin resistance,representing an attractive remedy for hepatic steatosis and fibrosis.

关键词： hepatic Hepatic impaired

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A novel engineered IL-21 receptor arms T-cell receptor-engineered T cells(TCR-T cells)against hepatocellular carcinoma

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Signal Transduction and Targeted Therapy 2024年第5期9卷 2215-2230页

作者： Wei Zhu Zhiming Zhang Jinzhang Chen Xiaolan Chen Lei Huang Xiaoyong Zhang Xuan Huang Na Ma Weikang Xu Xuan Yi Xinyu Lu Xin Fu Siwei Li Guoheng Mo Yiyue Wang Guosheng Yuan Mengya Zang Qi Li Xiaotao Jiang Yajing He Sha Wu Yukai He Yongyin Li Jinlin Hou State key laboratory of Organ Failure Research Guangdong Provincial Key Laboratory of Viral Hepatitis ResearchDepartment of Infectious DiseasesNanfang HospitalSouthern Medical UniversityGuangzhouChina Institute of Cellular Medicine Newcastle University Medical SchoolNewcastleUK department of Pathology The First People’s Hospital of FoshanFoshanChina Dermatology Hospital Southern Medical UniversityGuangzhouChina department of Immunology School of Basic Medical SciencesSouthern Medical UniversityGuangzhouChina Microbiome Medicine Center Department of Laboratory MedicineZhujiang HospitalSouthern Medical UniversityGuangzhouChina key laboratory of Proteomics of guangdong Province Demonstration Center for Experimental Education of Basic Medical Sciences of ChinaGuangzhouChina Medical College of Georgia Augusta University112015th StreetAugustaGAUSA

Strategies to improve T cell therapy efficacy in solid tumors such as hepatocellular carcinoma(HCC)are urgently *** common cytokine receptorγchain(γc)family cytokines such as IL-2,IL-7,IL-15 and IL-21 play fundamental roles in T cell development,differentiation and effector *** study aims to determine the combination effects of IL-21 in T cell therapy against HCC and investigate optimized strategies to utilize the effect of IL-21 signal in T cell *** antitumor function of AFP-specific T cell receptor-engineered T cells(TCR-T)was augmented by exogenous IL-21 in vitro and in ***-21 enhanced proliferation capacity,promoted memory differentiation,downregulated PD-1 expression and alleviated apoptosis in TCR-T after activation.A novel engineered IL-21 receptor was established,and TCR-T armed with the novel engineered IL-21 receptors(IL-21R-TCR-T)showed upregulated phosphorylated STAT3 expression without exogenous IL-21 ***-21R-TCR-T showed better proliferation upon activation and superior antitumor function in vitro and in ***-21R-TCR-T exhibited a less differentiated,exhausted and apoptotic phenotype than conventional TCR-T upon repetitive tumor antigen *** novel IL-21 receptor in our study programs powerful TCR-T and can avoid side effects induced by IL-21 systemic *** novel IL-21 receptor creates new opportunities for next-generation TCR-T against HCC.

关键词： hepatocellular TCR utilize

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Small-molecule agents for cancer immunotherapy

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Acta Pharmaceutica Sinica B 2024年第3期14卷 905-952页

作者： Fang Wang Kai Fu Yujue Wang Can Pan Xueping Wang Zeyu Liu Chuan Yang Ying Zheng Xiaopeng Li Yu Lu Kenneth Kin Wah To Chenglai Xia Jianye Zhang Zhi Shi Zeping Hu Min Huang Liwu Fu State key laboratory of Oncology in South China Collaborative Innovation Center for Cancer MedicineGuangdong Esophageal Cancer InstituteGuangdong Provincial Clinical Research Center for CancerSun Yat-sen University Cancer CenterGuangzhou 510060China School of Pharmaceutical Sciences Tsinghua-Peking Center for Life SciencesBeijing Frontier Research Center for Biological StructureTsinghua UniversityBeijing 100084China State key laboratory of Drug Research Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China department of Cell Biology&Institute of Biomedicine National Engineering Research Center of Genetic MedicineMOE Key Laboratory of Tumor Molecular BiologyGuangdong Provincial Key Laboratory of Bioengineering MedicineCollege of Life Science and TechnologyJinan UniversityGuangzhou 510632China Guangzhou Municipal and guangdong provincial key laboratory of Molecular Target&Clinical Pharmacology NMPA and State Key Laboratory of Respiratory DiseaseSchool of Pharmaceutical Sciences and the Fifth Affiliated HospitalGuangzhou Medical UniversityGuangzhou 511436China School of Pharmacy The Chinese University of Hong KongHong Kong 999077China Affiliated Foshan Maternity and Child Healthcare Hospital Southern Medical UniversityFoshan 528000China

Cancer immunotherapy,exemplified by the remarkable clinical benefits of the immune checkpoint blockade and chimeric antigen receptor T-cell therapy,is revolutionizing cancer *** induce long-term tumor regression and overall survival benefit in many types of *** the advances in our knowledge about the tumor immune microenvironment,remarkable progress has been made in the development of small-molecule drugs for *** molecules targeting PRR-associated pathways,immune checkpoints,oncogenic signaling,metabolic pathways,cytokine/chemokine signaling,and immune-related kinases have been extensively *** of smallmolecule immunotherapeutic drugs and their combinations with other antitumor modalities are under active clinical investigations to overcome immune tolerance and circumvent immune checkpoint inhibitor ***,we review the latest development of small-molecule agents for cancer immunotherapy by targeting defined pathways and highlighting their progress in recent clinical investigations.

关键词： Cancer immunotherapy Small-molecule agents Immune checkpoints Oncogenic signaling Metabolic pathways Cytokine/chemokine signaling Antitumor immunity tumor immune microenvironment

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Two-color emissive AIEgens with anti-Kasha property for dual-organelle imaging and phototherapy

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Science China Chemistry 2024年第5期67卷 1740-1752页

作者： Pu Chen Guogang Shan Qingli Nie Yuting Yan Pengfei Zhang Zujin Zhao Hai-Tao Feng Ben Zhong Tang AIE Research Center Shaanxi Key Laboratory of PhytochemistryCollege of Chemistry and Chemical EngineeringBaoji University of Arts and SciencesBaoji 721013China Institute of Functional Material Chemistry and National&Local United Engineering Lab for Power Battery Faculty of ChemistryNortheast Normal UniversityChangchun 130024China College of Chemistry&Materials Science Northwest UniversityXi’an 710127China guangdong key laboratory of nanomedicine CAS-HK Joint Lab of BiomaterialsCAS Key Laboratory of Biomedical Imaging Science and SystemShenzhen Engineering Laboratory of Nanomedicine and NanoformulationsCAS Key Lab for Health InformaticsShenzhen Institutes of Advanced TechnologyChinese Academy of SciencesShenzhen 518055China State key laboratory of Luminescent Materials and Devices Key Laboratory of Luminescence from Molecular Aggregates of Guangdong ProvinceSouth China University of TechnologyGuangzhou 510640China School of Science and Engineering Shenzhen Institute of Aggregate Science and TechnologyThe Chinese University of Hong KongShenzhen(CUHK-Shenzhen)Shenzhen 518172China

Despite the rapid development of probes for targeting single organelle, the construction of robust dual-organelle targeting probes with multicolor emission was rarely reported. Herein, two dual-emissive aggregation-induced emission luminogens(AIEgens)with donor-π-acceptor structures were designed and synthesized, namely QT-1 and QF-2. Both two AIEgens exhibited excitation wavelength-dependence defying the Kasha's rule, and could stain lipid droplets(LDs) and mitochondria in blue and red fluorescence, respectively. Moreover, thanks to the near-infrared emission and abundant reactive oxygen species(ROS) generation efficiency of QT-1, it was chosen as a photodynamic therapy agent to selectively kill cancer cells from normal cells. Upon light irradiation, an obvious decrease of mitochondrial membrane potential(MMP) and serious change of mitochondrial shape in cells were observed, which corresponded to the efficient inhibition of tumor growth in vivo. This work afforded a promising strategy for the construction of multicolor emission by tuning anti-Kasha behaviors and expanding their application in dualorganelle targeting-based phototheranostics.

关键词： aggregation-induced emission anti-Kasha luminescence fluorescent probe bioimaging photodynamic therapy

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