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Silicon-based metal-organic frameworks(SiMOFs)for immunogenic cell death in cancer therapy

Nano Research 2025年第1期18卷 628-641页

作者： Min Han Zishan Chen Shiying Zhou Zunde Liao Xiangting Yi Yao He Yiling Zhong Kam W.Leong College of Pharmacy State Key Laboratory of Bioactive Molecules and Druggability AssessmentJinan UniversityGuangzhou 511443China Department of Biomedical Engineering Columbia UniversityNew YorkNY 10027USA Institute of Functional Nano and Soft Materials(FUNSOM) Soochow UniversitySuzhou 215123China

Silicon-based nanomaterials,known for their unique properties and favorable biocompatibility,significantly impact sectors like energy,electronics,and ***,metalorganic frameworks(MOFs)have emerged as promising candidates for biomedicine,characterized by adjustable chemical composition,high porosity,and ***,the combination of silicon with MOFs to create silicon-based MOF nanostructures(SiMOFs)remains ***,we establish a diverse library of SiMOFs with various nanostructures,including flower-like,capsule-like,hexagonal snowflake-like,and necklace-like morphologies via microwave-assisted *** SiMOFs,with their spacious interiors,are ideal for drug *** are used to load drugs and create drug-loaded SiMOFs(e.g.,SiFeO).SiFeO exhibits excellent photothermal effects and high reactive oxygen species(ROS)generation capacity,enabling synergistic treatments involving chemochemodynamic-photothermal *** approach efficiently triggers immunogenic cell death(ICD)and demonstrates excellent antitumor efficacy in *** staining reveals that the synergistic therapy can modulate the tumor microenvironment(TME)by reducing M2-phenotype macrophages,increasing the activation of antigen-presenting cells(APCs),enhancing the infiltration of CD4^(+)and CD8^(+)T cells,elevating Granzyme B production,and decreasing the presence of immunosuppressive regulatory T cells(Tregs).Consequently,drug-loaded SiMOFs-mediated combination therapy effectively reverses the immunosuppressive TME and activates robust antitumor immune responses by inducing ICD in tumor cells,ultimately achieving superior anticancer efficacy.

关键词： silicon-based nanomaterials nanocarriers immunogenic cell death antitumor immune responses

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immunogenic cell death effects induced by doxorubicin improved chemo-immunotherapy via restoration of granzyme B activity

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Nano Research 2023年第12期16卷 13250-13258页

作者： Tao Huang Xiaofan Sun Yingqiu Qi Xi Yang Linyao Fan Mengdie Chen Yale Yue Hong Ge Yiye Li Guangjun Nie Huan Min Xianfu Sun Department of Breast Disease The Affiliated Cancer Hospital of Zhengzhou University&Henan Cancer HospitalHenan Institute of Advanced TechnologyZhengzhou UniversityZhengzhou 450008China Department of Pharmacology School of Basic Medical SciencesZhengzhou UniversityZhengzhou 450001China Department of Radiation Oncology The Affiliated Cancer Hospital of Zhengzhou University&Henan Cancer HospitalZhengzhou 450003China CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety&CAS Center for Excellence in Nanoscience National Center for Nanoscience and TechnologyBeijing 100190China

Chemotherapy remains one of the irreplaceable treatments for cancer *** use of immunogenic cell death(ICD)-inducing chemotherapeutic drugs offers a practical strategy for killing cancer cells,simultaneously eliciting an antitumor immune response by promoting the recruitment of cytotoxic immune cells and production of granzyme B(GrB).However,numerous malignant cancers adaptively acquired the capacity of secreting serpinb9(Sb9),a physiological inhibitor of GrB,which can reversibly inhibit the biological activity of *** circumvent this dilemma,in this study,an integrated tailor-made nanomedicine composed of tumor-targeting peptide(Arg-Gly-Asp,RGD)decorated liposome,doxorubicin(DOX,an effective ICD inducer),and the compound 3034(an inhibitor of Sb9),is developed(termed as D3RL)for breast cancer *** vitro and in vivo studies show that D3RL can directly kill tumor cells and trigger the host immune response by inducing ***,D3RL can competitively relieve the inhibition of Sb9 to *** restored GrB can not only effectively induce tumor immunotherapy,but also degrade matrix components in the tumor microenvironment,consequently improving the infiltration of immune cells and the penetration of nanomedicines,which in return enhance the combined antitumor *** together,this work develops an integrated therapeutic solution for targeted production and restoration of GrB to achieve a combined chemo-immunotherapy for breast cancer.

关键词： immunogenic cell death granzyme B serpinb9 chemo-immunotherapy nanomedicine

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immunogenic cell death-related long noncoding RNA influences immunotherapy against lung adenocarcinoma

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Oncology Research 2023年第5期31卷 753-767页

作者： DONGJIE SUN CHI ZHANG Department of Translational Medicine The First Hospital of Jilin UniversityChangchunChina College of Basic Medical Sciences Jilin UniversityChangchunChina Department of Anesthesiology The First Hospital of Jilin UniversityChangchunChina

Lung adenocarcinoma(LUAD)is the leading cause of cancer-related deaths,accounting for over a million deaths worldwide *** cell death(ICD)elicits an adaptive immune ***,the role of ICD-related long noncoding RNAs(lncRNAs)in LUAD is *** this study,we investigated the characteristics of the tumor microenvironment in LUAD,the prognostic significance of ICD-related lncRNAs,and the half-maximal inhibitory concentration(IC50)of possible chemotherapeutic *** sorted prognostic lncRNAs using univariate Cox regression and constructed a risk signature based on *** then confirmed the model’s accuracy and generated a ***,we performed immune microenvironment analysis,somatic mutation calculation,Tumor Immune Dysfunction and Exclusion(TIDE)analysis,and anticancer pharmaceutical IC50 *** absolute shrinkage and selection operator Cox regression identified 27 prognostic lncRNAs related to ICD,and a unique risk signature using 10 ICD-related lncRNAs was *** risk score was confirmed to be a reliable predictor of survival,with the highest c-index *** signature had a remarkable predictive performance with clinical applicability and could accurately predict the overall survival in ***,the lncRNA signature was closely associated with immunocyte *** also analyzed the correlation between the risk score,tumor-infiltrating immune cells,and prognosis and identified high immune and ESTIMATE scores in low-risk ***,we observed elevated checkpoint gene expression and low TIDE scores in high-risk patients,indicating a good immunotherapy ***,high-risk patients were shown to be susceptible to anticancer ***,our unique risk signature comprising 10 ICD-related lncRNAs was demonstrated to indicate the characteristics of the tumor-immune microenvironment in LUAD,predict patients’overall survival,and guide individualized treatment.

关键词： Lung adenocarcinoma immunogenic cell death Prognostic model Bioinformatics Tumor infiltration

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Endoplasmic reticulum targeted AIE bioprobe as a highly efficient inducer of immunogenic cell death

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Science China Chemistry 2020年第10期63卷 1428-1434页

作者： Jun Li Heqi Gao Ruihua Liu Chao Chen Sheng Zeng Qian Liu Dan Ding Key Laboratory of Bioactive Materials Ministry of Education College of Life Sciencesand State Key Laboratory of Medicinal Chemical BiologyNankai UniversityTianjin 300071China Department of Urology Tianjin First Central HospitalTianjin 300192China

Focused oxidative stress of the specific organelles(e.g.,endoplasmic reticulum(ER)and mitochondrion)of cancer cells can boost the immunogenic cell death(ICD)effect for cancer ***,an ER-targeted bioprobe with aggregationinduced emission(AIE)characteristics(TPE-PR-FFKDEL)was rationally designed and synthesized by integrating a new AIE photosensitizer with ER targeting peptide,which has been demonstrated to be able to efficiently induce ER oxidative stress to evoke *** with the photosensitizer hypericin that is well-known as an ER-targeted ICD inducer,TPE-PR-FFKDEL can lead to more robust emission of immunostimulatory damage-associated molecular patterns such as surface-exposed calreticulin,ATP secretion,and high-mobility group protein B1(HMGB1)and heat shock protein 70(HSP 70)***,a range of immune responses are activated to protect mice from the attack of cancer cells in vivo.

关键词： immunogenic cell death endoplasmic reticulum oxidative stress aggregation-induced emission reactive oxygen species

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Mitochondria-targeted nano-AIEgens as a powerful inducer for evoking immunogenic cell death

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Chinese Chemical Letters 2024年第5期35卷 338-343页

作者： Kun-Heng Li Hong-Yang Zhao Dan-Dan Wang Ming-Hui Qi Zi-Jian Xu Jia-Mi Li Zhi-Li Zhang Shi-Wen Huang Key Laboratory of Biomedical Polymers of Ministry of Education Department of ChemistryWuhan UniversityWuhan 430072China

AIEgens can serve as an effective platform for the construction of photosensitizer-based immunogenic cell death(ICD)*** date,several mitochondria or endoplasmic reticulum(ER)-targeted aggregationinduced emission(AIE)molecules have been developed and have evoked massive ICD in ***,due to the complex physicochemical environment in cells,these small AIE molecules cannot maintain a stable aggregate state,which not only affects the fluorescence intensity of the photosensitizer but also decreases the generation of reactive oxygen species(ROS),and thus reducing the effect of the photosensitizer to elicit ***-based nanomicelles,which maintain a stable micellar structure,can prevent defects of AIE molecules in photodynamic therapy(PDT)***,in this study,a mitochondria-targeted AIE nanophotosensitizer was synthesized and used as a highly potent ICD inducer for vaccine preparation and tumor prevention.

关键词： Aggregation induced emission Photodynamic therapy immunogenic cell death Reactive oxygen species Nanophotosensitizer Mitochondria

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Evoking robust immunogenic cell death by synergistic sonodynamic therapy and glucose depletion using Au clusters/single atoms modified TiO_(2)nanosheets

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Nano Research 2023年第7期16卷 9730-9742页

作者： Xiuxin Lu Kun Qiao Firdoz Shaik Yang Zheng Zhaoyou Chu Haisheng Qian Xijun Liu Weiqing Zhang Department of Research Guangxi Medical University Cancer HospitalNanning 530021China Department of Breast Surgery Harbin Medical University Cancer HospitalHarbin 150081China Department of Biotechnology Vignan’s Foundation for ScienceTechnology&ResearchGuntur 522213India Department of Breast Surgery Guangxi Medical University Cancer HospitalNanning 530021China School of Biomedical Engineering Research and Engineering Center of Biomedical MaterialsAnhui Provincial Institute of Translational MedicineAnhui Medical UniversityHefei 230032China State Key Laboratory of Featured Metal Materials and Life-cycle Safety for Composite Structures School of ResourceEnvironments and MaterialsGuangxi UniversityNanning 530004China

Facilitated by reactive oxygen species(ROS)-involved therapies,tumor cells undergo immunogenic cell death(ICD)to stimulate long-term immunity ***,it is hard to trigger abundant and large-scale ICD for satisfactory cancer ***,a multifunctional sonosensitizer that consists of Au single atoms and clusters anchored on TiO_(2)nanosheets(named Au_(S/C)-TiO_(2))is reported for augmented sonodynamic therapy(SDT)and glucose depletion,which ultimately induce robust ICD due to the improved ROS generation and strong endoplasmic reticulum(ER)*** synergy effect between Au cluster/single atom with TiO_(2)nanosheets intensifies apoptosis and ICD pathways to inhibit 80%of tumor cells through in vivo ***,immune cells in vivo analyses verify the effectiveness of Au_(S/C)-TiO_(2)sonosensitizer towards the induction of antitumor *** study thus reveals that simultaneous presence of ROS generation and strong ER stress can efficiently evoke a strong ICD-mediated immune response.

关键词： single atom cluster titania sonodynamic therapy immunogenic cell death multifunctional

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NIR-Ⅱ responsive Janus nanoparticles amplify immunogenic cell death for enhanced cancer immunotherapy

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Science China(Technological Sciences) 2024年第1期67卷 321-329页

作者： CHEN BeiBei GUO KangLi WANG HaoRan XU Fu-Jian WANG JuLin ZHAO NaNa State Key Laboratory of Chemical Resource Engineering Beijing University of Chemical TechnologyBeijing 100029China Key Laboratory of Biomedical Materials of Natural Macromolecules(Beijing University of Chemical Technology) Beijing Laboratory of Biomedical MaterialsBeijing University of Chemical TechnologyBeijing 100029China College of Materials Sciences and Engineering Beijing University of Chemical TechnologyBeijing 100029China Beijing Key Laboratory of Electrochemical Process and Technology for Materials Beijing University of Chemical TechnologyBeijing 100029China

Immunotherapy brings new hope for tumor treatment by inducing immunogenic cell death(ICD)of tumor ***,insufficient immunogenicity and low immune response rate greatly limit antitumor ***,by optimizing the composition and morphology,the rational design of Janus nanoparticles composed of Fe_(3)O_(4) nanospheres and SiO_(2)nanorods was realized for enhanced cancer immunotherapy through amplified *** glucose oxidase(GOx)was loaded by the Janus nanoparticles,the resultant M-FS-GOx consumes glucose at tumor sites to generate gluconic acid and hydrogen peroxide(H_(2)O_(2))for starvation therapy while the H_(2)O_(2)supply promotes the production of highly toxic·OH to achieve effective chemodynamic therapy(CDT).Under a 1064 nm light irradiation,the photothermal effect of M-FS-GOx enhances the enzyme activity of GOx for improved starvation ***,both tumor-associated antigens released during the process of ICD and the intrinsic immunoadjuvant property of M-FS-GOx stimulate dendritic cell maturation to activate antitumor immune *** work provides a promising strategy for the construction of Janus nanoparticles to achieve enhanced cancer immunotherapy through combination therapy-amplified ICD.

关键词： Janus nanoparticles immunogenic cell death cancer immunotherapy

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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 CampusGuangzhou 511442China National Engineering Research Center for Tissue Restoration and Reconstruction Guangdong Provincial Key Laboratory of Biomedical EngineeringKey Laboratory of Biomedical Materials and Engineering of the Ministry of EducationSouth China University of TechnologyGuangzhou 510006China

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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Endoplasmic reticulum-targeted delivery of celastrol and PD-L1 siRNA for reinforcing immunogenic cell death and potentiating cancer immunotherapy

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Acta Pharmaceutica Sinica B 2024年第8期14卷 3643-3660页

作者： Jie Wang Zilong Zhang Yan Zhuo Zhuan Zhang Rongrong Chen Li Liang Xiaohe Jiang Di Nie Chang Liu Zhiwen Zou Xiang Li Jiaxin Li Bingqi Wang Rui Wang Yong Gan Miaorong Yu School of Pharmacy Shanghai University of Traditional Chinese MedicineShanghai 201203China State Key Laboratory of Drug Research Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China Jiangxi Medical College Nanchang UniversityNanchang 330006China School of Pharmacy Nanjing University of Chinese MedicineNanjing 210023China University of Chinese Academy of Sciences Beijing 100049China NMPA Key Laboratory for Quality Research and Evaluation of Pharmaceutical Excipients National Institutes for Food and Drug ControlBeijing 100050China

The prospect of employing chemoimmunotherapy targeted towards the endoplasmic reticulum(ER)presents an opportunity to amplify the synergistic effects of chemotherapy and *** this study,we initially validated celastrol(CEL)as an inducer of immunogenic cell death(ICD)by promoting ER stress and autophagy in colorectal cancer(CRC)***,an ER-targeted strategy was posited,involving the codelivery of CEL with PD-L1 small interfering RNAs(siRNA)using KDEL peptide-modified exosomes derived from milk(KME),to enhance chemoimmunotherapy *** findings demonstrate the efficient transportation of KME to the ER via the Golgi-to-ER *** to their non-targeting counterparts,KME exhibited a significant augmentation of the CEL-induced ICD ***,it facilitated the release of danger signaling molecules(DAMPs),thereby stimulating the antigen-presenting function of dendritic cells and promoting the infiltration of T cells into the ***,the ER-targeted delivery of PD-L1 siRNA resulted in the downregulation of both intracellular and membrane PD-L1 protein expression,consequently fostering the proliferation and activity of CD8^(+)T ***,the ER-targeted formulation exhibited enhanced anti-tumor efficacy and provoked anti-tumor immune responses against orthotopic colorectal tumors in ***,a robust ER-targeted delivery strategy provides an encouraging approach for achieving potent cancer chemoimmunotherapy.

关键词： Chemoimmunotherapy Targeted drug delivery Endoplasmic reticulum Endoplasmic reticulum stress immunogenic cell death siRNA Chemoimmunotherapy Targeted drug delivery Endoplasmic reticulum Endoplasmic reticulum stress immunogenic cell death siRNA

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Perfluorooctyl bromide nanoemulsions holding MnO_(2) nanoparticles with dual-modality imaging and glutathione depletion enhanced HIFU-eliciting tumor immunogenic cell death

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Acta Pharmaceutica Sinica B 2022年第2期12卷 967-981页

作者： Xinping Kuai Yuefei Zhu Zheng Yuan Shengyu Wang Lin Lin Xiaodan Ye Yiping Lu Yu Luo Zhiqing Pang Daoying Geng Bo Yin Department of Radiology Huashan HospitalFudan UniversityShanghai 200040China School of Pharmacy Fudan UniversityKey Laboratory of Smart Drug DeliveryMinistry of EducationShanghai 201203China Department of Radiology Shanghai First Maternity and Infant HospitalTongji University School of MedicineShanghai 201204China Department of Radiology Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghai 201800China Department of Radiology Shanghai Chest HospitalShanghai Jiao Tong UniversityShanghai 200030China State Key Laboratory of High Performance Ceramics and Superfine Microstructure School of Chemical Science and EngineeringShanghai 200092China

Tumor-targeted immunotherapy is a remarkable breakthrough,offering the inimitable advantage of specific tumoricidal effects with reduced immune-associated ***,existing platforms suffer from low efficacy,inability to induce strong immunogenic cell death(ICD),and restrained capacity of transforming immune-deserted tumors into immune-cultivated ***,an innovative platform,perfluorooctyl bromide(PFOB)nanoemulsions holding MnO_(2) nanoparticles(MBP),was developed to orchestrate cancer immunotherapy,serving as a theranostic nanoagent for MRI/CT dual-modality imaging and advanced *** simultaneously depleting the GSH and eliciting the ICD effect via highintensity focused ultrasound(HIFU)therapy,the MBP nanomedicine can regulate the tumor immune microenvironment by inducing maturation of dendritic cells(DCs)and facilitating the activation of CD8^(+)and CD4^(+)T *** synergistic GSH depletion and HIFU ablation also amplify the inhibition of tumor growth and lung ***,these findings inaugurate a new strategy of tumor-targeted immunotherapy,realizing a novel therapeutics paradigm with great clinical significance.

关键词： immunogenic cell death Nanoemulsions Manganese dioxide nanoparticles Glutathione depletion Dual-modality imaging High-intensity focused ultrasound Tumor microenvironment

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