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Hybrid transcytosis nanopomegranates for sensitizing breast cancer radiotherapy in deep tumor tissue

nano Research 2023年第5期16卷 7260-7268页

作者： Li Wang Liang Xiao Zhengyang Zhao Kai Zhong Weiliang Zhu Hao Liu Xiaoqiu Li department of Oncology Zhujiang HospitalSouthern Medical UniversityGuangzhou 510282China guangdong provincial key laboratory of tumor Interventional Diagnosis and Treatment Zhuhai People's Hospital(Zhuhai Hospital Affiliated with Jinan University)Zhuhai 519000China department of Radiation Oncology Affiliated Cancer Hospital&Institute of Guangzhou Medical UniversityGuangzhou 510095China department of Radiation Oncology The First Affiliated Hospital of Anhui Medical UniversityHefei 230022China

As a standard cancer treatment method,radiotherapy(RT)has cured or alleviated over half cancer bearing patients worldwide more than 100 ***,the therapeutic outcome is seriously hindered by the resistant tumor microenvironment(TME).Hypoxia is a critical factor of vicious TME that causes radiation resistance owing to the insufficiency of oxygen for DNA damage ***,severe vascular dysfunction and pyknomorphic extracellular matrix(ECM)in deep tumor tissues substantially limit radiosensitizer penetration and oxygen diffusion from vessels into tightly packed tumor *** this study,we develop a hybrid transcytosis nanopomegranate(HTP)with high transcytosis potential in response to TME *** is architected by self-assembly of small CuS and Au nanoparticles(NPs)at normal physiological *** can rapidly collapse to transcytosis NPs(CuS and Au NPs)in TME with cationized surface,which enables excellent transcytosis potential and effectively elevates the penetration of CuS and Au into deep tumor *** the second near-infrared(NIR(II))biowindow laser irradiation,CuS heats the tumor and enhances blood perfusion,eliciting tumor hypoxia alleviation and DNA damage ***,Au NPs enriched in deep tumor tissues effectively sensitize radio-therapeutic *** study provides a new and potential nano-platform to ameliorate tumor hypoxia and sensitize deep tumor tissue radiotherapy.

关键词： breast cancer transcytosis hybrid nanopomegranate hypoxia alleviation radiosensitization

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Light-guided tumor diagnosis and therapeutics:From nanoclusters to polyoxometalates

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Chinese Chemical Letters 2022年第6期33卷 2783-2798页

作者： Xiaofeng Fan Wei Pang Hao Feng Ruiyi Zhang Wentao Zhu Qiushi Wang Jun Miao Yiwen Li Yanjun Liu Xiaoqian Xu key laboratory of Cell Biology Ministry of Public Health and Key Laboratory of Medical Cell BiologyMinistry of EducationChina Medical UniversityShenyang 110122China guangdong provincial key laboratory of Catalysis Shenzhen Grubbs Institute and Department of ChemistrySouthern University of Science and Technology.Shenzhen 518000China School of Materials Science and Engineering Hubei UniversityWuhan 430062China department of Electrical and Electronic Engineering Southern University of Science and TechnologyShenzhen 518000China department of Ophthalmology The First Affiliated Hospital of China Medical UniversityShenyang 110001China

Malignant tumors,with the characteristics of easy metastasis and recurrence,are a serious threat to health of *** is urgent to develop promising clinical cancer targeted agents with combination of rapid diagnosis and efficient *** with the conventional photosensitizing agents,the recent advances of nanoagents based on transition metal-oxide clusters possess unique structural and electronic properties,greatly improving cancer survival rate,meanwhile,keeping high contrast *** review provides a brief introduction of metal-oxide clusters,including both nanoclusters to molecular clusters,specifically polyoxometalates(POMs).Subsequently,biocompatibility of metal-oxide clusters is emphasized from aspects of endocytosis,macropinocytosis,and *** the classification of late and early transition metals oxide clusters,recent outcomes of light-guided nanoagents are represented with their intriguing chemical and optical properties in their diagnosing and photochemotherapy *** shed light on the summary of next generation multifunctional cancer targeting agents'developments as well as outlook of materials selection trends and research direction in the future.

关键词： Polyoxometalates Light-guided nanoagents nanoclusters Metal oxides clusters Photothermal therapy Photodynamic therapy

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tumor microenvironment-responsive hyaluronate-calcium carbonate hybrid nanoparticle enables effective chemo-therapy for primary and advanced osteosarcomas

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nano Research 2018年第9期11卷 4806-4822页

作者： Yi Zhang Lulu Cai Di Li Yeh-Hsing Lao Dingzhuo Liu Mingqiang Li Jianxun Ding Xuesi Chen key laboratory of Polymer Ecomaterials Changchun Institute of Applied Chemistry Chinese Academy of Sciences Changchun 130022 China department of Orthopedics the Fourth Affiliated Hospital of China Medical University Shenyang 110032 China Personalized Drug Therapy key laboratory of Sichuan Province Hospital of the University of Electronic Science and Technology of China Sichuan Provincial People's Hospital Chengdu 610072 China department of Biomedical Engineering Columbia University New York NY 10027 USA guangdong provincial key laboratory of Liver Disease The Third Affiliated Hospital of Sun Yat-sen University Guangzhou 510630 China

Osteosarcoma is the most common malignancy in the bone. Current chemotherapy offers limited efficacy with significant side effects, especially for advanced and relapsed osteosarcomas. nanoparticle-formulated chemotherapeutic drugs may be used to resolve these issues, but several aspects of these formulations remain unsatisfactory, such as how to improve their stability in the bloodstream, prevent undesirable drug leakage, and enhance targeted drug accumulation in the tumor. In this study, a tumor microenvironment-responsive calcium carbonate （CaCO3）- crosslinked hyaluronate （HA） nanopartide was prepared via a ＂green＂ process to effectively deliver doxorubicin （DOX） for the treatment of various stages of osteosarcoma. The DOX-loaded hyaluronate-calcium carbonate hybrid nanoparfide （HA-DOX/CaCO3） demonstrated superior stability both in vitro and in vivo, and rapidly released DOX at the tumor site when triggered by the acidic tumor microenvironment. Compared with free DOX and a non-crosslinked nanoparficle （HA-DOX）, HA-DOX]CaCO3 exhibited the most potent inhibition efficacy toward both primary and advanced models of routine osteosarcoma, resulting in effective tumor inhibition, improved survival time, and reduced adverse effects. Most importantly, in the advanced osteosarcoma model, HA-DOX/CaCO3 potently suppressed tumor growth by 84.6%, which indicates the potential of this platform for osteosarcoma treatment, particularly for advanced and relapsed cases. The proposed polysaccharide nanopartide would be a promising drug delivery platform to advance osteosarcoma nanomedicine.

关键词： hybrid nanomedicine tumor-aridity responsiveness controlled drug delivery multi-stage osteosarcoma chemotherapy

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Platelet membrane-coated C-TiO_(2) hollow nanospheres for combined sonodynamic and alkyl-radical cancer therapy

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nano Research 2023年第1期16卷 782-791页

作者： Weihong Guo Tao Wang Chunyu Huang Shipeng Ning Qinglong Guo Wei Zhang Huawei Yang Daoming Zhu Qinqin Huang Haisheng Qian Xianwen Wang department of Molecular Pathology The Second Affiliated Hospital of Zhengzhou UniversityZhengzhou 450014China department of Orthopaedics The Second Hospital of Anhui Medical UniversityHefei 230601China School of Biomedical Engineering Research and Engineering Center of Biomedical MaterialsAnhui Medical UniversityHefei 230032China department of General Surgery&guangdong provincial key laboratory of Precision Medicine for Gastrointestinal tumor Nanfang HospitalThe First School of Clinical MedicineSouthern Medical UniversityGuangzhou 510515China department of Radiation and Medical Oncology Hubei Key Laboratory of Tumor Biological BehaviorsHubei Cancer Clinical Study CenterZhongnan Hospital of Wuhan UniversityWuhan 430071China department of Breast Surgery Guangxi Medical University Cancer HospitalNanning 530000China

The therapeutic efficiency of sonodynamic therapy(SDT)mainly depends on the presence of oxygen(O_(2))to generate harmful reactive oxygen species(ROS);thus,the hypoxic tumor microenvironment significantly limits the efficacy of ***,the development of oxygen-independent free radical generators and associated combination therapy tactics can be a promising field to facilitate the anticancer capability of *** this study,a biomimetic drug delivery system(C-TiO_(2)/AIPH@PM)composed of an alkyl-radical generator(2,2′-azobis[2-(2-imidazolin-2-yl)propane]dihydrochloride,AIPH)-loaded C-TiO_(2) hollow nanoshells(HNSs)as the inner cores,and a platelet membrane(PM)as the outer shells is successfully prepared for synergistic SDT and oxygen-independent alkyl-radical *** PM encapsulation can significantly prolong the blood circulation time of CTiO_(2)/AIPH@PM compared with C-TiO_(2)/AIPH while enabling C-TiO_(2)/AIPH@PM to achieve tumor targeting.C-TiO_(2)/AIPH@PM can efficiently produce ROS and alkyl radicals,which can achieve a more thorough tumor eradication regardless of the normoxic or hypoxic ***,the generation of these radicals improves the efficiency of *** addition,nitrogen(N_(2))produced due to the decomposition of AIPH enhances the acoustic cavitation effect and lowers the cavitation threshold,thereby enhancing the penetration of CTiO_(2)/AIPH@PM at the tumor *** in vitro and in vivo experiments demonstrate that CTiO_(2)/AIPH@PM possesses good biosafety,ultrasound imaging performance,and excellent anticancer *** study provides a new strategy to achieve oxygen-independent free radical production and enhance therapeutic efficacy by combining SDT and free radical therapy.

关键词： C-TiO_(2) sonodynamic therapy alkyl-radical therapy combination therapy biomimetic nanomaterials

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Overexpression of PITPNM3 promotes hepatocellular carcinoma cell metastasis

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Chinese Science Bulletin 2014年第12期59卷 1326-1333页

作者： Chonghua He Shicheng Su Fei Chen Di Huang Fang Zheng Wei Huang Jianing Chen Xiuying Cui Qiang Liu Erwei Song Herui Yao Yujie Liu guangdong provincial key laboratory of Malignant tumor Epigenetics and Gene Regulation Medical Research CenterSun Yat-Sen Memorial Hospital Sun Yat-Sen University department of Breast Surgery Sun Yat-Sen Memorial HospitalSun Yat-Sen University department of Oncology Sun Yat-Sen Memorial Hospital Sun Yat-Sen University

A previous study indicated that C–C chemokine(C–C motif)ligand 18(CCL18)is capable of inducing tumor cell invasion and metastasis by interacting with receptor membrane-associated phosphatidylinositol transfer protein 3(PITPNM3)in breast cancer *** present study aims to investigate the correlation between the PITPNM3 expression and metastasis in hepatocellular carcinoma(HCC).Real-time quantitative polymerase chain reaction and Western blot were performed to detect the expression pattern of PITPNM3 in patient samples and HCC cell ***-healing and transwell chamber assays were performed to assess the migration and invasiveness of HCC cells,and the activation of the signaling protein downstream of PITPNM3 was also detected by Western blot and *** results revealed that PITPNM3 was upregulated in HCC tissue compared to matched normal liver *** the expression of PITPNM3 by specific siRNAs markedly attenuated the invasive and metastatic abilities of HCC cells,whereas the upregulation of PITPNM3 significantly increased HCC cell ***,inhibiting the expression of PITPNM3 suppressed the activation of Pyk2,FAK,and Src,while overexpression of PITPNM3enhanced the phosphorylation of FAK and Src in HCC ***,suppression of Pyk2 can also impair the clustering of *** results imply that PITPNM3 is a vital determinant of HCC migration and invasion.

关键词：肝癌细胞聚合酶链反应 blot 信号蛋白 Pyk2 乳腺癌细胞磷脂酰肌醇 HCC

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KCTD4 interacts with CLIC1 to disrupt calcium homeostasis and promote metastasis in esophageal cancer

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Acta Pharmaceutica Sinica B 2023年第10期13卷 4217-4233页

作者： Cancan Zheng Xiaomei Yu Taoyang Xu Zhichao Liu Zhili Jiang Jiaojiao Xu Jing Yang Guogeng Zhang Yan He Han Yang Xingyuan Shi Zhigang Li Jinbao Liu Wen Wen Xu key laboratory of Biological Targeting Diagnosis Therapy and Rehabilitation of Guangdong Higher Education Institutesthe Fifth Affiliated Hospital of Guangzhou Medical UniversityGuangzhou 510230China department of Thoracic Surgery Shanghai Chest HospitalSchool of MedicineShanghai Jiao Tong University.Shanghai 200030China department of Radiation Oncology the Fifth Affiliated Hospital of Guangzhou Medical UniversityGuangzhou 510230China department of Thoracic Surgery Sun Yat-sen University Cancer CenterGuangzhou 510060China guangdong provincial key laboratory of Protein Modification and Degradation State Key Laboratory of Respiratory Diseaseand School of Basic Medical SciencesGuangzhou Medical UniversityGuangzhou 511495China

Increasing evidences suggest the important role of calcium homeostasis in hallmarks of cancer,but its function and regulatory network in metastasis remain unclear.A comprehensive investigation of key regulators in cancer metastasis is urgently *** sequencing(RNA-seq)of primary esophageal squamous cell carcinoma(ESCC)and matched metastatic tissues and a series of gain/loss-of-function experiments identified potassium channel tetramerization domain containing 4(KCTD4)as a driver of cancer ***4 expression was found upregulated in metastatic *** KCTD4 expression is associated with poor prognosis in patients with ESCC and contributes to cancer metastasis in vitro and in ***,KCTD4 binds to CLIC1 and disrupts its dimerization,thus increasing intracellular Ca^(2+)level to enhance NFATc1-dependent fibronectin ***4-induced fibronectin secretion activates fibroblasts in a paracrine manner,which in turn promotes cancer cell invasion via MMP24 signaling as positive ***,a lead compound K279-0738 significantly suppresses cancer metastasis by targeting the KCTD4-CLIC1 interaction,providing a potential therapeutic *** together,our study not only uncovers KCTD4 as a regulator of calcium homeostasis,but also reveals KCTD4/CLIC1-Ca^(2+)-NFATc1-fibronectin signaling as a novel mechanism of cancer *** findings validate KCTD4 as a potential prognostic biomarker and therapeutic target for ESCC.

关键词： Cancermetastasis Calcium homeostasis NFAT signaling Fibroblasts Esophageal cancer

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Cerebral corridor creator for resection of trigone ventricular tumors:Two case reports

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World Journal of Clinical Cases 2022年第6期10卷 1914-1921页

作者： Xing-Wu Liu Wei-Rong Lu Tian-Yi Zhang Xu-Sheng Hou Zhi-Qiang Fa Shi-Zhong Zhang department of Functional Neurosurgery The 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 RegenerationZhujiang HospitalSouthern Medical UniversityGuangzhou 510282Guangdong ProvinceChina department of Radiology Zhujiang HospitalSouthern Medical UniversityGuangzhou 510282Guangdong ProvinceChina General Hospital of Xinjiang Military Region Shihezi UniversityUrumqi 830000Xinjiang Uygur Autonomous RegionChina

BACKGROUND Resection of deep intracranial tumors requires significant brain retraction,which frequently causes brain *** particular,tumor in the trigone of the lateral ventricular presents a surgical challenge due to its inaccessible location and intricate adjacent relationships with essential structures such as the optic radiation(OR)*** brain retraction systems have been developed to minimize retraction-associated *** date,there is little evidence supporting the superiority of any retraction system in preserving the white matter tract *** report illustrates the initial surgical excision in two patients using a new retraction system termed the cerebral corridor creator(CCC)and demonstrates its advantage in protecting OR *** SUMMARY We report two patients with nonspecific symptoms,who had trigone ventricular lesions that involved the neighboring OR identified on preoperative diffusion tensor imaging(DTI).Both patients underwent successful surgical excision using the *** tumor removal was achieved without additional neurological *** showed that the OR fibers were preserved along the surgical *** symptoms were alleviated immediately after *** outcomes were improved according to the Glasgow-Outcome-Scale and Activity-of-Daily-Living Scale *** In the two cases,the CCC was a safe and useful tool for creating access to the deep trigonal area while preserving the white matter tract *** CCC is thus a promising alternative brain retractor.

关键词： Cerebral corridor creators Minimally invasive technique Brain tumor Optic radiation Trigone of the lateral ventricle Case report

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Bcl-3 promotes Wnt signaling by maintaining the acetylation ofβ-catenin at lysine 49 in colorectal cancer

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Signal Transduction and Targeted Therapy 2020年第1期5卷 1913-1924页

作者： Xi Chen Chen Wang Yuhang Jiang Qi Wang Yu Tao Haohao Zhang Yongxu Zhao Yiming Hu Cuifeng Li Deji Ye Dandan Liu Wenxia Jiang Eugene Y.Chin Sheng Chen Yongzhong Liu Mingliang Wang Sanhong Liu Xiaoren Zhang CAS key laboratory of Tissue microenvironment and tumor Shanghai Institute of Nutrition and HealthShanghai Institutes for Biological SciencesUniversity of Chinese Academy of SciencesChinese Academy of SciencesShanghai 200025China Shanghai Institute for Advanced Immunochemical Studies ShanghaiTech UniversityShanghai 201210China Affiliated Cancer Hospital&Institute of Guangzhou Medical University Guangzhou Municipal and Guangdong Provincial Key Laboratory of Protein Modification and DegradationState Key Laboratory of Respiratory DiseaseGuangzhou 510000China Renji Hospital Shanghai Jiao Tong University School of MedicineShanghai 200025China State key laboratory of Oncogenes and Related Genes Shanghai Cancer InstituteRenji HospitalShanghai Jiao Tong University School of MedicineShanghai 200032China department of General Surgery Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghai 200025China

Wnt/β-catenin signaling plays a critical role in colorectal cancer(CRC)tumorigenesis and the homeostasis of colorectal cancer stem cells(CSCs),but its molecular mechanism remains unclear.B-cell lymphoma 3(Bcl-3),a member of the IκB family,is overexpressed in CRC and promotes ***,we report a novel function of Bcl-3 in maintaining colorectal CSC homeostasis by activating Wnt/β-catenin *** Bcl-3 suppresses the self-renewal capacity of colorectal CSCs and sensitizes CRC cells to chemotherapeutic drugs through a decrease in Wnt/β-catenin ***,our data show that Bcl-3 is a crucial component of Wnt/β-catenin signaling and is essential forβ-catenin transcriptional activity in CRC ***,Wnt3a increases the level and nuclear translocation of Bcl-3,which binds directly toβ-catenin and enhances the acetylation ofβ-catenin at lysine 49(Ac-K49-β-catenin)and transcriptional ***-3 depletion decreases the Ac-K49-β-catenin level by increasing the level of histone deacetylase 1 to remove acetyl groups fromβ-catenin,thus interrupting Wnt/β-catenin *** CRC clinical specimens,Bcl-3 expression negatively correlates with the overall survival of CRC patients.A significantly positive correlation was found between the expression of Bcl-3 and Ac-K49-β-***,our data reveal that Bcl-3 plays a crucial role in CRC chemoresistance and colorectal CSC maintenance via its modulation of the Ac-K49-β-catenin,which serves as a promising therapeutic target for CRC.

关键词： colorectal homeostasis cancer

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LncRNA CFAR promotes cardiac fibrosis via the miR-449a-5p/LOXL3/mTOR axis

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Science China(Life Sciences) 2023年第4期66卷 783-799页

作者： Mingyu Zhang Bowen Zhang Xiaohan Wang Jiahang Song Ming Tong Zheng Dong Jiaonan Xu Meng Liu Yuan Jiang Ning Wang Ying Wang Zhimin Du Yanyan Liu Rong Zhang Chaoqian Xu department of Pharmacology State-Province Key Laboratories of Biomedicine-Pharmaceutics of ChinaKey Laboratory of Cardiovascular Medicine ResearchMinistry of EducationCollege of PharmacyHarbin Medical UniversityHarbin 150081China department of Pharmacy The Second Affiliated Hospital of Harbin Medical UniversityHarbin 150081China Institute of Clinical Pharmacy The Second Affiliated Hospital of Harbin Medical UniversityHarbin 150081China Zhuhai People’s Hospital Guangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and TreatmentZhuhai Hospital Affiliated with Jinan UniversityJinan UniversityZhuhai 519000China Center of Chronic Diseases and Drug Research of Mudanjiang Medical University Mudanjiang 157011China

Cardiac fibrosis is one of the crucial pathological factors in the heart,and various cardiac conditions associated with excessive fibrosis can eventually lead to heart ***,the exact molecular mechanism of cardiac fibrosis remains *** the present study,we show that a novel lnc RNA that we named cardiac fibrosis-associated regulator(CFAR)is a profibrotic factor in the *** was upregulated in cardiac fibrosis and its knockdown attenuated the expression of fibrotic marker genes and the proliferation of cardiac fibroblasts,thereby ameliorating cardiac ***,CFAR acted as a ce RNA sponge for mi R-449a-5p and derepressed the expression of LOXL3,which we experimentally established as a target gene of mi *** contrast to CFAR,mi R-449a-5p was found to be significantly downregulated in cardiac fibrosis,and artificial knockdown of mi R-449a-5p exacerbated fibrogenesis,whereas overexpression of mi R-449a-5p impeded ***,we found that LOXL3 mimicked the fibrotic factor TGF-β1 to promote cardiac fibrosis by activating m ***,our study established CFAR as a new profibrotic factor acting through a novel mi R-449a-5p/LOXL3/m TOR axis in the heart and therefore might be considered as a potential molecular target for the treatment of cardiac fibrosis and associated heart diseases.

关键词： CFAR miR-449a-5p LOXL3 mTOR cardiac fibrosis

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Systemic delivery of gemcitabine analogue and STAT3 siRNA promotes antitumor immunity against melanoma

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nano Research 2022年第10期15卷 9057-9072页

作者： Huan Yan Zhanyan Liu Guibin Lin Fei Gu Yan Liu Yuxiao Xu Xueli Kuang Yuan Zhang School of Biomedical Sciences and Engineering South China University of TechnologyGuangzhou International CampusGuangzhou 511442China National Engineering Research Center for Tissue Restoration and Reconstruction South China University of TechnologyGuangzhou 510006China 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

Immunosuppressive myeloid cells in the tumor microenvironment(TME)inhibit T-cell-mediated immune response and promote tumor *** targeting both tumor cells and myeloid cells such as myeloid-derived suppressor cells(MDSCs),is expected to promote antitumor ***(Gem)can serve as a chemotherapeutic drug and a MDSCdepleting *** activation of STAT3 promotes tumor cell growth and orchestrates the immunosuppressive activity of tumor-associated myeloid *** we describe a strategy to kill tumor cells as well as inhibit the expansion and suppressive function of myeloid cells through the systemic delivery of gemcitabine monophosphate(GMP)and STAT3 siRNA(siSTAT3).To enhance their in vivo delivery efficiency,we formulate GMP and siSTAT3 into a lipid-coated calcium phosphate(LCP)nanoparticle and a liposome-protamine-hyaluronic acid(LPH)nanoparticle,*** to the control and monotherapy groups,combined GMP and siSTAT3 nanoparticles effectively induced tumor cell death,downregulated a wide range of pro-tumor signaling pathways and immunosuppressive mediators,eliminated MDSCs,enhanced T cell effector functions in tumors and lymphoid compartments,and led to superior therapeutic efficacy in a syngeneic mouse melanoma ***,these nanoparticles can serve as adjuvant treatment to improve the therapeutic response of anti-PD-1-based immune checkpoint blockade ***,the combination of gemcitabine chemotherapy and STAT3 inhibition through nanotechnology could effectively kill tumor cells,alleviate the immunosuppressive TME,and enhance endogenous antitumor immunity.

关键词： immunosuppression tumor microenvironment nanoparticle gemcitabine STAT3 siRNA

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