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Tungsten 2025年第1期7卷 183-194页

作者： Xin-Ran Sun Hao-Ming Yuan Guo-Da Zhang Chao Wang Shu-Juan Sun Peng-Fei Shi Shandong Provincial key laboratory of Detection Technology for tumor Markers School of Chemistry and Chemical Engineering Linyi University

The combination of photodynamic therapy（PDT） and chemodynamic therapy（CDT） in tumor treatment has attracted considerable ***,tumor hypoxia and glutathione（GSH） overproduction in the tumor tissue restricted the progress of their ***,a Mn-porphyrinic metal-organic framework（Mn-TCPP） was constructed by the one-pot method and further used for immobilizing glucose oxidase（GOx） to obtain GOx@*** would rapidly exhaust endogenous glucose into hydrogen peroxide（H2O2） and gluconic acid,thus shutting off the energy supply of tumor cells for starvation ***-TCPP catalyzed H2O2to produce oxygen,regulating the hypoxic tumor microenvironment and in turn improving1O2generation under laser ***,Mn-TCPP can reduce reactive oxygen species consumption owing to the redox reaction between Mn3+and GSH,thus greatly enhancing ***,benefiting from GOx-mediated starvation therapy,Mn2+produced by Mn3+reduction can react with sufficient intracellular H2O2to generate ·OH with high cytotoxicity through a Fenton-like *** treatment by GOx@Mn-TCPP under laser irradiation in vitro,the cell viability of 4T1 and A549 tumor cells reached to 20%,reflecting GOx@Mn-TCPP could give full play to the advantages of PDT/CDT/starvation *** results in vivo demonstrated that GOx@Mn-TCPP mediated synergistic cascade therapy could significantly inhibit tumor growth and improve the therapeutic effect.

关键词： Chemodynamic therapy Immobilizing enzyme Metal–organic frameworks Photodynamic therapy Starvation therapy

Exploring the potential of extrachromosomal DNA as a novel oncogenic driver

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Science China Life Sciences 2025年第1期68卷 144-157页

作者： Huanbo Zhu Longtao Huangfu Junbing Chen Jiafu Ji Xiaofang Xing key laboratory of Carcinogenesis and Translational Research (Ministry of Education/beijing) Division of Gastrointestinal Cancer Translational Research LaboratoryPeking University Cancer Hospital & Institute Department of Gastrointestinal Cancer Center Peking University Cancer Hospital & Institute Department of Liver Surgery & Transplantation Liver Cancer InstituteZhongshan HospitalFudan University key laboratory of Carcinogenesis and Cancer Invasion Ministry of Education State key laboratory of Holistic Integrative Management of Gastrointestinal Cancers Beijing Key Laboratory of Carcinogenesis and Translational ResearchDivision of Gastrointestinal Cancer Translational Research LaboratoryPeking University Cancer Hospital & Institute

Extrachromosomal DNA(ecDNA) is a form of circular DNA mostly found in tumor cells. Unlike the typical chromosomal DNA, ecDNA is circular, self-replicating, and carries complete or partial gene fragments. Although ecDNA occurrence remains a rare event in cancer, recent studies have shown that oncogene amplification on ecDNA is widespread throughout many types of cancer, implying that ecDNA plays a central role in accelerating tumor evolution. ecDNA has also been associated with increased tumor mutation burden, chromosomal instability, and even tumor microenvironment remodeling. ecDNA may be crucial in influencing tumor heterogeneity, drug sensitivity,oncogenic senescence, and tumor immunogenicity, leading to a worsening prognosis for tumor patients. In this way, several clinical trials have been conducted to investigate the importance of ecDNA in clinical treatment. In this review, we summarize the biogenesis, characteristics, and current research methods of ecDNA, discuss the vital role of ecDNA-caused tumor heterogeneity in cancers, and highlight the potential role of ecDNA in cancer therapy.

关键词： extrachromosomal DNA cancer therapy tumor heterogeneity drug resistance tumor evolution

Advances in the Development of Gradient Scaffolds Made of Nano‑Micromaterials for musculoskeletal Tissue Regeneration

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Nano-Micro Letters 2025年第3期17卷 455-500页

作者： Lei Fang Xiaoqi Lin Ruian Xu Lu Liu Yu Zhang Feng Tian Jiao Jiao Li Jiajia Xue beijing laboratory of Biomedical Materials Beijing University of Chemical TechnologyBeijing 100029People’s Republic of China State key laboratory of Organic‑Inorganic Composites Beijing University of Chemical TechnologyBeijing 100029People’s Republic of China School of Biomedical Engineering Faculty of Engineering and ITUniversity of Technology SydneySydneyNSW 2007Australia

The intricate hierarchical structure of musculoskeletal tissues,including bone and interface tissues,necessitates the use of complex scaffold designs and material structures to serve as tissue-engineered *** has led to growing interest in the development of gradient bone scaffolds with hierarchical structures mimicking the extracellular matrix of native tissues to achieve improved therapeutic *** on the anatomical characteristics of bone and interfacial tissues,this review provides a summary of current strategies used to design and fabricate biomimetic gradient scaffolds for repairing musculoskeletal tissues,specifically focusing on methods used to construct compositional and structural gradients within the *** latest applications of gradient scaffolds for the regeneration of bone,osteochondral,and tendon-to-bone interfaces are ***,the current progress of testing gradient scaffolds in physiologically relevant animal models of skeletal repair is discussed,as well as the challenges and prospects of moving these scaffolds into clinical application for treating musculoskeletal injuries.

关键词： Gradient scaffolds musculoskeletal tissues Advanced manufacturing Biomaterials Tissue regeneration

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Lung-targeted polyzwitterionic lipid nanoparticles for effective treatment of lung inflammation

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Science China Chemistry 2025年

作者： Wen Zhang Jiaxin Li Nan Wang Muzi Li Chen Peng Xinyue Zhang Guanghui Ouyang Yan Li beijing key laboratory for Bioengineering and Sensing Technology School of Chemistry and Biological Engineering University of Science and Technology Beijing CAS key laboratory of Colloid Interface and Chemical Thermodynamics Institute of Chemistry Chinese Academy of Sciences

Lipid nanoparticles (LNPs) are non-viral nucleic acid delivery systems that show great potential in vaccine development and disease treatment. Although LNPs are particularly advantageous for in vivo delivery, the wide application of LNPs is impeded as their systemic delivery of nucleic acid drugs to extrahepatic tissues remains highly challenging. To address this issue, we developed lung-targeted polyzwitterionic LNPs with zwitterionic polymer poly(2-methyacryloyloxyethyl phosphorylcholine)(PMPC) modified 1,2-dimyristoyl-sn-glycerol lipid for the delivery of small interfering RNA (siRNA). Three libraries with 90PMPC-LNPs@siRNA were established. The polyzwitterionic PMPC-LNPs had high siRNA encapsulation efficiency of about90%. The findings revealed that polyzwitterionic PMPC-LNPs@siRNA absorbed protein corona with the main component of Vitronectin, mediating lung-targeted delivery of siRNA. With good cellular uptake and endo/lysosomal escape ability, in vitro and in vivo studies demonstrated that polyzwitterionic PMPC-LNPs with siRNA against tumor necrosis factor-α (TNF-α) could significantly down-regulate the TNF-α in mRNA and protein levels, and improved the pathological features of lung inflammation. Polyzwitterionic PMPC-LNPs@siRNA achieved safe and efficient treatment of lung inflammation. Therefore, this work offered a promising siRNA therapeutic approach for lung diseases.

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AZD1775 synergizes with SLC7A11 inhibition to promote ferroptosis

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Science China Life Sciences 2025年第1期68卷 204-218页

作者： Chen Xiong Hong Ling Yingdan Huang Hanzhi Dong Bangxiang Xie Qian Hao Xiang Zhou Fudan University Shanghai Cancer Center and Institutes of Biomedical Sciences Fudan University Department of Oncology Shanghai Medical CollegeFudan University Department of Breast Surgery Fudan University Shanghai Cancer CenterFudan University Department of Oncology First Affiliated Hospital of Nanchang University beijing Institute of Hepatology Beijing Youan HospitalCapital Medical University beijing Engineering Research Center for Precision Medicine and Transformation of Hepatitis and Liver Cancer key laboratory of Breast Cancer in Shanghai Fudan University Shanghai Cancer CenterFudan University Shanghai key laboratory of Medical Epigenetics International Co-laboratory of Medical Epigenetics and Metabolism (Ministry of Science and Technology)Institutes of Biomedical SciencesFudan University

tumor suppressor p53-mediated cell cycle arrest and DNA damage repair may exert cytoprotective effects against cancer therapies, including WEE1 inhibition. Considering that p53 activation can also lead to multiple types of cell death, the role of this tumor suppressor in WEE1 inhibitor-based therapies remains disputed. In this study, we reported that nucleolar stress-mediated p53 activation enhanced the WEE1 inhibitor AZD1775-induced ferroptosis to suppress lung cancer growth. Our findings showed that AZD1775 promoted ferroptosis by blocking cystine uptake, an action similar to that of Erastin. Meanwhile, inhibition of WEE1 by the WEE1 inhibitors or si RNAs induced compensatory upregulation of SLC7A11, which conferred resistance to ferroptosis. Mechanistically, AZD1775 prevented the enrichment of H3K9me3, a histone marker of transcriptional repression, on the SLC7A11 promoter by repressing the expression of the histone methyltransferase SETDB1, thereby enhancing NRF2-mediated SLC7A11 transcription. This finding was also validated using the H3K9me3 inhibitor BRD4770. Remarkably, we found that the nucleolar stress-inducing agent Actinomycin D(Act. D) inhibited SLC7A11 expression by activating p53, thus augmenting AZD1775-induced ferroptosis. Moreover, the combination of AZD1775 and Act. D synergistically suppressed wild-type p53-harboring lung cancer cell growth both in vitro and in vivo. Altogether, our study demonstrates that AZD1775 promotes ferroptosis by targeting cystine uptake but also mediates the adaptive activation of SLC7A11 through the WEE1-SETDB1 cascade and NRF2-induced transcription, and inhibition of SLC7A11 by Act. D boosts the anti-tumor efficacy of AZD1775 by enhancing ferroptosis in cancers with wild-type p53.

关键词： p53 NRF2 SLC7A11 WEE1 AZD1775 ferroptosis nucleolar stress

Recent advances in exploring new blood-based biomarkers for the early diagnosis of gastric cancer

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Science China Chemistry 2025年第1期68卷 35-45页

作者： Xinyu Peng Qian Ma Da Han School of Life Science Shanghai University Institute of Molecular Medicine Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine State Key Laboratory of Oncogenes and Related Genes Renji Hospital School of Medicine Shanghai Jiao Tong University Department of Research and Development Intellinosis Biotechnologies Co.Ltd.

Gastric cancer(GC) is a prevalent and lethal malignancy worldwide, and the 5-year survival rate is less than 30%. The absence of distinctive symptoms often leads to late-stage diagnosis, contributing to a grim prognosis. Early detection is pivotal for improving the survival rates and outcomes of GC patients. Traditional diagnostic methods, including gastroscopy and histopathological examination, are restricted in the early diagnosis of GC. Conventional protein biomarkers, such as carcinoembryonic antigen(CEA), carbohydrate antigen 19-9(CA19-9), and carbohydrate antigen 72-4(CA72-4), exhibit insufficient sensitivity and specificity for GC screening, which diminishes their clinical value. Recently, novel circulating biomarkers, such as circulating tumor cells(CTCs), circulating tumor cell DNA(ct DNA), and circulating free RNA(cf RNA), have emerged as promising candidates in the burgeoning field of liquid biopsy due to their superior sensitivity and specificity. This review focuses on the latest research on blood-based biomarkers for GC diagnosis and examines the clinical potentials and challenges associated with these emerging biomarkers.

关键词： gastric cancer early diagnosis blood

Modifying metabolic and immune hallmarks of cancer by a copper complex

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Science China Chemistry 2025年

作者： Chengyan Chu Yunhua Zhang Chengyuan Qian Xiuzhi Yang Yicun Shang Zijian Guo Xiaoyong Wang State key laboratory of Pharmaceutical Biotechnology School of Life Sciences Nanjing University State key laboratory of Coordination Chemistry School of Chemistry and Chemical Engineering Nanjing University

Metabolic adaptation of cancer cells is a key tactic for maintaining their tumorigenicity and viability in the tumor immune microenvironment （TIME）.Concurrent modulation on the metabolic pathway and immune system could change the living condition of cancer cells and potentiate the efficacy of anticancer drugs.A copper complex （DDCu） was designed to influence the energy metabolism of cancer cells and reshape the *** restrained the production and transportation of lactate by inhibiting the expression of lactate dehydrogenase and monocarboxylate transporter 4,thereby altering the metabolic pathway of cancer cells and improving the acidic tumor ***,DDCu was reduced to Cu+by cellular glutathione to react with lipoylated proteins of the tricarboxylic acid cycle and destabilize the Fe–S cluster proteins,leading to the aggregation of dihydrolipoamide S-acetyltransferase and cuproptosis in cancer ***,DDCu promoted the polarization of macrophages from the M2 to M1 phenotype,activated CD4+and CD8+T cells,and reversed the *** a result,DDCu inhibited the tumor growth through a synergy between metabolic regulation and immunomodulation.

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BMPR2 and HIF1-α overexpression in resected osteosarcoma correlates with distant metastasis and patient survival

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Chinese Journal of Cancer Research 2017年第5期29卷 447-454页

作者： Shidong Wang Tingting Ren Yi Huang Xing Bao Kunkun Sun Danhua Shen Wei Guo musculoskeletal tumor Center Peking University People's Hospital beijing key laboratory of musculoskeletal tumor Department of Pathology Peking University People's Hospital

Objective： Bone morphogenetic protein receptor 2（BMPR2） and hypoxia-inducible factor 1-α（HIF1-α） existed abnormal expression in several types of cancer. However, their expressions and related roles in osteosarcoma are largely ***：To investigate the clinical significance of BMPR2 and HIF1-αin osteosarcoma,we analyzed their expression levels in 103 osteosarcoma specimens by ***,we conducted a follow-up to examine the metastatic behavior and overall survival（OS）of osteosarcoma ***：Among 103 tissues,61 cases had BMPR2-positive expression and 57 cases had HIF1-αpositive expression.A significant correlation was noticed between BMPR2 and HIF1-αexpression in osteosarcoma specimens（P=0.035）.Receiver-operating characteristic（ROC）curves were calculated to investigate the predictive value of the two markers in tumor *** means of univariate and multivariate analysis,BMPR2 and HIF1-αexpression,as well as higher tumor grade,were identified as significant risk factors for OS in patients with ***-Meier survival analysis revealed that the patients with BMPR2 and HIF1-αpositive expression had worse OS compared with patients with BMPR2-negative or HIF1-α-negative ***：It can be concluded that BMPR2 and HIF1-αexpression is highly correlated with metastatic behavior in patients with osteosarcoma and can serve as predictive markers for metastasis and OS of these patients.

关键词： BMPR2 HIF1-α immunochemistry osteosarcoma survival

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circT P63-N suppresses the proliferation and metastasis of nasopharyngeal carcinoma via engaging with HSP90AB1 to modulate the YAP1/Hippo signaling pathway

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Science China Life Sciences 2025年

作者： Dan Wang Sicheng Zuo Junshang Ge Hongke Qu Jie Wu Na Yi Lei Shi Yumin Wang Yongzhen Mo Chunmei Fan Yi He Pan Chen Ming Zhou Bo Xiang Wei Xiong Wenjia Guo Zhaoyang Zeng Can Guo NHC key laboratory of Carcinogenesis and Hunan key laboratory of Cancer Metabolism Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine Central South University key laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education Cancer Research Institute and School of Basic Medicine Sciences Central South University Furong laboratory Cancer Research Institute Affiliated Cancer Hospital of Xinjiang Medical University Xinjiang key laboratory of Translational Biomedical Engineering

Circular RNAs(circRNAs) play pivotal roles in the development and progression of various diseases, including malignant tumors. However,the biological functions and the underlying mechanisms of many circRNAs remain elusive. In this study, we identified a novel circRNA,circTP63-N, generated through the splicing of exons 2–4 of the TP63 gene in nasopharyngeal carcinoma(NPC). circTP63-N was found to be downregulated in clinical samples of NPC. Both in vitro and in vivo experiments unequivocally demonstrated that circTP63-N inhibits the proliferation and metastasis of NPC cells. Further investigations revealed that circTP63-N interacted with the HSP90AB1 protein, leading to the recruitment of LATS/YAP1 proteins. This, in turn, induced phosphorylation and ubiquitination-dependent degradation of YAP1, resulting in reduced nuclear translocation of YAP1 and inhibition of the transcriptional activation of downstream oncogenic genes, including INHBA, MMP3, and CCNE2. Our findings highlight the identification of circTP63-N, a novel circRNA encoded by an important tumor-relevant gene TP63 and elucidate its molecular mechanism as a tumor suppressor in NPC. These insights offer novel potential molecular markers and therapeutic targets for the clinical diagnosis and treatment of NPC.

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An NIR-Ⅱ-emissive Ru(Ⅱ) metallacycle for efficient and safe immunotherapy

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Science China Chemistry 2025年第1期68卷 5-7页

作者： Chonglu Li Jianbo Zhan Biao Dong Institute of Health Inspection and Testing Hubei Provincial Center for Disease Control and Prevention State key laboratory on Integrated Optoelectronics College of Electronic Science and Engineering Jilin University

Immunotherapy, as a groundbreaking cancer treatment, has gained considerable attention for its utilization of the body’s immune system to combat tumors [1]. This therapy induces tumor cell apoptosis, triggering a sustained anti-tumor immune response and effectively preventing tumor recurrence and metastasis [2]. The fundamental principle lies in inducing tumor cell death through specific treatment modalities, leading to the release of a cascade of signaling molecules and antigens, thereby mobilizing the immune system to actively identify and attack tumor cells [3].

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