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Synergistic integration of metal nanoclusters and biomolecules as hybrid systems for therapeutic applications

Acta Pharmaceutica Sinica B 2021年第5期11卷 1175-1199页

作者： Peng Gao Xin Chang Dagan Zhang Yafei Cai Gen Chen Hao Wang Tianfu Wang Guangdong key laboratory of Biomedical Measurements and Ultrasound imaging Department of Biomedical EngineeringShenzhen UniversityShenzhen 518060China State key laboratory of Bioelectronics School of Biological Science and Medical EngineeringSoutheast UniversityNanjing 210096China key laboratory of Biomedicine in Gene Diseases and Health of Anhui Higher Education Institutes College of Life SciencesAnhui Normal UniversityWuhu 241000China College of Animal Science and Technology Nanjing Agricultural UniversityNanjing 210095China School of Materials Science and Engineering Central South UniversityChangsha 410083China College of Energy Soochow Institute for Energy and Materials Innovationsand Key Laboratory of Advanced Carbon Materials and Wearable Energy Technologies of Jiangsu ProvinceSoochow UniversitySuzhou 215006China

Therapeutic nanoparticles are designed to enhance efficacy,real-time monitoring,targeting accuracy,biocompatibility,biodegradability,safety,and the synergy of diagnosis and treatment of diseases by leveraging the unique physicochemical and biological properties of well-developed ***,bio-inspired metal nanoclusters(NCs)consisting of several to roughly dozens of atoms(molecular *** resultant nanoparticles possess combinatorial properties and synergistic efficacy,such as simplicity,active bio-responsiveness,improved applicability,and low cost,for combination therapy,such as accurate targeting,bioimaging,and enhanced therapeutic and biocatalytic *** contrast to larger nanoparticles,bio-inspired metal NCs allow rapid renal clearance and better pharmacokinetics in biological ***,advances in nanoscience,interfacial chemistry,and biotechnologies have further spurred researchers to explore bio-inspired metal NCs for therapeutic *** current review presents a comprehensive and timely overview of various metal NCs for various therapeutic applications,with a special emphasis on the design rationale behind the use of biomolecules/cells as the main *** the different hybrid platform,we summarize the current challenges and emerging perspectives,which are expected to offer in-depth insight into the rational design of bio-inspired metal NCs for personalized treatment and clinical translation.

关键词： Metal nanoclusters Biomolecule Nanoparticles Hybrid system Synergistic properties Fluorescence Bioprobe Therapy

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Carbon-based nanodots for biomedical applications and clinical transformation prospects

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BMEMat(BioMedical Engineering Materials) 2024年第3期2卷 9-27页

作者： Haizhen Ding Tenghui Xiao Fangfang Ren Yu Qiu Zhiyang Shen Xuecheng Chen Ewa Mijowska Hongmin Chen State key laboratory of Vaccines for Infectious Diseases Center for Molecular Imaging and Translational MedicineXiang an Biomedicine LaboratorySchool of Public HealthXiamen UniversityXiamenChina State key laboratory of molecular Vaccinology and molecular Diagnostics National Innovation Platform for Industry-Education Integration in Vaccine ResearchXiamen UniversityXiamenChina Faculty of Chemical Technology and Engineering West Pomeranian University of TechnologySzczecinPoland

Carbon dots(CDs),emerging as a promising class of nanomaterials,have garnered significant interest in the field of biomedicine due to their unique physicochemical *** review provides a comprehensive overview of the recent advancements in the biomedical applications of CDs,emphasizing their potential for revolutionizing diagnostics,therapy,and *** discuss the synthesis and functionalization of CDs,which are pivotal in tailoring their properties for specific biomedical *** applications of CDs in bioimaging include fluorescence imaging,magnetic resonance imaging,photoacoustic imaging,***,this review delves into the benefits of CDs in the treatment of diseases including cancer,inflammation and Alzheimer's,***,we look forward to the future of CDs in the field of biomedicine,emphasizing the necessity of interdisciplinary collaboration to overcome current obstacles and facilitate the clinical translation of CDs-based *** review aims to provide a summary and perspectives on the latest developments of CDs in biomedicine,hoping to inspire further research in this rapidly advancing field.

关键词： bioimaging biomedical applications carbon dots structural design therapy

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Advanced near-infrared light approaches for neuroimaging and neuromodulation

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BMEMat(BioMedical Engineering Materials) 2023年第2期1卷 122-152页

作者： Hongqiang Yin Wuqiao Jiang Yongyang Liu Dongyang Zhang Feng Wu Yejun Zhang Chunyan Li Guangcun Chen Qiangbin Wang CAS key laboratory of Nano-Bio Interface Suzhou Key Laboratory of Functional Molecular Imaging TechnologyDivision of Nanobiomedicine and i-LabSuzhou Institute of Nano-Tech and Nano-BionicsChinese Academy of SciencesSuzhouChina School of Nano-Tech and Nano-Bionics University of Science and Technology of ChinaHefeiChina College of Materials Sciences and Opto-Electronic Technology University of Chinese Academy of SciencesBeijingChina

Almost all physiological processes of animals are controlled by the brain,including language,cognitive,memory,learning,emotion and so *** brain dysfunction usually leads to brain diseases and ***,it'is greatly meaningful and urgent for scientists to have a better understanding of brain structure and *** approaches can provide powerful tools for imaging and modulating physiological processes of the *** particular,optical approaches in the near-infrared(NIR)window(700-1700 nm)exhibit excellent prosperities of deep tissue penetration and low tissue scattering and absorption compared with those of visible windows(400-700 nm),which provides a promising approach for scientists to develop desired methods of neuroimaging and neuromodulation in deep brain *** this review,variable types of NIR light approaches for imaging and modulating neural ions,membrane potential,neurotransmitters,and other critical molecules for brain functions and diseases are *** particular,the latest breakthrough research of brain imaging and brain regulation in the NIR-II window(1000-1700 nm)are ***,we conclude the challenges and prospects of NIR light-based neuroimaging and neuromodulation for both basic brain research and further clinical translation.

关键词： nanoprobes near-infrared light neural ion channels neuroimaging neuromodulation

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肿瘤光学分子影像前沿技术:追求更精准和更灵敏

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Engineering 2015年第3期 69-98页

作者：王坤迟崇巍胡振华刘沐寒惠辉尚文婷彭冬张爽叶津佐刘海哮田捷 key laboratory of molecular imaging Institute of Automation Chinese Academy of Sciences

以新发展的光学多模成像、契伦科夫荧光成像和光学影像手术导航技术为代表的光学分子影像前沿技术,开辟了肿瘤研究、临床转化和医疗实践的新前沿领域。相对于传统成像技术,新技术在活体肿瘤成像上可以提供前所未有的灵敏度和精准度。活... 详细信息

以新发展的光学多模成像、契伦科夫荧光成像和光学影像手术导航技术为代表的光学分子影像前沿技术,开辟了肿瘤研究、临床转化和医疗实践的新前沿领域。相对于传统成像技术,新技术在活体肿瘤成像上可以提供前所未有的灵敏度和精准度。活体肿瘤细胞和分子行为与事件的可视化正在系统地促进人们对肿瘤的深度理解。这些成像技术的新进展正被快速应用于肿瘤诊疗,如对不同肿瘤之间分子异质性信息的动态和量化获取,以及通过实时成像辅助实现更有效的治疗性干预。在分子影像的时代中,光学技术为促进高灵敏度肿瘤诊断和个体化治疗的发展带来了巨大的希望,而这些正是精准医学的终极目标之一。

关键词：光学分子影像多模分子成像光学多模断层成像契伦科夫荧光成像光学影像手术导航

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Integrative Characterization of Immune-relevant Genes in Hepatocellular Carcinoma

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Journal of clinical and translational Hepatology 2021年第3期9卷 301-314页

作者： Wei-Feng Hong Yu-Jun Gu Na Wang Jie Xia Heng-Yu Zhou Ke Zhan Ming-Xiang Cheng Ying Cai Department of Medical imaging The First Affiliated Hospital of Guangdong Pharmaceutical UniversityGuangzhouGuangdongChina Department of Ultrasonic Medicine The First Affiliated Hospital of Sun Yat-Sen UniversityGuangzhouGuangdongChina key laboratory of molecular Biology for Infectious Diseases(Ministry of Education) Institute for Viral HepatitisDepartment of Infectious DiseasesThe Second Affiliated HospitalChongqing Medical UniversityChongqingChina College of Nursing Chongqing Medical UniversityChongqingChina Department of Gastroenterology The Second Affiliated HospitalChongqing Medical UniversityChongqingChina Department of Hepatobiliary Surgery The Second Affiliated HospitalChongqing Medical UniversityChongqingChina Department of Intensive Care Medicine The Second Affiliated HospitalChongqing Medical UniversityChongqingChina

Background and Aims:Tumor microenvironment plays an essential role in cancer development and *** immunotherapy has become a promising approach for the treatment of hepatocellular carcinoma(HCC).We aimed to analyze the HCC immune microenvironment characteristics to identify immune-related genetic ***:key immune-relevant genes(KIRGs)were obtained through integrating the differentially expressed genes of The Cancer Genome Atlas,immune genes from the Immunology Database and Analysis Portal,and immune differentially expressed genes determined by single-sample gene set enrichment analysis *** regression analysis was performed to mine therapeutic target genes.A regulatory network based on KIRGs,transcription factors,and immune-related long non-coding RNAs(IRLncRNAs)was also *** outcomes of risk score model were validated in a testing cohort and in clinical samples using tissue immunohistochemistry *** analysis between risk score and immune checkpoint genes and immune cell infiltration were ***:In total,we identified 21 KIRGs,including programmed cell death-1(PD-1)and cytotoxic T-lymphocyte associated protein 4(CTLA4),and found IKBKE,IL2RG,EDNRA,and IGHA1 may be equally important to PD-1 or ***,KIRGs,various transcription factors,and IRLncRNAs were integrated to reveal that the NRF1-AC127024.5-IKBKE axis might be involved in tumor immunity ***,the immune-related risk score model was established according to KIRGs and key IRLncRNAs,and verified more obvious discriminating power in the testing *** analysis indicated TNFSF4,LGALS9,KIAA1429,IDO2,and CD276 were closely related to the risk score,and CD4 T cells,macrophages,and neutrophils were the primary immune infiltration cell ***:Our results highlight the importance of immune genes in the HCC microenvironment and further unravel the underlying molecular mechanisms in the development of HCC.

关键词： Hepatocellular carcinoma Immune gene Immunotherapy Tumor microenvironment Risk model

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抗SARS-CoV-2变异株的广谱mRNA疫苗RQ3013的临床前研究

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Science Bulletin 2023年第24期68卷 3192-3206,M0006页

作者：谭舒丹赵京华胡雪李玉凤武子涵逯国亮于朝丽杜彬荷刘燕李丽陈煜琛李晔姚艳丰张小宇饶具红高歌彭云刘航袁志明刘佳王倩然胡恒睿高小博周辉俞航徐颖洁余巍冯琳王曼丽单超卢静林金钟 State key laboratory of Genetic Engineering School of Life SciencesZhongshan HospitalFudan UniversityShanghai 200438China Shanghai Institute of Infectious Disease and Biosecurity Fudan UniversityShanghai 200438China Zhangjiang mRNA Innovation and translation Center Fudan UniversityShanghai 200438China State key laboratory of Virology Wuhan Institute of VirologyChinese Academy of SciencesWuhan 430071China Center for Biosafety Mega-Science Wuhan Institute of VirologyChinese Academy of SciencesWuhan 430071China Shanghai RNACure Biopharma Co. Ltd.Shanghai 200438China Shanghai key laboratory for Tumor Microenvironment and Inflammation Department of Biochemistry and Molecular Cell BiologyShanghai Jiao Tong University School of MedicineShanghai 200025China Department of Experimental Research Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South ChinaGuangzhou 510060China

全球SARS-CoV-2病毒的不同变异株导致已接种疫苗的人群中突破性感染的比例上升,迫切需要研发更为有效和广谱的COVID-19疫苗.本研究报告了一项mRNA疫苗RQ3013的临床前研究结果,旨在提供对SARS-CoV-2各种变异株(VOCs)的广谱保护.RQ3013疫... 详细信息

全球SARS-CoV-2病毒的不同变异株导致已接种疫苗的人群中突破性感染的比例上升,迫切需要研发更为有效和广谱的COVID-19疫苗.本研究报告了一项mRNA疫苗RQ3013的临床前研究结果,旨在提供对SARS-CoV-2各种变异株(VOCs)的广谱保护.RQ3013疫苗包含经过假尿苷修饰的mRNA,制备成脂质纳米颗粒的形式.该mRNA编码了SARS-CoV-2的刺突(S)蛋白嵌合体,包含与免疫逃逸有关的重要突变位点.我们在多种动物模型中对RQ3013的免疫原性、保护效果和安全性进行了评估.RQ3013在小鼠、仓鼠和非人灵长类动物(NHP)中引发了显著的免疫反应.它能够诱导高滴度的抗体产生,具备对野生型、B.1.1.7、B.1.351、B.1.617.2和奥密克戎系列变异株的广泛中和能力.在小鼠和NHP中,两剂RQ3013疫苗能够有效保护上呼吸道和下呼吸道免受SARS-CoV-2及其变异株的感染.此外,在NHP中对RQ3013的安全性进行了评估,未观察到不良反应.这些结果为在临床试验中评估RQ3013提供了有力的支持,表明它可能成为对抗COVID-19及其变种的广泛保护的有希望的候选疫苗.

关键词： RQ3013 COVID-19 mRNA vaccine SARS-CoV-2 Chimeric spike

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Noncationic polymer-assisted carrier for nucleic acid drug delivery

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Science China Materials 2024年第12期67卷 3796-3810页

作者： Miao Su Junbin Chen Yueqiang Zhu Chaoran Chen Yuxi Zhang Xianzhu Yang 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

Nucleic acid drugs are emerging as a novel biotherapeutic modality for disease treatment,targeting nucleic acids to regulate the protein translation process and thereby facilitating disease *** hold significant promise in biomedical applications and treatment *** their negative charge,high molecular weight,and hydrophilic properties,nucleic acid drugs require carriers to traverse multiple biological barriers and facilitate intracellular *** material-based carriers present an unprecedented opportunity to address these challenges through electrostatic interactions with nucleic ***,concerns regarding the biosafety and cytotoxic responses of cationic materials have emerged in early clinical *** a result,the use of non-cationic polymer carriers,by controlling or circumventing the use of cationic materials,represents a promising approach for nucleic acid *** this review,we highlight various designs of non-cationic polymer carriers that go beyond the principle of electrostatic interactions,including conjugation,chemical bonding,physical crosslinking,hydrophobic interactions,and coordination bonding with nucleic ***,we discuss strategies for enhancing the efficiency of nucleic acid delivery and therapeutic effects of non-cationic polymer carriers,focusing on targeted delivery,cellular internalization,and endosomal escape.

关键词： nucleic-acid-based therapeutics nucleic acids delivery non-cationic polymer carriers

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Recent developments on PET radiotracers for TSPO and their applications in neuroimaging

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Acta Pharmaceutica Sinica B 2021年第2期11卷 373-393页

作者： Lingling Zhang Kuan Hu Tuo Shao Lu Hou Shaojuan Zhang Weijian Ye Lee Josephson Jeffrey H.Meyer Ming-Rong Zhang Neil Vasdev Jinghao Wang Hao Xu Lu Wang Steven H.Liang Center of Cyclotron and PET Radiopharmaceuticals Department of Nuclear Medicine and PET/CT-MRI CenterThe First Affiliated Hospital of Jinan UniversityGuangzhou 510630China Department of Neurology the First Affiliated Hospital of Jinan UniversityGuangzhou 510630China Department of Radiopharmaceuticals Development National Institute of Radiological SciencesNational Institutes for Quantum and Radiological Science and TechnologyChiba 263-8555Japan Division of Nuclear Medicine and molecular imaging Massachusetts General Hospital&Department of RadiologyHarvard Medical SchoolBostonMA 02114USA Azrieli Centre for Neuro-Radiochemistry Brain Health Imaging CentreCentre for Addiction and Mental Health&Department of PsychiatryUniversity of TorontoToronto ON M5T 1R8Canada Department of Pharmacy the First Affiliated Hospital of Jinan UniversityGuangzhou 510630China

The 18 kDa translocator protein(TSPO),previously known as the peripheral benzodiazepine receptor,is predominately localized to the outer mitochondrial membrane in steroidogenic *** TSPO expression is relatively low under physiological conditions,but is upregulated in response to glial cell *** the primary index of neuroinflammation,TSPO is implicated in the pathogenesis and progression of numerous neuropsychiatric disorders and neurodegenerative diseases,including Alzheimer’s disease(AD),amyotrophic lateral sclerosis(ALS),Parkinson’s disease(PD),multiple sclerosis(MS),major depressive disorder(MDD)and obsessive compulsive disorder(OCD).In this context,numerous TSPO-targeted positron emission tomography(PET)tracers have been *** them,several radioligands have advanced to clinical research *** this review,we will overview the recent development of TSPO PET tracers,focusing on the radioligand design,radioisotope labeling,pharmacokinetics,and PET imaging ***,we will consider current limitations,as well as translational potential for future application of TSPO *** review aims to not only present the challenges in current TSPO PET imaging,but to also provide a new perspective on TSPO targeted PET tracer discovery *** these challenges will facilitate the translation of TSPO in clinical studies of neuroinflammation associated with central nervous system diseases.

关键词： TSPO Microglial activation Neuroinflammation Positron emission tomography(PET) CNS disorders

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HRCT Scans of Peripheral Non-Small Cell Lung Cancers and their Relationship with Cyclin D1 Expression:a Longitudinal Study

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Chinese Journal of clinical Oncology 2008年第3期5卷 172-178页

作者： Shuhua Ma Linfa Wu Xiaomao Xu Hongbo Le Xiaoling Cheng Huihong Zhang Zhengyu Sun Zhaoxin Wang Min Wu Wei Mei Zhiguo Hu Yuguang Li Department of Radiology First Affiliated Hospital Medical College of Shantou University Shantou 515041 Guangdong Province China. Guangdong key laboratory of Medical molecular imaging Shantou 515041 Guangdong Province China. Department of Radiology Second Affiliated Hospital Medical College of Zhongshan University Guangzhou 510120 Guangdong Province China. Department of Radiology First Hospital of Harbin Harbin 150010 Heilongjiang Province. China.

OBJECTIVE To investigate cyclin D1 expression in peripheral lung cancers and its relationship with CT signs and prognosis. METHODS Cyclin D1 expression in peripheral lung cancers and its relationship with the CT imaging and prognosis were analyzed retrospectively by means of SP immunohistochemistry and spiral CT scanning in 92 patients with peripheral lung cancer verified by pathology. RESULTS Cyclin D1 expression was related to deep lobulation,spiculate protuberance,short thin spinules sign and mediastina lymph node *** D1 expression was not related to tumor size,cavity,pleural indentation,histological type,differentiation,tumor TNM stage,age or *** D1 was a negative prognostic factor whose over-expression indicated a poor prognosis. CONCLUSION Cyclin D1 expression may play an important role in the occurrence,progress and CT scan results of lung *** D1 was a negative factor whose over-expression implied a poor *** of the cyclin D1 and observation of the CT scan can be considered as indexes of clinical diagnosis and prognostic evaluation.

关键词： lung neoplasms cyclin D1 computed tomography.

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SLAMF7 Regulates Inflammatory Response In Macrophage During Polymicrobial Sepsis

SLAMF7 Regulates Inflammatory Response In Macrophage During ...

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第十四届全国免疫学学术大会

作者： Yongjian Wu Juanfeng Lao Miao Li Minhao Wu Siqi Ming Lei Liu Sitang Gong Haibo Zhou Xi Huang Center for Infection and Immunity and Guangdong Provincial key laboratory of Biomedical imaging the Fifth Affiliated Hospital of Sun Yat-sen University National clinical Research Center for Infectious Disease Shenzhen Third People's Hospital guangzhou Women and Children's Medical Center Guangzhou Institute of Pediatrics Guangzhou Medical University The Sixth Affiliated Hospital of guangzhou Medical University Qingyuan People's Hospital

Uncontrolled microbe-triggered inflammation Results in multiple organ injury and shock in sepsis. However, the regulatory mechanisms that restrict cytokine storm are still elusive. Using gene screening, we identified an immunoglobulin-like receptor called Signaling Lymphocyte Activation molecular Family-7(SLAMF7), as a key regulator of inflammation during sepsis. We found that the expression of SLAMF7 on monocytes and macrophages was significantly elevated in sepsis subjects and septic mice. SLAMF7 attenuated TLR dependent MAPKs and NF-κB signaling activation by co-operating with Src homology 2-containing inositol-5’-phosphatase1(SHIP1). Furthermore, SLAMF7 interacted with SHIP1 and TNF receptor associated factor 6(TRAF6) to inhibited K63 ubiquitination of TRAF6. In addition, we found that intracellular domain tyrosine phosphorylation sites of SLAMF7 and phosphatase domain of SHIP1 were indispensable for the interaction of SLAMF7/SHIP1/TRAF6 and the modulation of cytokines production. Finally, recombinant murine SLAMF7 peptide agonist or genetic knockout of SLAMF7 in mice demonstrated that SLAMF7 conferred protection against lethal sepsis and endotoxemia by suppressing inflammatory cytokines. Taken together, our findings reveal a critical negative regulatory role of SLAMF7 on cytokine storm in macrophages during polymicrobial sepsis, and therefore provide new sights into a novel diagnostic marker and therapeutic target for sepsis.

关键词： Sepsis SLAMF7 Inflammatory cytokines SHIP1 TRAF6

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