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A multifunctional nanotheranostic agent potentiates erlotinib to EGFR wild-type non-small cell lung cancer

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Bioactive Materials 2022年第7期7卷 312-323页

作者： Duo Wang Jun Zhou Weimin Fang Cuiqing Huang Zerong Chen Meng Fan Ming-Rong Zhang Zeyu Xiao Kuan Hu Liangping Luo Medical imaging Center The First Affiliated Hospital of Jinan UniversityGuangzhou510632PR China the guangzhou key laboratory of molecular and functional imaging for clinical translation Jinan UniversityGuangzhou510632PR China Department of Advanced Nuclear Medicine Sciences Institute of Quantum Medical ScienceNational Institutes for Quantum and Radiological Science and TechnologyChiba263-8555Japan Center for Nanomedicine and Department of Anesthesiology Brigham and Women’s HospitalHarvard Medical SchoolBostonMA02115USA

Epidermal growth factor receptor(EGFR)tyrosine kinase inhibitors(TKI),such as Erlotinib,have demonstrated remarkable efficacy in the treatment of non-small cell lung cancer(NSCLC)patients with mutated ***,the efficacy of EGFR-TKIs in wild-type(wt)EGFR tumours has been shown to be *** that can sensitize Erlotinib to EGFR wild-type NSCLC remain ***,we developed a multifunctional superparamagnetic nanotheranostic agent as a novel strategy to potentiate Erlotinib to EGFR-wt *** results demonstrate that the nanoparticles can co-escort Erlotinib and a vascular epithermal growth factor(VEGF)inhibitor,Bevacizumab(Bev),to EGFR-wt *** nanotheranostic agent exhibits remarkable effects as an inhibitor of EGFR-wt tumour ***,Bev normalizes the tumour embedded vessels,further promoting the therapeutic efficacy of *** addition,the tumour engagement of the nanoparticles and the vascular normalization could be tracked by magnetic resonance imaging(MRI).Collectively,our study,for the first time,demonstrated that elaborated nanoparticles could be employed as a robust tool to potentiate Erlotinib to EGFR-wt NSCLC,paving the way for imaging-guided nanotheranostics for refractory NSCLCs expressing EGFR wild-type genes.

关键词： Non-small cell lung cancer EGFR wild-Type Superparamagnetic iron oxide Erlotinib Bevacizumab Tumour vascular normalization

Optical molecular imaging Frontiers in Oncology: The Pursuit of Accuracy and Sensitivity

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Engineering 2015年第3期1卷 309-323页

作者： Kun Wang Chongwei Chi Zhenhua Hu Muhan Liu Hui Hui Wenting Shang Dong Peng Shuang Zhang Jiezuo Ye Haixiao Liu Jie Tian key laboratory of molecular imaging Institute of Automation Chinese Academy of Sciences

Cutting-edge technologies in optical molecular imaging have ushered in new frontiers in cancer research, clinical translation, and medical practice, as evidenced by recent advances in optical multimodality imaging, Cerenkov luminescence imaging(CLI), and optical imageguided surgeries. New abilities allow in vivo cancer imaging with sensitivity and accuracy that are unprecedented in conventional imaging approaches. The visualization of cellular and molecular behaviors and events within tumors in living subjects is improving our deeper understanding of tumors at a systems level. These advances are being rapidly used to acquire tumor-to-tumor molecular heterogeneity, both dynamically and quantitatively, as well as to achieve more effective therapeutic interventions with the assistance of real-time imaging. In the era of molecular imaging, optical technologies hold great promise to facilitate the development of highly sensitive cancer diagnoses as well as personalized patient treatment—one of the ultimate goals of precision medicine.

关键词： optical molecular imaging multimodality molecular imaging optical multimodality tomography Cerenkov luminescence imaging intraoperative image-guided surgery

Mineral iron based self-assembling: bridging the small molecular drugs and transformative application

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Science Bulletin 2019年第4期64卷 216-218页

作者： En Ren Chengchao Chu Xin Pang Peng Lv Zhao Lei Gang Liu State key laboratory of molecular Vaccinology and molecular Diagnostics & Center for molecular imaging and translational Medicine School of Public Health Xiamen University

The nanoparticle-based treatment and diagnosis of cancer remain challenging in clinical translation, mainly due to the hurdles that can be associated with the development of targeted delivery, biological side effects,... 详细信息

关键词： nanoparticle-based translation poor drug

Computed tomography and photoacoustic imaging guided photodynamic therapy against breast cancer based on mesoporous platinum with insitu oxygen generation ability

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Acta Pharmaceutica Sinica B 2020年第9期10卷 1719-1729页

作者： Lingyan Zhang Mifang Li Quan Zhou Meng Dang Yuxia Tang Shouju Wang Jijun Fu Zhaogang Teng Guangming Lu Department of Medical imaging Jinling HospitalThe First School of Clinical MedicineSouthern Medical UniversityNanjing 210002China Department of Medical imaging The Third Affiliated HospitalSouthern Medical UniversityGuangzhou 510630China key laboratory for Organic Electronics&Information Displays and Institute of Advanced Materials Jiangsu Key Laboratory for BiosensorsJiangsu National Synergetic Innovation Centre for Advanced MaterialsNanjing University of Posts and TelecommunicationsNanjing 210046China Departm ent of Medical imaging Jiangsu Province HospitalNanjing 210029China key laboratory of molecular Target&clinical Pharmacology School of Pharmaceutical SciencesGuangzhou Medical UniversityGuangzhou 511436China

Photodynamic therapy(PDT)has been widely used in cancer ***,hypoxia in most solid tumors seriously restricts the efficacy of *** improve the hypoxic microenvironment,we designed a novel mesoporous platinum(mPt)nanoplatform to catalyze hydrogen peroxide(H2 O2)within the tumor cells in situ without an extra *** the fabrication,the carboxy terminus of the photosensitizer chlorin e6(Ce6)was connected to the amino terminus of the bifunctional mercaptoaminopolyglycol(SH-PEG-NH2)by a condensation reaction,and then PEG-Ce6 was modified onto the mPt moiety via the mercapto terminal of ***,cellular and animal experiments demonstrated that Pt@PEG-Ce6 catalyzed H2 O2 to produce oxygen(O2)and that Ce6 transformed O2 to generate reactive oxygen species(ROS)upon laser *** Pt@PEG-Ce6 nanoplatform with uniform diameter presented good biocompatibility and efficient tumor *** to the high atomic number and good near-infrared absorption for Pt,this Pt@PEG-Ce6 nanoplatform showed computed tomography(CT)and photoacoustic(PA)dual-mode imaging ability,thus providing an important tool for monitoring the tumor hypoxic ***,the Pt@PEG-Ce6 nanoplatform reduced the expression of hypoxia-inducible factor-la(HIF-1α)and programmed death-1(PD-1)in tumors,discussing the relationship between hypoxia,PD-1,and PDT for the first time.

关键词： Mesoporous platinum Photodynamic therapy Tumor hypoxia Photoacoustic imaging Computed tomography imaging

Acceptor-engineering tailored type-Ⅰ photosensitizer with aggregation-induced NIR-II emission for cancer multimodal phototheranostics

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Science China Chemistry 2024年第8期67卷 2647-2660页

作者： Jiangao Li Niu Niu Deliang Wang Xue Liu Yi Qin Lei Wang Ben Zhong Tang Dong Wang Center for AIE Research Shenzhen Key Laboratory of Polymer Science and TechnologyGuangdong Research Center for Interfacial Engineering of Functional MaterialsCollege of Materials Science and EngineeringShenzhen UniversityShenzhen 518060China guangzhou Municipal and Guangdong Provincial key laboratory of molecular Target Clinical Pharmacologythe State Key Laboratory of Respiratory DiseaseSchool of Pharmaceutical Sciences and the Fifth Affiliated HospitalGuangzhou Medical UniversityGuangzhou 511436China School of Science and Engineering Shenzhen Institute of Aggregate Science and TechnologyThe Chinese University of Hong KongShenzhen(CUHK-Shenzhen)Shenzhen 518172China

Exploration of single molecular species synchronously featured by long excitation/emission wavelength, accurate diagnosis, and effective therapy, remains supremely appealing to implement high-performance cancer phototheranostics. However, those previously established phototheranostic agents are undiversified and stereotyped in terms of structural skeleton, and generally exhibit insufficient phototheranostic outcomes. Herein, we innovatively utilized indanone-condensed thiadiazolo[3,4-g]quinoxaline(ITQ) as electron acceptor to construct novel photosensitizer with second near-infrared(NIR-II) emission. Experimental study and theoretical calculation demonstrated that comparing with the counterparts constituting by widely employed NIR-II building block benzobisthiadiazole(BBTD) and 6,7-diphenylthiadiazoloquinoxaline(DPTQ), ITQ-based photosensitizer(TITQ) showed superior aggregation-induced emission(AIE) characteristics, much stronger type-I reactive oxygen species(ROS) production, and prominent photothermal conversion capacity. Furthermore, TITQ nanoparticles with excellent biocompatibility were capable of effectively accumulating in the tumor site and visualizing tumor through fluorescence-photoacoustic-photothermal trimodal imaging with highly spatiotemporal resolution, and completely eliminating tumor by type-I photodynamic-photothermal therapy.

关键词： phototheranostics aggregation-induced emission NIR-Ⅱfluorescence acceptor engineering photodynamic-photothermal therapy

Construction of a biotin-targeting drug delivery system and its near-infrared theranostic fluorescent probe for real-time image-guided therapy of lung cancer

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Chinese Chemical Letters 2022年第3期33卷 1567-1571页

作者： Xinyu Song Rui Wang Junfang Gao Xiaoyue Han Jianfeng Jin Changjun Lv Fabiao Yu Department of Respiratory Medicine Department of Pediatric Gastroenterology and NephrologyBinzhou Medical University HospitalBinzhou 256603China key laboratory of Hainan Trauma and Disaster Rescue Department of NeurologyThe First Affiliated Hospital of Hainan Medical UniversityHainan Medical UniversityHaikou 571199China key laboratory of Emergency and Trauma Ministry of EducationKey Laboratory of Hainan Functional Materials and Molecular ImagingCollege of PharmacyCollege of Emergency and TraumaHainan Medical UniversityHaikou 571199China State key laboratory of Respiratory Disease National Clinical Research Center for Respiratory DiseaseGuangzhou Institute of Respiratory Healththe First Affiliated Hospital of Guangzhou Medicine UniversityGuangzhou 510120China

The therapy of non-small lung cancer(NSCLC) is limited by wide metastasis and chemotherapy resistance, herein, we present a new cancer-targeting prodrug PBG with the integration of real-time fluorescence visualization. The potent anticancer drug Gefitinib conjugates a biotin recognition ligand yielding the prodrug PBG via a GSH-activatable disulfide bond linker. Once coupling a near-infrared azo-BODIPY fluorophore into the molecular structure of PBG, we obtain its fluorescent theranostic TBG. The prodrug PBG can sustain Gefitinib release by the high level of GSH in the pathophysiological milieu. We evaluate the drug delivery of the prodrug PBG using fluorescent TBG in PC9 cancer bearing nude mice models,which indicate that TBG can be utilized to monitor the in vivo drug release process. Prodrug PBG can be targeted to accumulate in the cancer lesion with a better and efficaciously therapeutic result compared with the single Gefitinib treatment in cells and in vivo. The fluorescence images also reveal that the targeting accumulation and longitudinal retention of anticancer drug in cancer lesions will contribute to the superior therapeutic effects. The above applications of our new prodrug PBG and its fluorescent theranostic TBG have the potential contribution to the research in biology and the clinical medicine.

关键词： Fluorescent probe Drug delivery Theranostics In vivo imaging Lung cancer

Evolution of the newest diagnostic methods for COVID-19:a Chinese perspective

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2023年第6期24卷 463-484页

作者： Mingtao LIU Jiali LYU Xianhui ZHENG Zhiman LIANG Baoying LEI Huihuang CHEN Yiyin MAI Huimin HUANG Baoqing SUN Department of clinical laboratory National Center for Respiratory MedicineNational Clinical Research Center for Respiratory DiseaseState Key Laboratory of Respiratory DiseaseGuangzhou Institute of Respiratory Healththe First Affiliated Hospital of Guangzhou Medical UniversityGuangzhou510140China National Center for Respiratory Medicine National Clinical Research Center of Respiratory DiseaseState Key Laboratory of Respiratory DiseaseGuangzhou Institute of Respiratory Healththe First Affiliated Hospital of Guangzhou Medical UniversityGuangzhou 510140China guangzhou Medical University Guangzhou 511495China

Coronavirus disease 2019(COVID-19)has continued to spread globally since late 2019,representing a formidable challenge to the world's healthcare systems,wreaking havoc,and spreading rapidly through human *** fever,fatigue,and a persistent dry cough being the hallmark symptoms,this disease threatened to destabilize the delicate balance of our global *** and accurate diagnosis of COVID-19 is a prerequisite for understanding the number of confirmed cases in the world or a region,and an important factor in epidemic assessment and the development of control *** also plays a crucial role in ensuring that patients receive the appropriate medical treatment,leading to optimal patient *** transcription-polymerase chain reaction(RT-PCR)technology is currently the most mature method for detecting viral nucleic acids,but it has many ***,a variety of COVID-19 detection methods,including molecular biological diagnostic,immunodiagnostic,imaging,and artificial intelligence methods have been developed and applied in clinical practice to meet diverse scenarios and *** methods can help clinicians diagnose and treat COVID-19 *** review describes the variety of such methods used in China,providing an important reference in the field of the clinical diagnosis of COVID-19.

关键词： Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) Coronavirus disease 2019(COVID-19) Diagnosis Polymerase chain reaction(PCR) Immunoassay Radiography

Metal-based nanoparticles for cardiovascular disease diagnosis and therapy

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Particuology 2023年第1期72卷 94-111页

作者： Lei Li Yun Zeng Gang Liu State key laboratory of molecular Vaccinology and molecular Diagnostics Center for Molecular Imaging and Translational MedicineSchool of Public HealthXiamen UniversityXiamen 361102China Department of Pharmacy Xiamen Medical CollegeXiamen 361023China

Cardiovascular diseases (CVDs) are the most prominent cause of disability and mortality in the world. Although there have been a variety of therapeutic options for the management of CVDs, most of the traditional therapeutic strategies could not sufficiently stop or reduce the progression of these diseases and may result in some side effects. With the advance in nanotechnology, a number of metal-based nanoparticles have been developed and shown promising potentials in the treatment of CVDs. In this review, we provide a comprehensive review of researches on recent development of metal-based nanoparticles in diagnosis and therapy in CVDs as biomedical materials. We also discuss the challenges in the clinical translation and potential risks in their application of CVD therapy. Based on the ongoing research and applications, we can conclude metal-based nanoparticles are expected to become potential therapeutics for the treatment of CVDs. But their application is still in its infancy and much more efforts should be made to enforce a clinical breakthrough.

关键词： Metal-based nanoparticles Nanomedicine Cardiovascular diseases Diagnosis Therapy

TREM-2 Drives Development of Multiple Sclerosis by Promoting Pathogenic Th17 Polarization

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Neuroscience Bulletin 2024年第1期40卷 17-34页

作者： Siying Qu Shengfeng Hu Huiting Xu Yongjian Wu Siqi Ming Xiaoxia Zhan Cheng Wang Xi Huang Center for Infection and Immunity and Guangdong Provincial Engineering Research Center of molecular imaging The Fifth Affiliated Hospital of Sun Yat-sen UniversityZhuhai 519000China The State key laboratory of Respiratory Disease Guangdong Provincial Key Laboratory of Allergy and Clinical ImmunologyThe Second Affiliated HospitalGuangzhou Medical UniversityGuangzhou 510260China Department of laboratory Medicine The First Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510080China Division of Nephrology Department of Medicinethe Fifth Affliated Hospital of Sun Yat-sen UniversityZhuhai 519000China

Multiple sclerosis(MS)is a neuroinflammatory demyelinating disease,mediated by pathogenic T helper 17(Th17)***,the therapeutic effect is accompa-nied by the fluctuation of the proportion and function of Th17 cells,which prompted us to find the key regulator of Th17 differentiation in ***,we demonstrated that the triggering receptor expressed on myeloid cells 2(TREM-2),a modulator of pattern recognition receptors on innate immune cells,was highly expressed on pathogenic CD4-positive T lymphocyte(CD4^(+)T)cells in both patients with MS and experimental autoimmune encephalomyelitis(EAE)mouse *** knockout of Trem-2 in CD4^(+)T cells significantly alleviated the disease activity and reduced Th17 cell infiltration,activation,differentiation,and inflammatory cytokine production and secretion in EAE ***,with Trem-2 knockout in vivo experiments and in vitro inhibitor assays,the TREM-2/zeta-chain associated protein kinase 70(ZAP70)/signal transducer and activator of transcription 3(STAT3)signal axis was essential for Th17 activation and differentiation in EAE *** conclusion,TREM-2 is a key regulator of pathogenic Th17 in EAE mice,and this sheds new light on the potential of this therapeutic target for MS.

关键词： Multiple sclerosis Experimental autoimmune encephalomyelitis T helper 17 Triggering receptor expressed on myeloid cells 2