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一种乳酸菌-金属有机框架复合物用于强化肿瘤乏氧光动力和免疫治疗

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Science China Materials 2023年第1期66卷 363-374页

作者：李田忠王金勇陈桐楷 Swelm Wageh Ahmed AAl-Ghamdi 于江天谢中建张晗 Interdisciplinary Center of High Magnetic Field Physics of shenzhen University College of Physics and Optoelectronic EngineeringDepartment of OtolaryngologyShenzhen Institute of Translational MedicineShenzhen Second People’s Hospitalthe First Affiliated HospitalShenzhen UniversityShenzhen 518060China Shenzhen International Institute for Biomedical Research Shenzhen 518000China Science and Technology Innovation Center Guangzhou University of Chinese MedicineGuangzhou 510405China Department of Physics Faculty of ScienceKing Abdulaziz UniversityJeddah 21589Saudi Arabia institute of Pediatrics Shenzhen Children’s HospitalShenzhen 518038China

开发长期有效的癌症治疗技术仍然是科研工作者和临床医生面临的重要任务.厌氧型乳酸菌(LAB)具有天然的乏氧倾向性,可自发富集在缺氧的肿瘤微环境中.金属有机框架(MOF)是一类独特的纳米材料,其中的ZIF-67可以自发分解过氧化氢产氧,且析... 详细信息

开发长期有效的癌症治疗技术仍然是科研工作者和临床医生面临的重要任务.厌氧型乳酸菌(LAB)具有天然的乏氧倾向性,可自发富集在缺氧的肿瘤微环境中.金属有机框架(MOF)是一类独特的纳米材料,其中的ZIF-67可以自发分解过氧化氢产氧,且析氧能力可被光照增强.然而,LAB或MOF单独应用于肿瘤治疗的效果并不令人满意.在本文中,我们制备了一种MOF修饰的乳酸菌制剂,用以在缺氧性肿瘤中局部产生活性氧(ROS)助力光动力治疗,同时精准诱导宿主肿瘤免疫.这些细菌表面被ZIF-67纳米材料修饰(LAB@ZIF-67),经体内循环后富集在肿瘤微环境中.细菌表面的ZIF-67可以被CT-26细胞吸收,并且在光照后检测到细胞内快速生成ROS.体内实验表明,该细菌复合物可通过光动力疗法消灭肿瘤,同时诱导肿瘤特异的炎性反应,招募巨噬细胞和T细胞实现肿瘤的免疫治疗.此类材料-细菌复合物为今后研发肿瘤主动靶向药物和癌症免疫疗法提供了新思路.

关键词：肿瘤微环境金属有机框架光动力免疫治疗肿瘤免疫缺氧性巨噬细胞厌氧型

Termination of Transcription of LAT Increases the Amounts of ICP0 mRNA but Does Not Alter the Course of HSV-1 Infection in Latently Infected Murine Ganglia

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Virologica Sinica 2021年第2期36卷 264-272页

作者： Haifang Jiang Jiaming Wu Xianjie Liu Ruitao Lu Manling Zhou Meiling Chen Yonghong Liu Grace Guoying Zhou Wenmin Fu School of Basic Medical Sciences Guangzhou Medical UniversityGuangzhou 511436China Shenzhen International Institute for Biomedical Research Shenzhen 518116China

On entering sensory ganglia,herpes simplex viruses 1(HSV-1)establishes a latent infection with the synthesis of a latency associated transcript(LAT)or initiates productive infection with expression of a set of immediate early viral proteins.The precise mechanisms how expression of a genes is suppressed during the latency are unknown.One mechanism that has been proposed is illustrated in the case of ICP0,a key immediate early viral regulatory protein.Specifically,the 2 kb LAT intron is complementary to the 30 terminal portion of ICP0 m RNA.To test the hypothesis that accumulation of LAT negatively affects the accumulation of ICP0 m RNA,we inserted a DNA fragment encoding two poly(A)sequences into LAT to early terminate LAT transcript without interrupting the complementary sequence of ICP0 transcript(named as SR1603).Comparisons of the parent(SR1601)and mutant(SR1603)HSV-1 viruses showed the following:Neurons harboring latent SR1603 virus accumulated equivalent amounts of viral DNA but higher amounts of ICP0 m RNA and lower amounts of LAT,when compared to neurons harboring the SR1601 virus.One notable difference between the two viruses is that viral RNA accumulation in explanted ganglia harboring SR1603 virus initiated significantly sooner than that in neurons harboring SR1601 virus,suggesting that ICP0 may act as an activator of viral gene expression in permissive cells.Collectively,these data suggest that increased ICP0 m RNA by suppressed LAT did not affect the establishment of latency in latently infected murine ganglia.

关键词： Herpes simplex viruses 1(HSV-1) Latency associated transcript(LAT) ICP0 Latency

Effect of Loss-of-function of the Herpes Simplex Virus-1 microRNA H6-5p on Virus Replication

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Virologica Sinica 2019年第4期34卷 386-396页

作者： Rongquan Huang Xusha Zhou Shuqi Ren Xianjie Liu Zhiyuan Han Grace Guoying Zhou School of Basic Medical Sciences Guangzhou Medical UniversityGuangzhou 511436China Shenzhen International Institute for Biomedical Research Shenzhen 518116China

To date, 29 distinct microRNAs(miRNAs) have been reported to be expressed during herpes simplex virus infections.Sequence analysis of mature herpes simplex virus-1(HSV-1) miRNAs revealed five sets of miRNAs that are complementary to each other: miR-H6-5p/H1-3p, miR-H6-3p/H1-5p, H2-5p/H14-3p, miR-H2-3p/H14-5p, and miR-H7/H27.However, the roles of individual miRNAs and consequences of this complementarity remain unclear. Here, we focus on two of these complementary miRNAs, miR-H6-5p and miR-H1-3p, using loss-of-function experiments in vitro and in a mouse model of infection using an miRNA sponge approach, including tandem multiplex artificial miRNA-binding sequences that do not match perfectly to the target miRNA inserted downstream of a green fluorescent protein reporter gene. Infection with recombinant virus expressing the miR-H6-5p sponge reduced viral protein levels and virus yield.Decreased accumulation of viral proteins was also observed at early stages of infection in the presence of both an miR-H6-5p inhibitor and plasmid-expressed miR-H1-3p. Moreover, establishment of latency and reactivation did not differ between the recombinant virus expressing the miR-H6-5p sponge and wild-type HSV-1. Taken together, these data suggest that miR-H6-5p has an as-yet-unidentified role in the early stages of viral infection, and its complement miR-H1-3p suppresses this role in later stages of infection. This report extends understanding of the roles of miRNAs in infection by herpes simplex viruses, supporting a model of infection in which the production of virus and its virulent effects are tightly controlled to maximize persistence in the host and population.

关键词： miR-H6-5p miR-H1-3p Sponge Replication Herpes simplex virus-1(HSV-1)

Graphene-based nanomaterials for cancer therapy and anti-infections

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Bioactive Materials 2022年第8期7卷 335-349页

作者： Yan Wang Juan Li Xiaobin Li Jinping Shi Zhaotan Jiang Can Yang Zhang School of Physics Beijing Institute of TechnologyBeijing100081China Advanced research institute for Multidisciplinary Science Beijing Institute of TechnologyBeijing100081China institute of Biopharmaceutical and Health Engineering Shenzhen International Graduate SchoolTsinghua UniversityShenzhen518055China

Graphene-based nanomaterials(GBNMs)has been thoroughly investigated and extensively used in many biomedical fields,especially cancer therapy and bacteria-induced infectious diseases treatment,which have attracted more and more attentions due to the improved therapeutic efficacy and reduced reverse effect.GBNMs,as classic two-dimensional(2D)nanomaterials,have unique structure and excellent physicochemical properties,exhibiting tremendous potential in cancer therapy and bacteria-induced infectious diseases treatment.In this review,we first introduced the recent advances in development of GBNMs and GBNMs-based treatment strategies for cancer,including photothermal therapy(PTT),photodynamic therapy(PDT)and multiple combination therapies.Then,we surveyed the research progress of applications of GBNMs in anti-infection such as antimicrobial resistance,wound healing and removal of biofilm.The mechanism of GBNMs was also expounded.Finally,we concluded and discussed the advantages,challenges/limitations and perspective about the development of GBNMs and GBNMs-based therapies.Collectively,we think that GBNMs could be potential in clinic to promote the improvement of cancer therapy and infections treatment.

关键词： Graphene Phototherapy Cancer therapy Anti-infection 2D materials

Preclinical evaluation and pilot clinical study of [^(18)F]AlF-labeled FAPI-tracer for PET imaging of cancer associated fibroblasts

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Acta Pharmaceutica Sinica B 2022年第2期12卷 867-875页

作者： Kongzhen Hu Junqi Li Lijuan Wang Yong Huang Li Li Shimin Ye Yanjiang Han Shun Huang Hubing Wu Jin Su Ganghua Tang Department of Nuclear Medicine Nanfang HospitalSouthern Medical UniversityGuangzhou 510515China Shenzhen International Institute for Biomedical Research Shenzhen 518116China National Cancer Center/National Clinical research Center for Cancer/Cancer Hospital&shenzhen Hospital Chinese Academy of Medical Sciences and Peking Union Medical CollegeShenzhen 518116China State Key Laboratory of Respiratory Disease National Clinical Research Center for Respiratory DiseaseGuangzhou Institute of Respiratory Healththe First Affiliated Hospital of Guangzhou Medical UniversityGuangzhou 510182China

In recent years,fibroblast activation protein(FAP)has emerged as an attractive target for the diagnosis and radiotherapy of cancers using FAP-specific radioligands.Herein,we aimed to design a novel^(18)Flabeled FAP tracer([^(18)F]Al F-P-FAPI)for FAP imaging and evaluated its potential for clinical application.The[^(18)F]Al F-P-FAPI novel tracer was prepared in an automated manner within 42 min with a non-decay corrected radiochemical yield of 32±6%(n=8).Among A549-FAP cells,[^(18)F]Al F-P-FAPI demonstrated specific uptake,rapid internalization,and low cellular efflux.Compared to the patent tracer[^(18)F]FAPI-42,[^(18)F]Al F-P-FAPI exhibited lower levels of cellular efflux in the A549-FAP cells and higher stability in vivo.Micro-PET imaging in the A549-FAP tumor model indicated higher specific tumor uptake of[^(18)F]Al F-P-FAPI(7.0±1.0%ID/g)compared to patent tracers[^(18)F]FAPI-42(3.2±0.6%ID/g)and[68 Ga]Ga-FAPI-04(2.7±0.5%ID/g).Furthermore,in an initial diagnostic application in a patient with nasopharyngeal cancer,[^(18)F]Al F-P-FAPI and[^(18)F]FDG PET/CT showed comparable results for both primary tumors and lymph node metastases.These results suggest that[^(18)F]Al F-P-FAPI can be conveniently prepared,with promising characteristics in the preclinical evaluation.The feasibility of FAP imaging was demonstrated using PET studies.

关键词： Fibroblast activation protein [^(18)F]AlF-P-FAPI PET Nasopharyngeal cancer

Recent Advance of Tellurium for biomedical Applications

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Chemical research in Chinese Universities 2020年第4期36卷 551-559页

作者： WANG Hengliang CHAI Luxiao XIE Zhongjian ZHANG Han international Collaborative Laboratory of 2D Materials for Optoelectwnic Science and Technology Institute of Microscale OptoelectronicsShenzhen UniversityShenzhen 518060P.R.China Shenzhen International Institute for Biomedical Research Shenzhen 518116P.R.China Key Laboratory of Optoelectronic Devices and Systems of Ministry of Education and Guangdong Province Institute of Microscale Optoelectwnics and Otolaryngology Departmentand Biobank of the First Affiliated HospitalShenzhen Second People's HospitalHealth Science CenterShenzhen UniversityShenzhen 518060P.R.China

Tellurium(Te)nanomaterials have aroused a wide interest in semiconductor,thermoelectric,piezoelectric,as well as biomedical applications.The last decades of reports indicated a major nanostructure of one-dimensional(ID)Te on account of its inherent structural anisotropy.Two-dimenional(2D)Te has been newly developed and drawn a lot of interests recently.This review presents the intrinsic biological potential of Te-based nanomaterials and summarizes their up-to-date advance in phototherapy and reactive oxygen species(ROS)-related applications in the biomedical field.

关键词： Tellurium Nanostructure biomedical application

Robust boron nanoplatform provokes potent tumoricidal activities via inhibiting heat shock protein

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Asian Journal of Pharmaceutical Sciences 2022年第5期17卷 728-740页

作者： Yuying Zhao Ning Liu Piaoxue Liu Taojian Fan Rui Ma Huijie Hong Xiaojia Chen Zhongjian Xie Han Zhang Qi Wang Tongkai Chen Science and Technology Innovation Center Guangzhou University of Chinese MedicineGuangzhou 510405China institute of Microscale Optoelectronics Collaborative Innovation Centre for Optoelectronic Science&TechnologyKey Laboratory of Optoelectronic Devices and Systems of Ministry of Education and Guangdong ProvinceCollege of Physics and Optoelectronic EngineeringShenzhen Key Laboratory of Micro-Nano Photonic Information TechnologyGuangdong Laboratory of Artificial Intelligence and Digital Economy(SZ)Shenzhen UniversityShenzhen 518060China College of Health Science and Environmental Engineering School of Shenzhen Technology UniversityShenzhen 518118China State Key Laboratory of Quality research in Chinese Medicine Institute of Chinese Medical SciencesUniversity of MacaoMacao 999078China institute of Pediatrics Shenzhen Children’s HospitalShenzhen 518038China Shenzhen International Institute for Biomedical Research Shenzhen 518116China

Near-infrared(NIR)-light-triggered photothermal therapy(PTT)is a promising treatment for breast cancer.However,its therapeutic efficiency is often compromised due to the heatinduced up-regulation of heat shock proteins,which confer photothermal resistance.To solve this urgent problem,PEGylated two-dimensional boron nanosheets(B-PEG)-which allow both multimodal imaging and photothermal conversion-were loaded with gambogic acid(GA),which can inhibit heat shock protein 90(Hsp90).Experimental findings indicated that this combination of B-PEG and GA could serve as an integrated drug delivery system for cancer diagnosis and treatment.It could be used to administer mild PTT as well as chemotherapy for breast cancer,provide improved anti-tumor effects,and reduce the toxicity of PTT,all while inhibiting breast cancer growth.This drug delivery system could offer a novel tool for administering chemotherapy combined with PTT while avoiding the adverse effects of traditional PTT.

关键词： Mild photothermal therapy Chemotherapy Boron nanosheets Heat shock proteins Breast cancer

Unraveling the interfacial effect of PdBi bimetallic catalysts on promoting CO_(2)electroreduction to formate

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Nano research 2023年第8期16卷 10822-10831页

作者： Wenhui Liu Lingtong Ding Minmin Liu Xiao Wang Zhengrong Zhang Tian-Wen Jiang Shengjuan Huo Wen-Bin Cai international Joint Laboratory of Catalytic Chemistry Department of ChemistryInstitute for Sustainable EnergyCollege of SciencesShanghai UniversityShanghai 200444China shenzhen Key Laboratory of Nanobiomechanics Shenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhen 518055China Paul C.Lauterbur research Center for biomedical Imaging Shenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhen 518055China Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials Collaborative Innovation Center of Chemistry for Energy MaterialsDepartment of ChemistryFudan UniversityShanghai 200438China

Through interface engineering and content control strategy,a PdBi bimetallic interface structure was constructed for the first time to selectively convert CO_(2)to formate with a remarkably high Faraday efficiency(FEformate)of 94%and a partial current density(jformate)of 34 mA·cm^(−2)at−0.8 V vs.reversible hydrogen electrode(RHE)in an H-cell.Moreover,the PdBi interface electrocatalyst even exhibited a high current density of 180 mA·cm^(−2)with formate selectivity up to 92%in a flow cell and could steadily operate for at least 20 h.Electrochemical in-situ attenuated total reflection surface enhanced infrared absorption spectroscopy(ATR-SEIRAS)confirmed that the PdBi interface could greatly weaken the adsorption of*CO intermediates due to electronic and geometric effects.Density functional theory(DFT)calculations also established that the PdBi interface regulated the CO_(2)-to-formate pathway by reducing the energy barrier toward HCOOH and largely weakening the adsorption of*CO intermediates on the catalyst surface.This study reveals that the unique PdBi bimetallic interface can provide a novel platform to study the reaction mechanism through combining in-situ ATR-SEIRAS and DFT calculations.

关键词： carbon dioxide reduction reaction bimetallic PdBi interface engineering formate in-situ attenuated total reflection surface enhanced infrared absorption spectroscopy(ATR-SEIRAS)

A CRISPR/Cas12a-empowered surface plasmon resonance platform for rapid and specific diagnosis of the Omicron variant of SARS-CoV-2

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National Science Review 2022年第8期9卷 100-109页

作者： Zhi Chen Jingfeng Li Tianzhong Li Taojian Fan Changle Meng Chaozhou Li Jianlong Kang Luxiao Chai Yabin Hao Yuxuan Tang Omar A.Al-Hartomy Swelm Wageh Abdullah G.Al-Sehemi Zhiguang Luo Jiangtian Yu Yonghong Shao Defa Li Shuai Feng William J.Liu Yaqing He Xiaopeng Ma Zhongjian Xie Han Zhang Department of Physics Faculty of Science King Abdulaziz University research Center for Advanced Materials Science (RCAMS) King Khalid University Department of Chemistry College of Science King Khalid University Zhongmin (shenzhen) Intelligent Ecology Co.Ltd Key Laboratory of Optoelectronic Devices and Systems of Ministry of Education and Guangdong Province College of Physics and Optoelectronic Engineering Shenzhen University Department of Laboratory Medicine Shenzhen Children’s Hospital Optoelectronics research Center School of Science Minzu University of China NHC Key Laboratory of Biosafety National Institute for Viral Disease Control and Prevention Chinese Center for Disease Control and Prevention research Unit of Adaptive Evolution and Control of Emerging Viruses Chinese Academy of Medical Sciences institute of Pathogenic Organism Shenzhen Center for Disease Control and Prevention shenzhen Engineering Laboratory of Phosphorene and Optoelectronics Respiratory Department Shenzhen Children’s Hospital institute of Pediatrics Shenzhen Children’s Hospital international Collaborative Laboratory of 2D Materials for Optoelectronics Science and Technology of Ministry of Education 3. shenzhen institute of Translational Medicine 4. Department of Otolaryngology Shenzhen Second People’s Hospital 5. the First Affiliated Hospital 6. Institute of Microscale Optoelectronics Shenzhen University 7. Shenzhen International Institute for Biomedical Research 8. Shenzhen Han’s Tech Limited Company 9. Shenzhen Metasensing Tech Limited Company

The outbreak of the COVID-19 pandemic was partially due to the challenge of identifying asymptomatic and presymptomatic carriers of the virus, and thus highlights a strong motivation for diagnostics with high sensitivity that can be rapidly deployed. On the other hand, several concerning SARS-Co V-2 variants,including Omicron, are required to be identified as soon as the samples are identified as ‘positive’.Unfortunately, a traditional PCR test does not allow their specific identification. Herein, for the first time,we have developed MOPCS(Methodologies of Photonic CRISPR Sensing), which combines an optical sensing technology-surface plasmon resonance(SPR) with the ‘gene scissors’ clustered regularly interspaced short palindromic repeat(CRISPR) technique to achieve both high sensitivity and specificity when it comes to measurement of viral variants. MOPCS is a low-cost, CRISPR/Cas12a-systemempowered SPR gene-detecting platform that can analyze viral RNA, without the need for amplification,within 38 min from sample input to results output, and achieve a limit of detection of 15 fM. MOPCS achieves a highly sensitive analysis of SARS-Co V-2, and mutations appear in variants B.1.617.2(Delta),B.1.1.529(Omicron) and BA.1(a subtype of Omicron). This platform was also used to analyze some recently collected patient samples from a local outbreak in China, identified by the Centers for Disease Control and Prevention. This innovative CRISPR-empowered SPR platform will further contribute to the fast, sensitive and accurate detection of target nucleic acid sequences with single-base mutations.

关键词： surface plasmon resonance CRISPR SARS-CoV-2 Omicron variant