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Chemical Research in Chinese Universities 2022年第2期38卷 562-571页

作者： WU Liting XIN Yujia GUO Zhaoyang GAO Wei ZHU Yanpeng WANG Yinsong RAN Ruixue YANG Xiaoying Tianjin Key Laboratory on Technologies Enabling Development of Clinical therapeutics and Diagnostics(Theranostics) School of PharmacyTianjin Medical UniversityTianjin 300070P.R.China

Combining photothermal therapy and radiotherapy(PTT-RT) with reducing tumor hypoxia acts as an important antitumor modality. However, it is a great challenge to realize photothermal therapy, radiotherapy and exogenous oxygen supply in one nanosystem. To realize a combination of the three functions, we fabricated a red blood cell membrane(RBCm)-camouflaged, red blood cell content(RBCc) and the copper sulfide(CuS) co-loaded dendritic large pore mesoporous silica nanoparticle(DLMSN/CuS/RBCc/ RBCm). The cell membrane coating endowed the nanoparticles with good stability in the physiological environment, and CuS allowed the nanoparticle exhibiting good photothermal and radiosensitization properties. RBCc loaded nanoparticle DLMSN/CuS/RBCc enhanced superior anti-tumor effect than DLMSN/CuS during combined PTT-RT therapy because the introduction of RBCc increased the exogenous oxygen supply. The in vitro study further demonstrated that the combination of photothermal therapy and radiotherapy induced superior antitumor efficacy than single therapy. Our work thus presents a unique multifunctional nanoscale platform favorable for combined PTT and RT.

关键词： Dendritic large pore mesoporous silica nanoparticle Photothermal therapy Radiosensitization Red blood cell membrane Oxygen carrying

miR-126-5p affects the chemosensitivity of colorectal cancer cells by regulating SPRED1, ERK1/2 pathway and apoptosis

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Genes & Diseases 2023年第3期10卷 675-678页

作者： Mingshi Xu Gang Zhang Xiaofan Gu Fangqin Zhao Zhongmin Yang Xiongwen Zhang Shanghai Engineering Research Center of Molecular therapeutics and New Drug Development School of Chemistry and Molecular EngineeringEast China Normal UniversityShanghai 200241China

Chemoresistance is still one of the main obstacles to treat colorectal cancer(CRC).Substantial studies on biomarkers related to chemoresistance have emerged in recent *** microRNAs(miRNA)have been reported to involved in drug resistance and CRC.1 MiR-126-5p participates in malignant behaviors of numerous cancers.2,3 However,it is not known if miR-126-5p participates in multidrug resistance in ***,the impact of miR-126-5p on drug resistance of CRC and its drug resistance mechanism have not been reported.

关键词： colorectal miR cancer

Fish-on-Chips:unveiling neural processing of chemicals in small animals through precise fluidic control

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Neural Regeneration Research 2024年第11期19卷 2351-2353页

作者： Samuel K.H.Sy Ho Ko Division of Neurology Department of Medicine and TherapeuticsFaculty of MedicineThe Chinese University of Hong KongShatinNew TerritoriesHong Kong Special Administrative RegionChina Li Ka Shing Institute of Health Sciences Faculty of MedicineThe Chinese University of Hong KongShatinNew TerritoriesHong Kong Special Administrative RegionChina Department of Electrical and Electronic Engineering Faculty of EngineeringThe University of Hong KongPok Fu LamHong Kong IslandHong Kong Special Administrative RegionChina Advanced Biomedical Instrumentation Center Hong Kong Science ParkPak Shek KokNew TerritoriesHong Kong Special Administrative RegionChina Margaret K.L.Cheung Research Center for Management of Parkinsonism Faculty of MedicineThe Chinese University of Hong KongShatinNew TerritoriesHong Kong Special Administrative RegionChina Lau Tat-chuen Research Center of Brain Degenerative Diseases in Chinese Faculty of MedicineThe Chinese University of Hong KongShatinNew TerritoriesHong Kong Special Administrative RegionChina Gerald Choa Neuroscience Institute The Chinese University of Hong KongShatinNew TerritoriesHong Kong Special Administrative RegionChina

Precise chemical cue presentation alongside advanced brainwide imaging techniques is important to the study of chemosensory processing in ***,the dynamic nature of chemical-carrying media,such as water or air,poses a significant challenge for delivering highly-controlled chemical flow to an animal ***,contact-based cue manipulation and delivery easily shift the position of the animal subject,which is often undesirable for high-quality brain ***,more advanced interfacing tools that align with the diverse range of body part sizes of an animal,ranging from micrometer-scale neurons to meter-long limbs,are much *** is particularly crucial when dealing with dimensions that are beyond the reach of conventional experimental tools.

关键词： dealing precise sizes

Monitoring the in vivo siRNA release from lipid nanoparticles based on the fluorescence resonance energy transfer principle

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Asian Journal of Pharmaceutical Sciences 2023年第1期18卷 72-85页

作者： Lei Sun Jinfang Zhang Jing-e Zhou JingWang Zhehao Wang Shenggen Luo Yeying Wang Shulei Zhu Fan Yang Jie Tang Wei Lu Yiting Wang Lei Yu Zhiqiang Yan Institute of Biomedical Engineering and Technology Shanghai Engineering Research Center of Molecular Therapeutics and New Drug DevelopmentSchool of Chemistry and Molecular EngineeringEast China Normal UniversityShanghai 200062China Shanghai Engineering Research Center of Molecular therapeutics and New Drug Development School of Chemistry and Molecular EngineeringEast China Normal UniversityShanghai 200062China

The siRNA-loaded lipid nanoparticles have attracted much attention due to its significant gene silencing effect and successful ***,the in vivo distribution and release of siRNA still cannot be effectively *** this study,based on the fluorescence resonance energy transfer(FRET)principle,a fluorescence dye Cy5-modified survivin siRNA was conjugated to nanogolds(Au-DR-siRNA),which were then wrapped with lipid nanoparticles(LNPs)for monitoring the release behaviour of siRNA in *** results showed that once Au-DR-siRNA was released from the LNPs and cleaved by the Dicer enzyme to produce free siRNA in cells,the fluorescence of Cy5 would change from quenched state to activated state,showing the location and time of siRNA ***,the LNPs showed a significant antitumor effect by silencing the survivin gene and a CT imaging function superior to iohexol by ***,this work provided not only an effective method for monitoring the pharmacokinetic behaviour of LNP-based siRNA,but also a siRNA delivery system for treating and diagnosing tumors.

关键词： Survivin siRNA Lipid nanoparticles In vivo release Nanogolds Fluorescence resonance energy transfer

Engineered AAV13 variants with enhanced transduction and confined spread

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Zoological Research 2024年第4期45卷 781-790页

作者： Neng-Song Luo Yu-Xiang Cai Zeng-Peng Han Xiao-Kai Sui Wen-Jia Yuan Zi-Lian Zhang Hao-Dong Guo Jie Wang Kun-Zhang Lin Fu-Qiang Xu Wuhan National Laboratory for Optoelectronics Huazhong University of Science and TechnologyWuhanHubei 430074China Shenzhen Key Laboratory of Viral Vectors for Biomedicine Shenzhen-Hong Kong Institute of Brain ScienceShenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhenGuangdong 518055China Key Laboratory of Magnetic Resonance in Biological Systems State Key Laboratory of Magnetic Resonance and Atomic and Molecular PhysicsNational Center for Magnetic Resonance in WuhanInnovation Academy for Precision Measurement Science and TechnologyChinese Academy of SciencesWuhanHubei 430071China Key Laboratory of Quality Control Technology for Virus-Based therapeutics Guangdong Provincial Medical Products AdministrationNMPA Key Laboratory for Research and Evaluation of Viral Vector Technology in Cell and Gene Therapy Medicinal ProductsBrain Cognition and Brain Disease InstituteShenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhenGuangdong 518055China University of Chinese Academy of Sciences Beijing 100049China Zhongnan Hospital Wuhan UniversityWuhanHubei 430072China Brain Case Biotechnology Co. Ltd.ShenzhenGuangdong 518107China College of Life Sciences Wuhan UniversityWuhanHubei 430072China Center for Excellence in Brain Science and Intelligence Technology Chinese Academy of SciencesShanghai 200031China

Precise targeting of specific regions within the central nervous system(CNS)is crucial for both scientific research and gene therapy in the context of brain ***-associated virus 13(AAV13)is known for its restricted diffusion range within the CNS,making it an ideal choice for precise labeling and administration within small brain ***,AAV13 mediates relatively low expression of target ***,we introduced specifically engineered modifications to the AAV13 capsid protein to enhance its transduction *** first constructed AAV13-YF by mutating tyrosine to phenylalanine on the surface of the AAV13 *** then inserted the 7m8 peptide,known to enhance cell transduction,into positions 587/588 and 585/586 of the AAV13 capsid,resulting in two distinct variants named AAV13-587-7m8 and AAV13-585-7m8,*** found that AAV13-YF exhibited superior in vitro infectivity in HEK293T cells compared to AAV13,while AAV13-587-7m8 and AAV13-585-7m8 showed enhanced CNS infection capabilities in C57BL/6 mice,with AAV13-587-7m8 infection retaining a limited spread *** modified AAV13 variants hold promising potential for applications in gene therapy and neuroscience research.

关键词： Adeno-associated virus 13 AAV13-YF AAV13-587-7m8 AAV13-585-7m8 transduction efficiency

Toll-like receptor agonists shape the immune responses to a mannose receptor-targeted cancer vaccine

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Cellular & Molecular Immunology 2015年第6期12卷 719-728页

作者： Li-Zhen He Jeffrey Weidlick Crystal Sisson Henry C Marsh Tibor Keler Celldex therapeutics Inc. Hampton N J USA and Celldex therapeutics Inc. Needham MA USA

Previous studies have documented that selective delivery of protein antigens to cells expressing mannose receptor （MR） can lead to enhanced immune responses. We postulated that agents that influenced the MR expression level, and the activation and migration status of MR-expressing antigen presenting cells, would modulate immune responses to MR-targeted vaccines. To address this question, we investigated the effect of clinically used adjuvants in human MR transgenic （hMR-Tg） mice immunized with an MR-targeting cancer vaccine composed of the human anti-MR monoclonal antibody B 11 fused with the oncofetal protein, human chorionic gonadotropin beta chain （hCGβ）, and referred to as B 11-hCGβ. We found that humoral responses to low doses of B11-hCGβ could be enhanced by prior administration of GM-CSF, which upregulated MR expression in vivo. However, co-administration of the Toll-like receptor （TLR） agonists, poly-ICLC and/or CpG with B11-hCGβ was required to elicit Thl immunity, as measured by antigen-specific T-cell production of IFN-γ. The TLR agonists were shown to increase the number of vaccine-containing cells in the draining lymph nodes of immunized hMR-Tg mice. In particular, with B11-hCGβand poly-ICLC, a dramatic increase in vaccine-positive cells was observed in the T-ceU areas of the lymph nodes, compared to the vaccine alone or combined with GM-CSF. Importantly, the absence of the TLR agonists during the priming immunization led to antigen-specific tolerance. Therefore, this study provides insight into the mechanisms by which adjuvants can augment immune responses to B11-hCGβ and have implications for the rationale design of clinical studies combining MR-targeted vaccination with TLR agonists.

关键词： GM-CSF hCGβ mannose receptor Toll-like receptor agonists

The role of MT1-MMP in the progression and metastasis of osteosarcoma

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Journal of Cancer Metastasis and Treatment 2022年第1期8卷 564-578页

作者： Hannah L.M.Spencer Steven D.Shnyder Paul M.Loadman Robert A.Falconer Institute of Cancer therapeutics Faculty of Life SciencesUniversity of BradfordBradford BD71DPUK

The dysregulation of Membrane-type 1 matrix metalloproteinase(MT1-MMP)has been extensively studied in numerous cancer types,and plays key roles in angiogenesis,cancer progression,and ***1-MMP is a predictor of poor prognosis in osteosarcoma(OS),yet the molecular mechanisms of disease progression are *** review provides a summary of the literature relating to the gene and protein expression of MT1-MMP(MMP-14)in OS clinical samples,evaluates the expression in cell lines and experimental models,and analyses its potential role in the progression and metastasis of *** addition,the therapeutic potential of MT1-MMP as a drug target has been *** to the biological complexity of MMPs,inhibition has proven to be ***,exploiting the expression and proteolytic capacity of MT1-MMP could open new avenues in the search for novel,safer and selective drugs for use in OS.

关键词： Matrix metalloproteinase membrane-type osteosarcoma MT1-MMP

ABC efflux transporters at blood-central nervous system barriers and their implications for treating spinal cord disorders

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Neural Regeneration Research 2020年第7期15卷 1235-1242页

作者： Liam M. Koehn Department of Pharmacology and therapeutics the University of Melbourne

The barriers present in the interfaces between the blood and the central nervous system form a major hurdle for the pharmacological treatment of central nervous system injuries and *** family of ATP-binding cassette(ABC)transporters has been widely studied regarding efflux of medications at blood-central nervous system *** efflux transporters include P-glycoprotein(abcb1),‘breast cancer resistance protein'(abcg2)and the various‘multidrug resistance-associated proteins'(abccs).Understanding which efflux transporters are present at the blood-spinal cord,blood-cerebrospinal fluid and cerebrospinal fluid-spinal cord barriers is necessary to determine their involvement in limiting drug transfer from blood to the spinal cord *** developments in the blood-brain barrier field have shown that barrier systems are dynamic and the profile of barrier defenses can alter due to conditions such as age,disease and environmental *** means that a true understanding of ABC efflux transporter expression and localization should not be one static value but instead a range that represents the complex patient subpopulations that *** the present review,the blood-central nervous system barrier literature is discussed with a focus on the impact of ABC efflux transporters on:(i)protecting the spinal cord from adverse effects of systemically directed drugs,and(ii)limiting centrally directed drugs from accessing their active sites within the spinal cord.

关键词： ABC transporters ATP-binding cassette BCRP blood-brain barrier blood-spinal cord barrier efflux MRP P-glycoprotein PGP spinal cord injury

Editorial:minor stroke is not minor

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Stroke & Vascular Neurology 2023年第3期8卷 175-177页

作者： Xinyi Leng David Wang Medicine&therapeutics The Chinese University of Hong KongHong KongChina Barrow Neurological Institute Petznick Stroke Center PhoenixAZUSA

Defining minor stroke can be complicated.A minor stroke can be called a mini or small *** is often defined by the severity of neurological deficit,size of ischaemic lesion(s)on neuroimaging,and level of *** definition... 详细信息

关键词： minor severity transient

Synthesis of Piperazic Acid-Containing Cyclodepsipeptide Core of Verucopeptin

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Chinese Journal of Chemistry 2023年第17期41卷 2077-2081页

作者： Yuanjun Sun Wenhao Tang Mei Wang Huxin Ni Ya-Qiu Long Laboratory of Medicinal Chemical Biology College of Pharmaceutical SciencesJiangsu Province Engineering Research Centerof Precision Diagnostics and Therapeutics DevelopmentSoochow UniversitySuzhouJiangsu 215123China

Comprehensive SummaryChemically,N1 nitrogen of piperazic acid is more nucleophilic than N2 nitrogen,but amide bonds predominantly formed at N2 nitrogen are prevalent in piperazic acid-containing natural products,with only one exception of *** two orthogonal protecting groups of nitrogen are often employed to realize selective coupling of N2 nitrogen,resulting in increased synthetic steps and low synthetic ***,we develop selective deprotection of N2-Cbz from the N1,N2-diCbz-piperazic acid-containing peptide to form the N2 amide exclusively,avoiding the tedious orthogonal protection strategy which is commonly applied when the easily-accessible N1,N2-diCbz-piperazic acid is used as the synthetic *** employ this selective-deprotection strategy to achieve an efficient synthesis of piperazic acid-containing cyclodepsipeptide core of verucopeptin with an overall yield of 21%from commercially/readily available building blocks.

关键词： Natural products Piperazic acid Verucopeptin Total synthesis Regioselectivity