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Phosphoester modified poly(ethylenimine) as efficient and low cytotoxic genevectors

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Science China Chemistry 2011年第2期54卷 351-358页

作者： DU JinZhi TANG LingYan yuan youyong WANG Jun Department of Polymer Science and Engineering CAS Key Laboratory of Soft Matter Chemistry University of Science and Technology of China Hefei 230026 China Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences University of Science and Technology of China Hefei 230027 China

Cyclic phosphoester monomer ethyl ethylene phosphate (EEP) modified poly(ethylenimine) (PEI),denoted as PEI-EEP,was developed for gene *** PEI-EEP polymers were synthesized and their structures were characterized by 1H and 31P NMR *** the PEI-EEP polymers could condense DNA efficiently at N/P ratios higher than 0.5/*** physiochemical characteristics of PEI-EEP/DNA complexes were analyzed by particle size and zeta potential *** particle sizes of complexes were around 160–250 nm,and their zeta potentials were around 30–45 mV at the N/P ratios ranging from 10/1 to 50/*** vitro cell viability and transfection ability were evaluated in HEK293 and HeLa cells using PEI as the *** cytotoxicity of PEI-EEP and PEI-EEP/DNA complexes was lower than that of PEI and its complexes with *** transfection efficiency of PEI-EEP/DNA complexes was correlated to modification degrees with *** the modification of phosphoester to PEI was moderate,the PEI-EEP1/DNA and PEI-EEP2/DNA complexes exhibited comparable or even higher transfection ability than PEI/DNA complex at its optimal N/P ratio in the absence of ***,transfection efficiency of PEI-EEP3 reduced *** importantly,the PEI-EEP exhibited higher transfection efficiency in the presence of 10% serum than that without ***,PEI-EEP polymers may be attractive vectors for non-viral gene therapy.

关键词： gene delivery PEI phosphoester gene vector

Dual drug delivery system with flexible and controllable drug ratios for synergistic chemotherapy

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Science China Chemistry 2021年第6期64卷 1020-1030页

作者： Yalan Tu Rui Zheng Fangzhou Yu Xuan Xiao Maoling Jiang youyong yuan Institutes for Life Sciences School of MedicineSouth China University of TechnologyGuangzhou 510006China National Engineering Research Center for Tissue Restoration and Reconstruction South China University of TechnologyGuangzhou 510006China Key Laboratory of Biomedical Materials and Engineering of the Ministry of Education South China University of TechnologyGuangzhou 510006China Key Laboratory of Biomedical Engineering of Guangdong Province and Innovation Center for Tissue Restoration and Reconstruction South China University of TechnologyGuangzhou 510006China Bioland Laboratory(Guangzhou Regenerative Medicine and Health Guangdong Laboratory) Guangzhou 510005China

Determination of whether multidrug nanocarriers can deliver and release loaded drugs at a predefined synergistic ratio to target cancer cells is *** there are many successful applications for delivery of multiple drugs,most current carriers are unable to achieve coordinated loading and release,leading to a drug release ratio that disagrees with the predefined loading *** this work,a simple dual-drug delivery system with a flexible and controllable drug release ratio was constructed to deliver two anticancer drugs,doxorubicin(DOX)and curcumin(CUR).The drug ratio of DOX and CUR can be easily tuned for an enhanced synergistic effect,and the drugs can be released at predesigned ratios due to synchronous drug activation and nanoparticle *** release at predefined ratios for synergistic anticancer therapy was demonstrated via in vitro and in vivo experiments.

关键词： nanomedicine drug delivery system combination therapy synergistic chemotherapy

Surface charge tunable nanoparticles for TNF-α siRNA oral delivery for treating ulcerative colitis

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Nano Research 2018年第5期11卷 2872-2884页

作者： Shoaib Iqbal Xiaojiao Du Jilong Wang Hongjun Li youyong yuan Jun Wang School of Life Sciences University of Science and Technology of China Hefei 230027 China School of Medicine South China University of Technology Guangzhou 510006 China Institutes for Life Sciences South China University of Technology Guangzhou 510006 China Key Laboratory of Biomedical Materials of Ministry of Education South China University of Technology Guangzhou 510641 Chino National Engineering Research Center for Tissue Restoration and Reconstruction Guangzhou 510006 China Research Institute for Food Nutrition and Human Health Guangzhou 510641 China

Nanopartide （NP） drug delivery systems have been successfully designed and implemented to orally deliver small interfering RNAs （siRNAs） for inflammatory disorders. However, the influence of surface charge on orally administered siRNA nanocarriers has not been investigated. In this study, we prepared structurally related poly（ethylene glycol）-block-poly（lactic-co-glycolic acid）（PEG5K-b-PLGA10K） NPs with the assistance of a synthesized lipid featuring surface amine groups for subsequent charge tuning. NPs were prepared by a double emulsion method, and their surface charge could be tuned and controlled by a succinylation reaction to yield NPs with different surface charges, while maintaining their size and composition. The prepared NPs were termed as aminated NPs （ANPs）, plain NPs （PNPs）, or carboxylated NPs （CNPs） based on their surface charge. All NPs exhibited the desired structural stability and siRNA integrity after enzymatic degradation. In vivo studies showed that ANPs significantly accumulated in inflamed colons, and they were successful in decreasing TNF-α secretion and mRNA expression levels while maintaining colonic histology in a murine model of acute ulcerative colitis （UC）. This study described a methodology to modify the surface charge of siRNA-encapsulating polymeric NPs and highlighted the influence of surface charge on oral delivery of siRNA for localized inflammatory disorders.

关键词： surface charge tumor necrosis factor alpha(TNF-α) small interferingRNA (siRNA) drug delivery polymeric nanoparticles ulcerative colitis

Tumor-Selective Cascade-Amplified Dual-Prodrugs Activation for Synergistic Oxidation-Chemotherapy

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CCS Chemistry 2022年第12期4卷 3878-3888页

作者： Xuan Xiao Qingyu Zong Jisi Li youyong yuan School of Biomedical Sciences and Engineering South China University of TechnologyGuangzhou 511442 National Engineering Research Center for Tissue Restoration and Reconstruction South China University of TechnologyGuangzhou 510006 School of Medicine South China University of TechnologyGuangzhou 510006 Key Laboratory of Biomedical Materials and Engineering of the Ministry of Education South China University of TechnologyGuangzhou 510006 Guangdong Provincial Key Laboratory of Biomedical Engineering South China University of TechnologyGuangzhou 510006

Efficacy of prodrugs in cancer therapy requires selective and efficient drug activation in cancer ***,we report a novel dual-prodrug delivery system with tumor-selective cascade-amplified prodrug activation for synergistic *** cells overexpressing cathepsin B-activatable nearinfrared(NIR)hemicyanine prodrug(CyNH-Citval)were encapsulated by the reactive oxygen species(ROS)-responsive polyprodrug of doxorubicin(DOX)(PTK_(DOX))to obtain PTK_(DOX/Cy).Upon uptake of PTK_(DOX/Cy) by cancer cells and subsequent prodrug CyNH-Citval activation,NIR fluorescence was turned on and toxicity toward mitochondria was restored,thereby elevating intracellular ROS levels,which subsequently activated the polyprodrug PTK_(DOX) to initiate the cascade and amplify ***,these results indicate that enzyme-mediated initiation of drug activation and amplification of cascade ROS ultimately causes selective and efficient prodrug activation in tumors with synergistic oxidation and *** findings provide new insights to inform precise cooperative cancer therapy.

关键词： prodrug cascade drug activation oxidation-chemotherapy cancer therapy drug delivery

Echinacea purpurea-derived homogeneous polysaccharide exerts anti-tumor efficacy via facilitating M1 macrophage polarization

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The Innovation 2023年第2期4卷 68-76,67页

作者： Wenkai Ren Junfeng Ban Yaoyao Xia Fang Zhou Caihong yuan Huanhuan Jia Hailan Huang Mingmin Jiang Minjian Liang Zhaodong Li youyong yuan Yulong Yin Hong Wu State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources Laboratory for Lingnan Modern AgricultureSouth China Agricultural UniversityGuangzhou 510642China Guangdong Technology Research Center for Traditional Chinese Veterinary Medicine and Natural Medicine South China Agricultural UniversityGuangzhou 510642China Guangdong Provincial Key Laboratory of Advanced Drug Delivery Systems Guangdong Pharmaceutical UniversityGuangzhou 510006China Sericulture&Agri-Food Research Institute Guangdong Academy of Agricultural Sciences Key Laboratory of Functional FoodsMinistry of Agriculture and Rural AffairsGuangdong Key Laboratory of Agricultural Products ProcessingGuangzhou 510640China Key Laboratory of Guangdong Laboratory Animals Guangdong Laboratory Animals Monitoring InstituteGuangzhou 510663China School of Biomedical Sciences and Engineering South China University of TechnologyGuangzhou International CampusGuangzhou 511442China Institute of Subtropical Agriculture Chinese Academy of SciencesChangsha 511442China

Echinacea purpurea modulates tumor progression,but the underlying mechanism is poorly *** isolated and purified a novel homogeneous polysaccharide from ***(EPPA),which was shown to be an arabinogalactan with a mean molecular mass(Mr)of 3.8×10^(4)Da and withα-(1→5)-L-Arabinan as the backbone and a-L-Araf-(1→,→6)-b-D-Galp-(1→,and →4)-α-D-GalpA-(1/as the side ***,oral administration of EPPA suppresses tumor progression in vivo and shapes the immune cell profile(e.g.,facilitating M1 macrophages)in tumor micro-environment by single-cell RNA sequencing(scRNA-seq)analysis.

关键词： purpurea macrophage analysis.

Bioorthognal Equipping CAR-T Cells with Hyaluronidase and Checkpoint Blocking Antibody for Enhanced Solid Tumor Immunotherapy

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Bioorthognal Equipping CAR-T Cells with Hyaluronidase and Ch...

Heme oxygenase 1-mediated ferroptosis in Kupffer cells initiates liver injury during heat stroke

第十四届全国免疫学学术大会

作者： Yangyang Zhao Yansong Dong Shuhan Yang youyong yuan Zhexiong Lian South China University of Technology

Adoptive cellular therapy utilizing Chimeric antigen receptor-redirected T(CAR-T) cells has shown striking therapeutic effects on hematological malignancies. In contrast, the efficacy of treating solid tumors with CAR-T cell therapies is still poor, which is largely due to inefficient penetration into solid tumors and immunosuppressive tumor microenvironment. Herein, we engineered hyaluronidase(HAase) and the checkpoint blocking antibody α-PDL1 on the surface of CAR-T cells via highly efficient and biocompatible bioorthogonal click chemistry to improve the therapeutic effects of CAR-T cells on solid tumors. The modified HAase degrades hyaluronic acid and destroys the tumor extracellular matrix, allowing CAR-T cells penetrate deeply into solid tumors, as evidenced by in vitro infiltration experiments and in vivo biodistribution studies. In addition, in vitro cytotoxicity studies showed stronger antitumor activity of α-PDL1-decorated CAR-T cells than traditional CAR-T cells. Importantly, HAase-and α-PDL1-engineered CAR-T cells showed better therapeutic efficacy on A20 solid tumors, and did not cause significant systemic toxicity. In this work, we provided a simple, efficient, and biologically safe chemical strategy to engineer traditional CAR-T cells for enhanced therapeutic efficacy on solid tumors, which can be extended to other adoptive cellular immunotherapies and holds great potential for clinical application.

关键词： Bioorthogonal reaction Chimeric antigen receptor T cell Immunotherapy Solid tumor

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Acta Pharmaceutica Sinica B 2024年第9期14卷 3983-4000页

作者： Ru Li Riqing Wei Chenxin Liu Keying Zhang Sixiao He Zhifeng Liu Junhao Huang youyong Tang Qiyuan An Ligen Lin Lishe Gan Liying Zhao Xiaoming Zou Fudi Wang yuan Ping Qiang Ma The Seventh Affiliated Hospital Southern Medical UniversityFoshan 528244China Department of Biopharmaceutics School of Laboratory Medicine and BiotechnologySouthern Medical UniversityGuangzhou 510000China Medical Critical Care Medicine General Hospital of Southern Theatre Command of PLAGuangzhou 510000China Guangdong Branch Center National Clinical Research Center for Geriatric Diseases(Chinese PLA General Hospital)Guangzhou 510000China State Key Laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical SciencesUniversity of MacaoAvenida da UniversidadeTaip1Macao 999078China School of Pharmaceutical Sciences Zhejiang Chinese Medical UniversityHangzhou 311402China Department of General Surgery Nanfang Hospitalthe First School of Clinical MedicineSouthern Medical UniversityGuangzhou 510000China The Fourth Affiliated Hospital the First Affiliated HospitalSchool of Public HealthInstitute of Translational MedicineCancer CenterState Key Laboratory of Experimental HematologyZhejiang University School of MedicineHangzhou 310000China The First Affiliated Hospital the Second Affiliated HospitalBasic Medical SciencesSchool of Public HealthHengyang Medical SchoolUniversity of South ChinaHengyang 421200China College of Pharmaceutical Sciences Zhejiang UniversityHangzhou 310000China Liangzhu Laboratory Zhejiang University Medical CenterHangzhou 310000China Guangdong Provincial Key Laboratory of Immune Regulation and Immunotherapy School of Laboratory Medicine and BiotechnologySouthern Medical UniversityGuangzhou 510000China

With the escalating prevalence of global heat waves,heat stroke has become a prominent health concern,leading to substantial liver *** other forms of liver injury,heat strokeinduced damage is characterized by heat cytotoxicity and heightened inflammation,directly contributing to elevated mortality *** clinical assessments have identified elevated bilirubin levels as indicative of Kupffer cell dysfunction,their specific correlation with heat stroke liver injury remains *** hypothesis proposes the involvement of Kupffer cell ferroptosis during heat stroke,initiating IL-1bmediated *** single-cell RNA sequencing of murine macrophages,a distinct and highly susceptible Kupffer cell subtype,Clec4Ft/CD206t,emerged,with heme oxygenase 1(HMOX-1)playing a pivotal ***,heat-induced HMOX-1,regulated by early growth response factor 1,mediated ferroptosis in Kupffer cells,specifically in the Clec4F t/CD206 t subtype(KC2),activating phosphatidylinositol 4-kinase beta and promoting PI4P *** cascade triggered NLRP3 inflammasome activation and maturation of *** findings underscore the critical role of targeted therapy against HMOX-1 in ferroptosis within Kupffer cells,particularly in Clec4F t/CD206 t *** an approach has the potential to mitigate inflammation and alleviate acute liver injury in the context of heat stroke,offering a promising avenue for future therapeutic interventions.

关键词： Heat stroke Liver injury Kupffer cells Ferroptosis Heme oxygenase 1 Phosphatidylinositol 4-kinase beta NLRP3 Early growth response factor 1

The origin and evolution of Earth's nitrogen

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National Science Review 2024年第6期11卷 56-75页

作者： yuan Li State Key Laboratory of Isotope Geochemistry Guangzhou Institute of GeochemistryChinese Academy of Sciences Bayerisches Geoinstitut Universit?t Bayreuth

Nitrogen is a vital element for life on Earth. Its cycling between the surface(atmosphere + crust) and the mantle has a profound influence on the atmosphere and climate. However, our understanding of the origin and evolution of Earth's nitrogen is still incomplete. This review presents an overview of the current understanding of Earth's nitrogen budget and the isotope composition of different reservoirs, laboratory constraints on deep nitrogen geochemistry, and our understanding of the origin of Earth's nitrogen and the deep nitrogen cycle through plate subduction and volcanism. The Earth may have acquired its nitrogen heterogeneously during the main accretion phase, initially from reduced, enstatite-chondrite-like impactors,and subsequently from increasingly oxidized impactors and minimal CI-chondrite-like materials. Like Earth's surface, the mantle and core are also significant nitrogen reservoirs. The nitrogen abundance and isotope composition of these three reservoirs may have been fundamentally established during the main accretion phase and have been insignificantly modified afterwards by the deep nitrogen cycle, although there is a net nitrogen ingassing into Earth's mantle in modern subduction zones. However, it is estimated that the early atmosphere of Earth may have contained ～1.4 times the present-day atmospheric nitrogen(PAN),with ～0.4 PAN being sequestered into the crust via biotic nitrogen fixation. In order to gain a better understanding of the origin and evolution of Earth's nitrogen, directions for future research are suggested.

关键词： nitrogen isotopes silicate Earth atmosphere magma ocean

Robustness of the octupole collectivity in 144Ba within the cranking covariant density functional theory in 3D lattice

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Nuclear Science and Techniques 2024年第8期35卷 124-131页

作者： Ze‑Kai Li yuan‑yuan Wang Mathematics and Physics Department North China Electric Power UniversityBeijing 102206China Hebei Key Laboratory of Physics and Energy Technology North China Electric Power UniversityBaoding 071000China

The octupole deformation and collectivity in octupole double-magic nucleus 144Ba are investigated using the Cranking covariant density functional theory in a three-dimensional lattice *** reduced B(E3)transition probability is implemented for the first time in semiclassical approximation based on the microscopically calculated electric octupole *** available data,including the I-ωrelation and electric transitional probabilities B(E2)and B(E3)are well ***,it is shown that the ground state of 144Ba exhibits axial octupole and quadrupole deformations that persist up to high spins(I≈24h).

关键词： Octupole collectivity Cranking covariant density functional theory Rotational spectrum Electric transitional probabilities