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Organelle-inspired supramolecular nanomedicine to precisely abolish liver tumor growth and metastasis

Bioactive Materials 2022年第3期7卷 120-133页

作者： Jie Zhan Yuhan Wang Shaodan Ma Qin Qin Ling Wang Yanbin Cai zhimou yang Shunde Hospital Southern Medical UniversityThe First People’s Hospital of ShundeFoshan528300China Guangdong Provincial Key Laboratory of New Drug Screening School of Pharmaceutical SciencesSouthern Medical UniversityGuangzhou510515China Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering Southern Medical UniversityGuangzhou510515China State Key Laboratory of Medicinal Chemical Biology College of Life SciencesKey Laboratory of Bioactive MaterialsMinistry of EducationCollaborative Innovation Center of Chemical Science and EngineeringAnd National Institute of Functional MaterialsNankai UniversityTianjin300071China Guangdong Provincial Biomedical Engineering Technology Research Center for Cardiovascular Disease Department of Cardiology and Laboratory of Heart CenterZhujiang HospitalSouthern Medical UniversityGuangzhou510280China

Organelles are responsible for the efficient storage and transport of substances in living systems.A myriad of extracellular vesicles(EVs)acts as a bridge to exchange signaling molecules in cell-cell communication,and the highly dynamic tubulins and actins contribute to efficient intracellular substance transport.The inexhaustible cues of natural cargo delivery by organelles inspire researchers to explore the construction of biomimetic architectures for“smart”delivery carriers.Herein,we report a 10-hydroxycamptothecin(HCPT)-peptide conjugate HpYss that simulates the artificial EV-to-filament transformation process for precise liver cancer therapy.Under the sequential stimulus of extracellular alkaline phosphatase(ALP)and intracellular glutathione(GSH),HpYss proceeds via tandem self-assembly with a morphological transformation from nanoparticles to nanofibers.The experimental phase diagram elucidates the influence of ALP and GSH contents on the self-assembled nanostructures.In addition,the dynamic transformation of organelle-mimetic architectures that are formed by HpYss in HepG2 cells enables the efficient delivery of the anticancer drug HCPT to the nucleus,and the size-shape change from extracellular nanoparticles(50-100 nm)to intracellular nanofibers(4-9 nm)is verified to be of key importance for nuclear delivery.Nuclear targeting of HpYss amplifies apoptosis,thus significantly enhancing the inhibitory effect of HCPT(>10-fold)to HepG2 cells.Benefitting from the spatiotemporally controlled nanostructures,HpYss exhibited deep penetration,enhanced accumulation,and long-term retention in multicellular spheroid and xenograft models,potently abolishing liver tumor growth and preventing lung metastasis.We envision that our organelle-mimicking delivery strategy provides a novel paradigm for designing nanomedicine to cancer therapy.

关键词： Self-assembly Organelle-mimicking Nuclear delivery Dynamic cascade process Cancer therapy

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Enzyme-instructed and mitochondria-targeting peptide self-assembly to efficiently induce immunogenic cell death

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Acta Pharmaceutica Sinica B 2022年第6期12卷 2740-2750页

作者： Debin Zheng Jingfei Liu Limin Xie Yuhan Wang Yinghao Ding Rong Peng Min Cui Ling Wang Yongjie Zhang Chunqiu Zhang zhimou yang Key Laboratory of Bioactive Materials Ministry of EducationState Key Laboratory of Medicinal Chemical BiologyCollege of Life SciencesCollaborative Innovation Center of Chemical Science and EngineeringNational Institute of Functional MaterialsNankai UniversityTianjin 300071China College of Pharmacy Nankai UniversityTianjin 300071China Department of Human Anatomy Nanjing Medical UniversityNanjing 211166China

Immunogenic cell death(ICD) plays a major role in cancer immunotherapy by stimulating specific T cell responses and restoring the antitumor immune system.However,effective type Ⅱ ICD inducers without biotoxicity are still very limited.Herein,a tentative drug-or photo sensitizer-free strategy was developed by employing enzymatic self-assembly of the peptide F-pY-T to induce mitochondrial oxidative stress in cancer cells.Upon dephosphorylation catalyzed by alkaline phosphatase overexpressed on cancer cells,the peptide F-pY-T self-assembled to form nanoparticles,which were subsequently internalized.These affected the morphology of mitochondria and induced serious reactive oxygen species production,causing the ICD characterized by the release of danger-associated molecular patterns(DAMPs).DAMPs enhanced specific immune responses by promoting the maturation of DCs and the intratumoral infiltration of tumor-specific T cells to eradicate tumor cells.The dramatic immunotherapeutic capacity could be enhanced further by combination therapy of F-pY-T and anti-PD-L1 agents without visible biotoxicity in the main organs.Thus,our results revealed an alternative strategy to induce efficient ICD by physically promoting mitochondrial oxidative stress.

关键词： Immunogenic cell death Self-assembly Mitochondria targeting Enzyme

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Seamless and early gap healing of osteochondral defects by autologous mosaicplasty combined with bioactive supramolecular nanofiber-enabled gelatin methacryloyl(BSN-GelMA)hydrogel

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Bioactive Materials 2023年第1期19卷 88-102页

作者： Hongwei Wu Yuna Shang Wei Sun Xinyi Ouyang Wenyan Zhou Jieji Lu Shuhui yang Wei Wei Xudong Yao g Xiaozhao Wang Xianzhu Zhang Yishan Chen Qiulin He zhimou yang Hongwei Ouyang Dr.Li Dak Sum&Yip Yio Chin Center for Stem Cells and Regenerative Medicine and Department of Orthopedic Surgery of the Second Affiliated HospitalZhejiang University School of MedicineHangzhouChina Department of Sports Medicine Zhejiang University School of MedicineHangzhouChina Zhejiang University-University of Edinburgh Institute Zhejiang University School of Medicineand Key Laboratory of Tissue Engineering and Regenerative Medicine of Zhejiang ProvinceZhejiang University School of MedicineHangzhouChina China Orthopedic Regenerative Medicine Group(CORMed) HangzhouChina College of Chemistry Tianjin Normal UniversityTianjin300387PR China Faculty of Science The University of MelbourneParkvilleVIC3010Australia International Institutes of Medicine The 4th Affiliated Hospital of Zhejiang University School of MedicineYiwuZhejiangChina Key Laboratory of Bioactive Materials Ministry of EducationState Key Laboratory of Medicinal Chemical BiologyCollege of Life SciencesCollaborative Innovation Center of Chemical Science and Engineeringand National Institute of Functional MaterialsNankai UniversityTianjin300071China

Autologous mosaicplasty is a common approach used to treat osteochondral defects in clinical practice.Gap integration between host and transplanted plugs requires bone tissue reservation and hyaline cartilage regeneration without uneven surface,graft necrosis and sclerosis.However,poor gap integration is a serious concern,which eventually leads to deterioration of joint function.To deal with such complications,this study has developed a strategy to effectively enhance integration of the gap region following mosaicplasty by applying injectable bioactive supramolecular nanofiber-enabled gelatin methacryloyl(GelMA)hydrogel(BSN-GelMA).A rabbit osteochondral defect model demonstrated that BSN-GelMA achieved seamless osteochondral healing in the gap region between plugs of osteochondral defects following mosaicplasty,as early as six weeks.Moreover,the International Cartilage Repair Society score,histology score,glycosaminoglycan content,subchondral bone volume,and collagen II expression were observed to be the highest in the gap region of BSN-GelMA treated group.This improved outcome was due to bio-interactive materials,which acted as tissue fillers to bridge the gap,prevent cartilage degeneration,and promote graft survival and migration of bone marrow mesenchymal stem cells by releasing bioactive supramolecular nanofibers from the GelMA hydrogel.This study provides a powerful and applicable approach to improve gap integration after autologous mosaicplasty.It is also a promising off-the-shelf bioactive material for cell-free in situ tissue regeneration.

关键词： Mosaicplasty Osteochondral integration Bioactive supramolecular nanofiber GelMA hydrogel Tissue engineering

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The protective effects of a D-tetra-peptide hydrogel adjuvant vaccine against H7N9 influenza virus in mice

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Chinese Chemical Letters 2023年第1期34卷 211-214页

作者： Keda Chen Xiaoxin Wu Qingjing Wang Ying Wang Haiyan Zhang Shuai Zhao Chaonan Li Zhiwen Hu zhimou yang Lanjuan Li Shulan International Medical College Zhejiang Shuren UniversityHangzhou 310015China State Key Laboratory for Diagnosis and Treatment of Infectious Diseases Collaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesNational Clinical Research Center for Infectious DiseasesThe First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China Zhejiang Shuren College Zhejiang Chinese Medical UniversityHangzhou 310053China State Key Laboratory of Medicinal Chemical Biology Key Laboratory of Bioactive MaterialsMinistry of EducationCollege of Life SciencesSynergetic Innovation Center of Chemical Science and Engineeringand National Institute of Functional MaterialsNankai UniversityTianjin 300071China Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy Cancer InstituteXuzhou Medical UniversityXuzhou 221004China

Repeated waves of influenza virus H7N9 epidemics after 2013 have caused severe influenza in humans,with mortality reaching approximately 40%–50%.To prevent possible pandemics,the development of highly effective vaccines against influenza virus H7N9 is highly desired.In the present study,by taking advantage of the D-tetra-peptide adjuvant(G^(D)F^(D)F^(D)Y),we reported a simple method to prepare H7N9 vaccines.Naproxen(Npx),with good anti inflammatory and broad anti-viral effects,was employed as an N-terminal capping group to construct a hydrogel precursor,Npx-G^(D)F^(D)F^(D)Y.The hydrogel adjuvant was prepared using a routine heating cooling protocol and the final vaccine was ready after mixing with the split A/Zhejiang/DTID-ZJU01/2013(H7N9)antigen by vortexing.Compared with the traditional Al(OH)_(3) adjuvant vaccine and the split vaccine,our hydrogel adjuvant vaccine showed the best preventive effects against H7N9 infection.A mechanistic study illustrated that higher antibody responses and variations in cytokine expression might account for its increased protective effects.Our strategy demonstrated the advantages of a peptide hydrogel adjuvant in the application of vaccines against H7N9 and demonstrated its potential application in vaccines against emerging threats from other viruses.

关键词： H7N9 influenza virus Hydrogel Adjuvant Vaccine Preventative effects

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Selective nano-buckling improves the performance of graphene logic transistors

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National Science Review 2024年第2期11卷 95-96页

作者： Tong yang Ming yang Department of Applied Physics The Hong Kong Polytechnic University Research Centre for Nanoscience and Nanotechnology The Hong Kong Polytechnic University

The massive integration of silicon-based transistors into modern electronic devices greatly increases power consumption and heat generation/dissipation[1]. In this concern, transistors based on atomically-thin graphene that exhibit high electric and thermoelectric conductivities with negligible contact resistance,

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Deep Insight of Design,Mechanism,and Cancer Theranostic Strategy of Nanozymes

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Nano-Micro Letters 2024年第2期16卷 165-217页

作者： Lu yang Shuming Dong Shili Gai Dan yang He Ding Lili Feng Guixin yang Ziaur Rehman Piaoping yang Key Laboratory of Superlight Materials and Surface Technology Ministry of EducationCollege of Materials Science and Chemical EngineeringHarbin Engineering UniversityHarbin 150001People’s Republic of China Yantai Research Institute Harbin Engineering UniversityYantai 264000People’s Republic of China Key Laboratory of Green Chemical Engineering and Technology of Heilongjiang Province College of Material Science and Chemical EngineeringHarbin University of Science and TechnologyHarbin 150040People’s Republic of China Department of Chemistry Quaid-i-Azam UniversityIslamabad 45320Pakistan

Since the discovery of enzyme-like activity of Fe3O4 nanoparticles in 2007,nanozymes are becoming the promising substitutes for natural enzymes due to their advantages of high catalytic activity,low cost,mild reaction conditions,good stability,and suitable for large-scale production.Recently,with the cross fusion of nanomedicine and nanocatalysis,nanozyme-based theranostic strategies attract great attention,since the enzymatic reactions can be triggered in the tumor microenvironment to achieve good curative effect with substrate specificity and low side effects.Thus,various nanozymes have been developed and used for tumor therapy.In this review,more than 270 research articles are discussed systematically to present progress in the past five years.First,the discovery and development of nanozymes are summarized.Second,classification and catalytic mechanism of nanozymes are discussed.Third,activity prediction and rational design of nanozymes are focused by highlighting the methods of density functional theory,machine learning,biomimetic and chemical design.Then,synergistic theranostic strategy of nanozymes are introduced.Finally,current challenges and future prospects of nanozymes used for tumor theranostic are outlined,including selectivity,biosafety,repeatability and stability,in-depth catalytic mechanism,predicting and evaluating activities.

关键词： Nanozymes Classification Prediction and design Catalytic mechanism Tumor theranostics

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Fresh-Keeping Decision and Coordination of Fresh Agricultural Product Supply Chain Considering Carbon Cap-and-Trade under Different Dominance

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Journal of Systems Science and Systems Engineering 2024年第1期33卷 30-51页

作者： yang yang Guanxin Yao China Institute for Agricultural Equipment Industrial Development Jiangsu UniversityZhenjiang212013China Jiangsu Modern Logistics Research Base Yangzhou UniversityYangzhou225009China

In the context of low carbon,this paper discussed the impact of the carbon cap-and-trade policy on the fresh-keeping decision-making of two-echelon fresh agricultural product supply chains under different dominance,and designed cost-sharing contracts to coordinate the supply chain of fresh agricultural products dominated by suppliers and retailers respectively.The results showed that:dominance has no effect on the fresh-keeping decision and total revenue of fresh agricultural product supply chain,but it affects the internal income distribution,and dominance does not always bring more benefits;the implementation of carbon cap-and-trade reduces the fresh-keeping decision-making of fresh agricultural products supply chain and reduces the free-rider income of followers;the role of higher carbon trading price is twofold,which not only brings about the speculation of leading enterprises,but also promotes the application of low-carbon technologies;consumers’high preference for freshness,low-cost and high-efficiency low-carbon technology are all conducive to improving the fresh-keeping efforts and benefits of the supply chain;cost-sharing contracts can coordinate the supply chain of fresh agricultural products.

关键词： Dominant power carbon cap-and-trade policy fresh agricultural product supply chain fresh-keeping decision-making

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Overview of radar detection methods for low altitude targets in marine environments

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Journal of Systems Engineering and Electronics 2024年第1期35卷 1-13页

作者： yang Yong yang Boyu School of Electronic Science National University of Defense TechnologyChangsha 410073China

In this paper,a comprehensive overview of radar detection methods for low-altitude targets in maritime environments is presented,focusing on the challenges posed by sea clutter and multipath scattering.The performance of the radar detection methods under sea clutter,multipath,and combined conditions is categorized and summarized,and future research directions are outlined to enhance radar detection performance for low-altitude targets in maritime environments.

关键词： radar sea clutter multipath scattering detection low altitude target

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Deficiency of Trp53 and Rb1 in myeloid cell lineage spontaneously develops acute myeloid leukemia in a mouse model

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Genes & Diseases 2024年第1期11卷 4-6页

作者： yang Li Shu-ting yang Shuying yang Department of Basic&Translational Sciences School of Dental MedicineUniversity of PennsylvaniaPhiladelphiaPA 19104USA Department of Orthopaedic Surgery School of MedicineJohns Hopkins University BaltimoreMD 21205USA Center for Innovation&Precision Dentistry School of Dental MedicineSchool of Engineering and Applied SciencesUniversity of PennsylvaniaPhiladelphiaPA 19104USA The Penn Center for Musculoskeletal Disorders School of MedicineUniversity of PennsylvaniaPhiladelphiaPA 19104USA

Acute myeloid leukemia(AML)is a rapidly lethal blood cancer characterized by aberrant proliferation and differentiation of myeloid progenitors in the hematopoietic tissue.In recent decades,AML patients are significantly increased.In 2019 alone,21,450 new AML cases were diagnosed in the United States,with an estimated 10,920 deaths due to AML.What’s worse,AML occurs with an increasing incidence with advanced age,and the survival rate remains dismal with a median overall survival of only 5e10 months.Notwithstanding great advances in allogenic transplant and chemotherapy,the therapeutic outcomes are unfavorable due to the disease relapse and mortality rates.More importantly,the development of more specific and effective therapies was hampered in part by the lack of proper animal models for AML.Thus,management and elucidation of the pathological mechanism of AML remain an ongoing challenge,and the development of effective AML mouse models and treatment options are urgently needed.

关键词： myeloid Acute leukemia

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The role of exosomes in adult neurogenesis:implications for neurodegenerative diseases

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Neural Regeneration Research 2024年第2期19卷 282-288页

作者： Zhuoyang Yu Yan Teng Jing yang Lu yang Institute of Neurology Sichuan Provincial People’s HospitalUniversity of Electronic Science and Technology of ChinaChengduSichuan ProvinceChina Laboratory of Aging Research School of MedicineUniversity of Electronic Science and Technology of ChinaChengduSichuan ProvinceChina

Exosomes are cup-shaped extracellular vesicles with a lipid bilayer that is approximately 30 to 200 nm in thickness.Exosomes are widely distributed in a range of body fluids,including urine,blood,milk,and saliva.Exosomes exert biological function by transporting factors between different cells and by regulating biological pathways in recipient cells.As an important form of intercellular communication,exosomes are increasingly being investigated due to their ability to transfer bioactive molecules such as lipids,proteins,mRNAs,and microRNAs between cells,and because they can regulate physiological and pathological processes in the central nervous system.Adult neurogenesis is a multistage process by which new neurons are generated and migrate to be integrated into existing neuronal circuits.In the adult brain,neurogenesis is mainly localized in two specialized niches:the subventricular zone adjacent to the lateral ventricles and the subgranular zone of the dentate gyrus.An increasing body of evidence indicates that adult neurogenesis is tightly controlled by environmental conditions with the niches.In recent studies,exosomes released from different sources of cells were shown to play an active role in regulating neurogenesis both in vitro and in vivo,thereby participating in the progression of neurodegenerative disorders in patients and in various disease models.Here,we provide a state-of-the-art synopsis of existing research that aimed to identify the diverse components of exosome cargoes and elucidate the therapeutic potential of exosomal contents in the regulation of neurogenesis in several neurodegenerative diseases.We emphasize that exosomal cargoes could serve as a potential biomarker to monitor functional neurogenesis in adults.In addition,exosomes can also be considered as a novel therapeutic approach to treat various neurodegenerative disorders by improving endogenous neurogenesis to mitigate neuronal loss in the central nervous system.

关键词： adult neurogenesis Alzheimer’s disease amyotrophic lateral sclerosis exosome Huntington’s disease neurodegenerative disease neurogenic niches Parkinson’s disease

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