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siRNA-functionalized lanthanide nanoparticle enables efficient endosomal escape and cancer treatment

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Nano Research 2022年第10期15卷 9160-9168页

作者： Chanchan Yu Kun Li Lin Xu Bo Li Chunhui Li Shuai Guo Ziyue Li Yuquan Zhang Abid Hussain Hong Tan Mengyu Zhang Yongxiang Zhao Yuanyu Huang Xing-Jie Liang School of Life Science Advanced Research Institute of Multidisciplinary ScienceSchool of Medical Technology(Institute of Engineering Medicine)Key Laboratory of Molecular Medicine and BiotherapyKey Laboratory of Medical Molecule Science and Pharmaceutics EngineeringBeijing Institute of TechnologyBeijing 100081China CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety CAS Center for Excellence in NanoscienceNational Center for Nanoscience and Technology of ChinaBeijing 100190China National Center for International Research of Biological Targeting Diagnosis and Therapy Guangxi Key Laboratory of Biological Targeting Diagnosis and Therapy ResearchGuangxi Medical UniversityNanning 530021China

Attaching DNA/RNA to nanomaterials is the basis for nucleic acid-based assembly and drug ***,we report that small interfering RNA(siRNA)effectively coordinates with ligand-free lanthanide nanoparticles(NaGdF4 NPs),and forms siRNA/NaGdF4 spherical nucleic acids(SNA).The coordination is primarily attributed to the interaction between Gd and phosphate backbone of the ***,an efficient encapsulation and rapid endosomal escape of siRNA from the endosome/lysosome were achieved,due to its flexible ability to bound to phospholipid head of endosomal membrane,thereby disrupting the membrane *** to the dual properties of NaGdF4 NPs,siRNA loading,and endosomal escape,siRNA targeting programmed cell death-ligand 1(siPD-L1)/NaGdF4 SNA triggers significant gene silencing in vitro and in vivo,and effectively represses the tumor growth in both CT26 tumor model and 4T1 orthotopic murine model.

关键词： coordination chemistry nuclei acid lanthanide nanomaterials small interfering RNA(siRNA)delivery endosome escape

Transportation of AIE-visualized nanoliposomes is dominated by the protein corona

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National Science Review 2021年第6期8卷 23-33页

作者： Yi-Feng Wang Chunqiu Zhang Keni Yang Yufei Wang Shaobo Shan Yan Yan Kenneth A.Dawson Chen Wang Xing-Jie Liang CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety CAS Center for Excellence in NanoscienceNational Center for Nanoscience and Technology of China University of Chinese Academy of Sciences State Key Laboratory of Medicinal Chemical Biology Key Laboratory of Bioactive Materials of Ministry of Educationand College of Life SciencesNankai University Centre for Bio Nano Interactions School of ChemistryUniversity College Dublin School of Biomolecular and Biomedical Science University College Dublin Guangdong Provincial Education Department Key Laboratory of Nano-Immuno-regulation Tumor Microenvironment The Second Affiliated HospitalGuangzhou Medical University

Liposomes, especially cationic liposomes, are the most common and well-investigated nanocarriers for biomedical applications, such as drug and gene delivery. Like other types of nanomaterials, once liposomes are incubated in a biological milieu, their surface can be immediately cloaked by biological components to form a protein corona, which confers a new ‘biological identity’ and modulates downstream interactions with cells. However, it remains unclear how the protein corona affects the transportation mechanism after liposomes interact with cells. Here, we employed home-made aggregation-induced-emission-visualized nanoliposomes TR4@Lipo as a model to investigate transportation with or without the protein corona by optical imaging techniques. The results show that the protein corona can change the cellular transportation mechanism of TR4@Lipo from energy-independent membrane fusion to energy-dependent *** protein corona also modulates the intracellular distribution of loaded cargoes. This knowledge furthers our understanding of bio-nano interactions and is important for the efficient use of cationic liposomes.

关键词： aggregation-induced emission (AIE) cationic liposomes protein corona endocytosis membrane fusion

Gold nanoparticles combat enveloped RNA virus by affecting organelle dynamics

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Signal Transduction and Targeted Therapy 2023年第9期8卷 4244-4251页

作者： Fangzhou Li Qianqian Huang Ziran Zhou Qiongge Guan Fei Ye Baoying Huang Weisheng Guo Xing-Jie Liang CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety CAS Center for Excellence in NanoscienceNational Center for Nanoscience and Technology of ChinaNo.11First North RoadZhongguancun100190 BeijingP.R.China University of Chinese Academy of Sciences 100049 BeijingP.R.China MHC Key Laboratory of Biosafety National Institute for Viral Disease Control and PreventionChina CDCBeijingChina Department of Minimally Invasive Interventional Radiology the State Key Laboratory of Respiratory DiseaseSchool of Biomedical Engineering&The Second Affiliated HospitalGuangzhou Medical University510260 GuangzhouP.R.China

Enveloped RNA viruses are a group of viruses with an outer membrane derived from a host cell and a genome consisting of ribonucleic acid(RNA).These viruses rely on host cell machinery and organelles to replicate and assemble new virus ***,the interaction between viruses and host organelles may be disrupted by nanomaterials,such as gold nanoparticles(AuNPs)with unique physical and chemical *** this study,we investigated the effects of AuNPs with different surface charge properties on the subcellular structure and function of mammalian cells,and their effects on two representative enveloped RNA viruses:lentivirus and human coronavirus OC43(HCoV-OC43)antiviral *** comparing the subcellular effects of AuNPs with different surface charge properties,we found that treatment with AuNPs with positive surface charges induced more significant disruption of subcellular structures than neutrally charged AuNPs and negatively charged AuNPs,mainly manifested in lysosomes and Cytoskeletal *** antiviral effect of the surface positively charged AuNPs was further evaluated using lentivirus and *** results showed that AuNPs had a significant inhibitory effect on both lentivirus and HCoV-OC43 without obvious side *** conclusion,our study provides insights into the mechanism of action and biocompatibility of AuNP in biological systems,while supporting the potential of targeting organelle dynamics against enveloped RNA viruses.

关键词： properties particles envelope

Effect of physicochemical properties on in vivo fate of nanoparticle-based cancer immunotherapies

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Acta Pharmaceutica Sinica B 2021年第4期11卷 886-902页

作者： Yongchao Wang Jinjin Wang Dandan Zhu Yufei Wang Guangchao Qing Yuxuan Zhang Xiaoxuan Liu Xing-Jie Liang State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases Center of Drug DiscoveryCenter of Advanced Pharmaceutics and BiomaterialsChina Pharmaceutical UniversityNanjing 210009China Laboratory of Controllable Nanopharmaceuticals Chinese Academy of Sciences(CAS)Center for Excellence in Nanoscience and CAS Key Laboratory for Biomedical Effects of Nanomaterials and NanosafetyNational Center for Nanoscience and TechnologyBeijing 100190China University of Chinese Academy of Sciences Beijing 100049China

Current advances of immunotherapy have greatly changed the way of cancer *** the same time,a great number of nanoparticle-based cancer immunotherapies(NBCIs)have also been explored to elicit potent immune responses against ***,few NBCIs are nearly in the clinical trial which is mainly ascribed to a lack understanding of in vivo fate of nanoparticles(NPs)for cancer *** for cancer immunotherapy mainly target the immune organs or immune cells to enable effcient antitumor immune *** physicochemical properties of NPs including size,shape,elasticity and surface properties directly affect their interaction with immune systems as well as their in vivo fate and therapeutic ***,systematic analysis of the physicochemical properties and their effect on in vivo fate is urgently *** this review,we frst recapitulate the fundamentals for the in vivo fate of NBCIs including physio-anatomical features of lymphatic system and strategies to modulate immune ***,we highlight the effect of physicochemical properties on their in vivo fate including lymph nodes(LNs)drainage,cellular uptake and intracellular *** and opportunities for rational design of NPs for cancer immunotherapy are also discussed in detail.

关键词： Physicochemical properties Nanoparticle-based cancer immunotherapies Cancer treatment In vivo fate Immune responses Lymph nodes drainage Cellular uptake Intracellular transfer

维普期刊数据库

Review:Development of SARS-CoV-2 immuno-enhanced COVID-19 vaccines with nano-platform

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Nano Research 2022年第3期15卷 2196-2225页

作者： Nawamin Sa-nguanmoo Katawut Namdee Mattaka Khongkow Uracha Ruktanonchai YongXiang Zhao Xing-Jie Liang CAS Center for Excellence in Nanoscience CAS Key Laboratory for Biomedical Effects of Nanomaterials and NanosafetyNational Center for Nanoscience and Technology of ChinaBeijing 100190China University of Chinese Academy of Sciences Beijing 100049China National Nanotechnology Center(NANOTEC) National Science and Technology Development AgencyPathum Thani 12120Thailand National Center for International Research of Biotargeting Theranostics Guangxi Key Laboratory of Biotargeting TheranosticsCollaborative Innovation Center for Targeting Tumour Theranostics and TherapyGuangxi Medical UniversityNanning 530021China

Vaccination is the most effective way to prevent coronavirus disease 2019(COVID-19).Vaccine development approaches consist of viral vector vaccines,DNA vaccine,RNA vaccine,live attenuated virus,and recombinant proteins,which elicit a specific immune *** use of nanoparticles displaying antigen is one of the alternative approaches to conventional *** is due to the fact that nano-based vaccines are stable,able to target,form images,and offer an opportunity to enhance the immune *** diameters of ultrafine nanoparticles are in the range of 1–100 *** application of nanotechnology on vaccine design provides precise fabrication of nanomaterials with desirable properties and ability to eliminate undesirable *** be successful,nanomaterials must be uptaken into the cell,especially into the target and able to modulate cellular functions at the subcellular *** advantages of nano-based vaccines are the ability to protect a cargo such as RNA,DNA,protein,or synthesis substance and have enhanced stability in a broad range of pH,ambient temperatures,and humidity for long-term ***,nano-based vaccines can be engineered to overcome biological barriers such as nonspecific distribution in order to elicit functions in antigen presenting *** this review,we will summarize on the developing COVID-19 vaccine strategies and how the nanotechnology can enhance antigen presentation and strong immunogenicity using advanced technology in nanocarrier to deliver *** discussion about their safe,effective,and affordable vaccines to immunize against COVID-19 will be highlighted.

关键词： COVID-19 SARS-CoV-2 vaccine nanotechnology antigen presenting cells(APCs)

A micelle-based stage-by-stage impelled system for efficient doxorubicin delivery

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Bioactive Materials 2023年第7期25卷 783-795页

作者： Sunfan Li Fangzhou Li Dong Wan Zuqin Chen Jie Pan Xing-Jie Liang School of Chemical Engineering and Technology Tiangong UniversityTianjin300387PR China CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety CAS Center for Excellence in NanoscienceNational Center for Nanoscience and Technology of ChinaNo.11First North RoadZhongguancunBeijing100190PR China University of Chinese Academy of Sciences Beijing100049PR China Medical School of Chinese PLA No.28 Fuxing RoadBeijing100853PR China Department of Radiology The First Medical CentreChinese PLA General HospitalBeijingPR China Department of Radiology Chinese PAP Guangxi Corps HospitalNanningGuangxiPR China

Chemotherapy remains the mainstay of cancer treatment,benefiting millions of patients each year,but the side effects of chemotherapy drugs severely limit their clinical ***(DOX)can cause various side effects such as heart damage and treatment-related *** effective use of active and passive targeting will improve the clinical application of ***,TPGS3350 and bioactive peptides were utilized to construct a micelle-based stage-by-stage impelled efficient system(missiles)for DOX delivery(DOX missiles).By taking advantage of the EPR effect,DOX missiles are efficiently enriched at the tumor *** being cleaved by matrix metalloproteinase2(MMP2),the peptide(VRGD)targets tumor cells to facilitate uptake of the missiles by the tumor cells via receptor-mediated *** intracellular activated caspase-3-catalyzed explosion of DOX missiles further enables efficient tumor *** study provides an efficient approach for DOX delivery and toxicity reduction.

关键词： Doxorubicin Delivery Peptide Missiles Chemotherapy

Intracellular aggregations of biological elements:From simple to complex

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Aggregate

Aggregate 2021年第3期2卷 14-20页

作者： Fangzhou Li Xinmiao Lan Xing-Jie Liang Laboratory of Controllable Nanopharmaceuticals Chinese Academy of Sciences(CAS)Center for Excellence in Nanoscience and CAS Key Laboratory for Biomedical Effects of Nanomaterials and NanosafetyNational Center for Nanoscience and TechnologyBeijingChina Discipline of Oral and Maxillofacial Surgery Faculty of DentistryThe University of Hong KongHong Kong SARChina University of Chinese Academy of Sciences BeijingChina

Most cellular elements could be functioned by forming aggregate structures through interactions with other molecules,which is like the luminescence mechanism of AIE ***,in comparison to AIE molecules,the aggregation of biological elements appears to be more complex due to membership and mechanism,which is in line with the trend in biological evolution following the principle of simplicity to ***,we chose three distinctive examples because they differ significantly in their composition and show a progression from simple to complex,namely protein–protein complexes,protein–nucleic acid complexes,and protein–nucleic acid–lipid *** majority of units that perform functions within cells belong to these three *** discuss the formation mechanisms and related functions of the protein–protein complex(PML-NB),the proteins–nucleic acids complex ribosome,and the proteins–nucleic acids–lipids complex exosome,and hope to provide expert insight for related fields.

关键词： exosome PML nuclear body PML-NBs ribosome

Pancreatic adenocarcinoma and aging:understanding the menace for better management

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Journal of Pancreatology 2023年第4期6卷 158-168页

作者： Tianxing Zhou Jingrui Yan Jihui Hao Jun Yu Department of Pancreatic Cancer Tianjin Medical University Cancer Institute and HospitalNational Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjinP.R.China Departments of Medicine and Oncology Johns Hopkins University School of MedicineBaltimoreMD

Pancreatic ductal adenocarcinoma(PDAC)is the leading cause of cancer-related death *** PDAC is more common in older adults and the population is aging,the incidence of pancreatic adenocarcinoma is expected to increase in the coming *** a result,the mechanism and clinical management of PDAC in the elderly population is receiving more *** review will discuss age-related morphological and pathological changes,clinical management,surgery and adjuvant therapies,and molecular changes in elderly PDAC *** research is needed to clarify molecular mechanisms and develop new prevention and treatment strategies for PDAC in elderly patients.

关键词： Aging Chemotherapy PDAC Radiation Senescence Surgery

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Ferritin-based drug delivery system for tumor therapy

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BMEMat(BioMedical Engineering Materials) 2023年第2期1卷 1-10页

作者： Zaiqian Tu Peter Timashev Junge Chen Xing-Jie Liang CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety CAS Center for Excellence in NanoscienceNational Center for Nanoscience and Technology of ChinaBeijingChina Laboratory of Clinical Smart Nanotechnologies Institute for Regenerative MedicineSechenov UniversityMoscowRussia beijing Advanced Innovation Center for Biomedical Engineering School of Engineering Medicine&Shenzhen Institute of Beihang UniversityBeihang UniversityBeijingChina

Ferritin has been widely used in drug delivery in recent years due to its unique spherical nanocage *** addition,the natural targeting and good biocompatibility of ferritin make it an excellent drug delivery ***,ferritin has shown a broad application prospect in the field of *** this perspective,we will describe ferritin-based drug delivery system,ferritin-based drug delivery system for tumor treatment,and future challenges in ferritin ***,this perspective may inspire the future development of ferritin-based drug delivery systems for tumor treatment.

关键词： drug delivery ferritin tumor therapy