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Principles of Nanoparticle Delivery to Solid Tumors

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Biomedical Engineering Frontiers 2023年第1期4卷 177-186页

作者： Warren C.W.Chan Institute of Biomedical Engineering University of TorontoTorontoON M5S 3G9Canada.Terrence Donnelly Center for Cellular&Biomolecular ResearchUniversity of TorontoTorontoON M53E1Canada.Department of ChemistryUniversity of TorontoTorontoON M5S 3H6Canada

The effective treatment of patients with cancer hinges on the delivery of therapeutics to a tumor *** provide an essential transport *** present 5 principles to consider when designing nanoparticles for cancer targeting:(a)Nanoparticles acquire biological identity in vivo,(b)organs compete for nanoparticles in circulation,(c)nanoparticles must enter solid tumors to target tumor components,(d)nanoparticles must navigate the tumor microenvironment for cellular or organelle targeting,and(e)size,shape,surface chemistry,and other physicochemical properties of nanoparticles influence their transport process to the *** review article describes these principles and their application for engineering nanoparticle delivery systems to carry therapeutics to tumors or other disease targets.

关键词： organs cancer carry

Global Landscape of Native Protein Complexes in Synechocystis *** 6803

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Genomics, Proteomics & Bioinformatics 2022年第4期20卷 715-727页

作者： Chen Xu Bing Wang Lin Yang Lucas Zhongming Hu Lanxing Yi Yaxuan Wang Shenglan Chen Andrew Emili Cuihong Wan School of Life Sciences and Hubei Key Laboratory of Genetic Regulation and Integrative Biology Central China Normal UniversityWuhan 430079China donnelly centre for cellular and biomolecular research University of TorontoTorontoON M5S 2E8Canada Departments of Biochemistry and Biology Boston UniversityBostonMA 02215USA

Synechocystis *** 6803(hereafter:Synechocystis)is a model organism for studying photosynthesis,energy metabolism,and environmental *** known as the first fully sequenced phototrophic organism,Synechocystis still has almost half of its proteome without functional *** this study,by using co-fractionation coupled with liquid chromatographytandem mass spectrometry(LC-MS/MS),we define 291 multi-protein complexes,encompassing24,092 protein±protein interactions(PPIs)among 2062 distinct gene *** information not only reveals the roles of photosynthesis in metabolism,cell motility,DNA repair,cell division,and other physiological processes,but also shows how protein functions vary from bacteria to higher plants due to changes in interaction *** also allows us to uncover the functions of hypothetical proteins,such as Sll0445,Sll0446,and Sll0447 involved in photosynthesis and cell motility,and Sll1334 involved in regulation of fatty acid *** we present the most extensive PPI data for Synechocystis so far,which provide critical insights into fundamental molecular mechanisms in cyanobacteria.

关键词： Protein–protein interaction Cyanobacterium Co-fractionation Photosynthesis Function prediction

Stem cell heterogeneity and regenerative competence:the enormous potential of rare cells

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Neural Regeneration research 2021年第2期16卷 285-286页

作者： Emily A.B.Gilbert Cindi M.Morshead Terrence donnelly centre for cellular and biomolecular research Division of AnatomyDepartment of SurgeryUniversity of TorontoTorontoONCanada Institute of Biomedical and Biochemical Engineering Institute of Medical ScienceUniversity of TorontoKITEToronto Rehabilitation InstituteUniversity Health NetworkTorontoONCanada

Reconstitution of complex multi-tissue organs is one of the most impressive feats of biology and is observed across regeneration-competent vertebrate species,including teleost fish(e.g.,zebrafish),urodeles(e.g.,axolotls and newts),and some *** ability within these species ranges from muscle(including cardiac),skeletal structures,to complex systems such as the brain,spinal cord and parts of the eye which are all capable of structural and functional repair following injury(Tanaka and Ferretti,2009).In stark contrast,re-establishment of multi-tissue structures is very rarely observed following embryogenesis in regeneration-incompetent *** of digit tips is the most dramatic example of mammalian regeneration,but pales in comparison to other species in the animal ***,a complete recapitulation of complex organs or structures in mammals will remain out of reach for a considerable time;however,an improved understanding of regenerat i ve mechanisms would likely enhance the development of novel regenerative medicine *** we focus on the diversity and commonalities of stem cells,which could underlie complex tissue regeneration.

关键词： organs rare potential

The influence of nanotopography on cell behaviour through interactions with the extracellular matrix-A review

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Bioactive Materials 2022年第9期7卷 145-159页

作者： Jiajun Luo Matthew Walker Yinbo Xiao Hannah donnelly Matthew J.Dalby Manuel Salmeron-Sanchez centre for the cellular Microenvironment University of GlasgowGlasgowG128LTUK

Nanotopography presents an effective physical approach for biomaterial cell manipulation mediated through material-extracellular matrix *** extracellular matrix that exists in the cellular microenvironment is crucial for guiding cell behaviours,such as determination of integrin ligation and interaction with growth *** interactions with the extracellular matrix regulate downstream mechanotransductive pathways,such as rearrangements in the cytoskeleton and activation of signal *** adsorption onto nanotopography strongly influences the conformation and distribution density of extracellular matrix and,therefore,subsequent cell *** this review,we first discuss the interactive mechanisms of protein physical adsorption on ***,we summarise advances in creating nanotopographical features to instruct desired cell ***,we focus on the cellular mechanotransductive pathways initiated by *** review provides an overview of the current state-of-the-art designs of nanotopography aiming to provide better biomedical materials for the future.

关键词： Nanotopography Cell-material interaction Protein adsorption Biomaterials

BaTiO_(3)@Au nanoheterostructure suppresses triple-negative breast cancer by persistently disrupting mitochondrial energy metabolism

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Nano research 2023年第2期16卷 2775-2785页

作者： Yanlin Feng Jianlin Wang Xin Ning Aiyun Li Qing You Wanzhen Su Deping Wang Jianyun Shi Lan Zhou Fangfang Cao Xiaoyuan Chen Jimin Cao Key Laboratory of cellular Physiology at Shanxi Medical University Ministry of Educationand the Department of PhysiologyShanxi Medical UniversityTaiyuan 030001China Departments of Diagnostic Radiology SurgeryChemical and Biomolecular Engineeringand Biomedical EngineeringYong Loo Lin School of Medicine and Faculty of EngineeringNational University of SingaporeSingapore 119074Singapore Clinical Imaging research centre Centre for Translational MedicineYong Loo Lin School of MedicineNational University of SingaporeSingapore 117599Singapore Nanomedicine Translational research Program NUS Center for NanomedicineYong Loo Lin School of MedicineNational University of SingaporeSingapore 117597Singapore

Abnormal metabolism has become a potential target for highly malignant and invasive triple-negative breast cancer(TNBC)due to its relatively low response to traditional *** existing metabolic interventions demonstrated unsatisfactory therapeutic outcomes and potential systemic toxicity,resulting from the metabolic instability and limited targeting ability of inhibitors as well as complex tumor *** address these limitations,here we developed a robust pyroelectric BaTiO_(3)@Au core–shell nanostructure(BTO@Au)to selectively and persistently block energy generation of tumor *** by near-infrared(NIR)laser,the Au shell could generate heat to activate the BaTiO_(3)core to produce reactive oxygen species(ROS)regardless of the constrained microenvironment,thus prominently inhibits mitochondrial oxidative phosphorylation(OXPHOS)and reduces ATP production to induce TNBC cell *** therapeutic effects have been well demonstrated in vitro and in vivo,paving a new way for the development of metabolic interventions.

关键词： pyroelectric nanoheterostructure reactive oxidative species(ROS) metabolic interventions mitochondrial oxidative phosphorylation(OXPHOS) triple-negative breast cancer(TNBC)

Fibroadhesive scarring of grafted collagen scaffolds interferes with implant–host neural tissue integration and bridging in experimental spinal cord injury

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Regenerative Biomaterials 2019年第2期6卷 75-87页

作者： Haktan Altinova Sebastian Hammes Moniek Palm Jose Gerardo-Nava Pascal Achenbach Ronald Deumens Emmanuel Hermans Tobias Fuhrmann Arne Boecker Sabien Geraldine Antonia van Neerven Ahmet Bozkurt Joachim Weis Gary Anthony Brook Department of Neurosurgery RWTH Aachen University HospitalAachenGermany Institute of Neuropathology RWTH Aachen University HospitalAachenGermany Police Headquarters Berlin Medical CommissionBerlinGermany Institute of Neuroscience Universite Catholique de LouvainBrusselsBelgium donnelly centre for cellular&biomolecular research University of TorontoTorontoCanada Department of Hand- Plastic and Reconstructive SurgeryBurn Centre Trauma CentreBG Trauma Centre LudwigshafenUniversity of HeidelbergLudwigshafenGermany Department of Plastic Reconstructive and Hand SurgeryBurn CentreRWTH Aachen University HospitalAachenGermany Department of Plastic AestheticHand and Burn SurgeryHelios University Hospital WuppertalUniversity Witten/HerdeckeWuppertalGermany

Severe traumatic spinal cord injury(SCI)results in a devastating and permanent loss of function,and is currently an incurable *** is generally accepted that future intervention strategies will require combinational approaches,including bioengineered scaffolds,to support axon growth across tissue scarring and cystic ***,we demonstrated that implantation of a microporous type-I collagen scaffold into an experimental model of SCI was capable of supporting functional recovery in the absence of extensive implant–host neural tissue ***,we demonstrate the reactive host cellular responses that may be detrimental to neural tissue integration after implantation of collagen scaffolds into unilateral resection injuries of the adult rat spinal *** demonstrated scattered fibroblast-like cell infiltration throughout the scaffolds as well as the presence of variable layers of densely packed cells,the fine processes of which extended along the graft–host *** reactive astroglial or regenerating axonal profiles could be seen traversing this *** encapsulation-type behaviour around bioengineered scaffolds impedes the integration of host neural tissues and reduces the intended bridging role of the *** of the cellular and molecular mechanisms underpinning this behaviour will be pivotal in the future design of collagen-based bridging scaffolds intended for regenerative medicine.

关键词： spinal cord injury CNS-scarring type-I collagen scaffold astrogliosis fibrosis encapsulation

Influence of light pattern thickness on the manipulation of dielectric microparticles by optoelectronic tweezers

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Photonics research 2022年第2期10卷 550-556页

作者： Shuailong Zhang Mohamed Elsayed Ran Peng Yujie Chen Yanfeng Zhang Steven L.Neale Aaron R.Wheeler School of Mechatronical Engineering Beijing Institute of TechnologyBeijing 100081China Beijing Advanced Innovation Center for Intelligent Robots and Systems Beijing Institute of TechnologyBeijing 100081China Department of Chemistry University of TorontoTorontoOntario M5S 3H6Canada Institute of Biomedical Engineering University of TorontoTorontoOntario M5S 3G9Canada donnelly centre for cellular and biomolecular research University of TorontoTorontoOntario M5S 3E1Canada Department of Marine Engineering Dalian Maritime UniversityDalian 116026China State Key Laboratory of Optoelectronic Materials and Technologies School of Electronics and Information TechnologySun Yat-sen UniversityGuangzhou 510275China James Watt School of Engineering University of GlasgowGlasgow G128QQUK

Optoelectronic tweezer(OET) is a useful optical micromanipulation technology that has been demonstrated for various applications in electrical engineering and most notably cell selection for biomedical engineering. In this work, we studied the use of light patterns with different shapes and thicknesses to manipulate dielectric microparticles with OET. It was demonstrated that the maximum velocities of the microparticles increase to a peak and then gradually decrease as the light pattern’s thickness increases. Numerical simulations were run to clarify the underlying physical mechanisms, and it was found that the observed phenomenon is due to the co-influence of horizontal and vertical dielectrophoresis forces related to the light pattern’s thickness. Further experiments were run on light patterns with different shapes and objects with different sizes and structures. The experimental results indicate that the physical mechanism elucidated in this research is an important one that applies to different light pattern shapes and different objects, which is useful for enabling users to optimize OET settings for future micromanipulation applications.

关键词： pattern dielectric light

Current Status and Prospect of Stent Placement for May-Thurner Syndrome

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Current Medical Science 2021年第6期41卷 1178-1186页

作者： Qin LIU Fang LIU Ping LÜ Hong-xiao WU Pin YE Yun YOU Zhong YAO Department of Vascular Surgery Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430022China Department of Nuclear Medicine Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430022China donnelly centre for cellular and biomolecular research University of TorontoTorontoOntario M5S 2E8Canada

Stent implantation has been proven to be safe and has become the first-line intervention for May-Thumer syndrome(MTS),with satisfactory mid-term patency rates and clinical *** research has demonstrated that catheter-directed thrombolysis is the preferred strategy when MTS is combined with deep vein thrombosis after self-expanding stent ***,the stent used for the venous system was developed based on the experience obtained in the treatment of arterial ***,relatively common corresponding complications may come along later,which include stent displacement,deformation,and *** measures such as adopting a stent with a larger diameter,improving stent flexibility,and increasing stent strength have been employed in order to prevent these *** ideal venous stent is presently being evaluated and will be introduced in detail in this review.

关键词： May-Thumer syndrome deep vein thrombosis post-thrombotic syndromes stent stent placement

Identification of common and distinct origins of human serum and breastmilk IgA1 by mass spectrometry-based clonal profiling

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cellular & Molecular Immunology 2023年第1期20卷 26-37页

作者： Kelly A.Dingess Max Hoek Danique M.Hvan Rijswijk Sem Tamara Maurits Aden Boer Tim Veth Mirjam J.A.Damen Arjan Barendregt Michelle Romijn Hannah G.Juncker Britt Jvan Keulen Gestur Vidarsson Johannes Bvan Goudoever Albert Bondt Albert J.R.Heck biomolecular Mass Spectrometry and Proteomics Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical SciencesUniversity of UtrechtPadualaan 8Utrecht 3584 CHThe Netherlands Netherlands Proteomics Center Padualaan 8Utrecht 3584 CHThe Netherlands Amsterdam UMC Vrije UniversiteitUniversity of AmsterdamEmma Children’s HospitalAmsterdam Reproduction&Development Research InstituteDepartment of PediatricsAmsterdamthe Netherlands Department of Experimental Immunohematology Sanquin Research and Landsteiner LaboratoryAmsterdam UMCUniversity of AmsterdamAmsterdamNetherlands

The most abundant immunoglobulin present in the human body is IgA. It has the highest concentrations at the mucosal lining and in biofluids such as milk and is the second most abundant class of antibodies in serum. We assessed the structural diversity and clonal repertoire of IgA1-containing molecular assemblies longitudinally in human serum and milk from three donors using a mass spectrometry-based approach. IgA-containing molecules purified from serum or milk were assessed by the release and subsequent analysis of their Fab fragments. Our data revealed that serum IgA1 consists of two distinct structural populations, namely monomeric IgA1 (∼80%) and dimeric joining (J-) chain coupled IgA1 (∼20%). Also, we confirmed that IgA1 in milk is present solely as secretory (S)IgA, consisting of two (∼50%), three (∼33%) or four (∼17%) IgA1 molecules assembled with a J-chain and secretory component (SC). Interestingly, the serum and milk IgA1-Fab repertoires were distinct between monomeric, and J-chain coupled dimeric IgA1. The serum dimeric J-chain coupled IgA1 repertoire contained several abundant clones also observed in the milk IgA1 repertoire. The latter repertoire had little to no overlap with the serum monomeric IgA1 repertoire. This suggests that human IgA1s have (at least) two distinct origins;one of these produces dimeric J-chain coupled IgA1 molecules, shared in human serum and milk, and another produces monomeric IgA1 ending up exclusively in serum.

关键词： Antigen binding fragment Immunoglobulin A1 Clonal repertoires human milk Serum