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Targeted nanoparticles for the non-invasive detection of traumatic brain injury by optical imaging and fluorine magnetic resonance imaging

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Nano Research 2016年第5期9卷 1276-1289页

作者： Luis Javier Cruz Ivo Que Markus Aswendt Alan Chan Mathias Hoehn Clemens Lowik nanomedicine and Molecular Imaging Department of Radiology Leiden University Medical Center 2333ZA Leiden the Netherlands In-Vivo-NMR Laboratory Max Planck Institute for Neurological Research Cologne D-50931 Cologne Germany Percuros 7522NB Enschede the Netherlands

Necrosis is a form of cell death that occurs only under pathological conditions such as ischemic diseases and traumatic brain injury （TBI）. Non-invasive imaging of the affected tissue is a key component of novel therapeutic interventions and measurement of treatment responses in patients. Here, we report a bimodal approach for the detection and monitoring of TBI. PEGylated poly（lactic-coglycolic acid）（PLGA） nanoparticles （NPs）, encapsulating both near infrared （NIR） fluorophores and perfluorocarbons （PFCs）, were targeted to necrotic ceils. We used cyanine dyes such as IRDye 800CW, for which we have previously demonstrated specific targeting to intracellular proteins of cells that have lost membrane integrity. Here, we show specific in vivo detection of necrosis by optical imaging and fluorine magnetic resonance imaging （^19F MRI） using newly designed PLGA NP（NIR700 ＋ PFC）-PEG-800CW. Quantitative ex vivo optical imaging and ^19F MR spectroscopy of NIR-PFC content in injured brain regions and in major organs were well correlated. Both modalities allowed the in vivo identification of necrotic brain lesions in a mouse model of TBI, with optical imaging being more sensitive than ^19F MRI. Our results confirm increased blood pool residence time of PLGA NPs coated with a PEG layer and the successful targeting of TBI-damaged tissue. A single PLGA NP containing NIR-PFC enables both rapid qualitative optical monitoring of the TBI state and quantitative 3D information from deeper tissues on the extent of the lesion by MRI. These necrosis-targeting PLGA NPs can potentially be used for clinical diagnosis of brain injuries.

关键词： imaging nanoparticles contrast agents magnetic resonance imaging brain injury stroke

Controllable phase transformation and improved thermal stability of nickel on tungsten substrate by electrodeposition

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Journal of Materials Science & Technology 2019年第5期35卷 727-732页

作者： Minjie Xu Chao Hu Haiyan Xiang Haozi Lu Travis Shihao Hu Bonian Hu Song Liu Gang Yu institute of Chemical Biology and nanomedicine (ICBN) State Key Laboratory of Chemical/Biosensing and Chemometrics College of Chemistry and Chemical Engineering Hunan UniversityChangsha410082China Department of Mechanical Engineering California State University Los AngelesCA90032USA Department of Materials and Chemical Engineering Hunan Institute of Technology Hunan Hengyang 421002 China

Present study reports a controllable phase transformation of nickel(Ni) from amorphous to cubic crystal structures on tungsten(W) substrate by electrodeposition. X-ray powder diffraction, scanning electron microscopy, transmission electron microscopy and energy dispersive spectroscopy were used to characterize the microstructure, micro-constituents and surface morphology of as-prepared Ni. The microstructure of Ni was strongly affected by the applied overpotential and deposition time. It is demonstrated that by controlling these two parameters either amorphous or cubic crystal structure of Ni on the W substrate could be obtained. The crystallization mechanism is discussed based on Gibbs crystal growth theory and Ostwald’s rule. It is concluded that W substrate, acting as a heat sink, can effectively promote the thermal stability of amorphous Ni, based on the data from differential scanning calorimetry and Kissinger’s model. This work contributes to the elucidation of the crystallization mechanism of Ni on W powder substrates, and proves that, better than alloying with other elements, incorporating powder substrates will significantly improve the crystallization temperature, hence the thermostability of amorphous Ni.

关键词： Phase transformation Amorphous Ni Electrodeposition Electrocrystallization Thermal stability

Recent progress in engineering near-infrared persistent luminescence nanoprobes for time-resolved biosensing/bioimaging

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Nano Research 2019年第6期12卷 1279-1292页

作者： Ling Liang Na Chen Yiyi Jia Qinqin Ma Jie Wang Quan Yuan Weihong Tan Molecular Science and Biomedicine Laboratory Institute of Chemical Biology and NanomedicineCollege of Chemistry and Chemical EngineeringHunan UniversityChangsha 410082China Key Laboratory of Analytical Chemistry for Biology and Medicine(Ministry of Education) College of Chemistry and Molecular SciencesWuhan UniversityWuhan 430072China

Persistent luminescence nanoprobes (PLNPs) can remain luminescent after ceasing *** to the ultra-long decay time of persistent luminescence (PersL),autofluorescence interference can be efficiently eliminated by collecting PersL signal after autofluorescence decays completely,thus the imaging contrast and sensing sensitivity can be significantly *** near-infrared (NIR) light shows reduced scattering and absorption coefficient in penetrating biological organs or tissues,near-infrared persistent luminescence nanoprobes (NIR PLNPs) possess deep tissue penetration and offer a bright prospect in the areas of in vivo biosensing/*** this review,we firstly summarize the design of different types of NIR PLNPs for biosensing/bioimaging,such as transition metal ions-doped NIR PLNPs,lanthanide ions-doped NIR PLNPs,organic molecules-based NIR PLNPs,and semiconducting polymer self-assembled NIR ***,organic molecules-based NIR PLNPs and semiconductor self-assembled NIR PLNPs,for the first time,were introduced to the review of ***,the effects of different types of charge carriers on NIR PersL and luminescence decay of NIR PLNPs are significantly emphasized so as to build up an in-depth understanding of their luminescence *** includes the regulation of valence band and conduction band of different host materials,alteration of defect types,depth and concentration changes caused by ion doping,effective radiation transitions and energy transfer generated by different luminescence *** the design and potential of NIR PLNPs as long-lived luminescent materials,the current challenges and future perspective in this rapidly growing field are also discussed.

关键词： near-infrared persistent luminescence nanoprobes biosensing bioimaging

Phospholipid membrane-decorated deep-penetrated nanocatalase relieve tumor hypoxia to enhance chemo-photodynamic therapy

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Acta Pharmaceutica Sinica B 2020年第11期10卷 2246-2257页

作者： Junjing Yin Haiqiang Cao Hong Wang Kaoxiang Sun Yaping Li Zhiwen Zhang School of Pharmacy Yantai UniversityYantai 264005China State Key Laboratory of Drug Research&Center of Pharmaceutics Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China Yantai Key Laboratory of nanomedicine&Advanced Preparations Yantai Institute of Materia MedicaYantai 264000China

Hypoxia is a serious impediment to current treatments of many malignant ***,an antioxidant enzyme,is capable of decomposing endogenous hydrogen peroxide(H2O2)into oxygen for tumor reoxygenation,but suffered from in vivo instability and limited delivery to deep interior hypoxic regions in ***,a deep-penetrated nanocatalase-loading DiIC18(5,DiD)and soravtansine(Cat@PDS)were provided by coating catalase nanoparticles with PEGylated phospholipids membrane,stimulating the structure and function of erythrocytes to relieve tumor hypoxia for enhanced chemophotodynamic *** intravenous administration,Cat@PDS preferentially accumulated at tumor sites,flexibly penetrated into the interior regions of tumor mass and remarkably relieved the hypoxic status in ***,the Cat@PDS+laser treatment produced striking inhibition of tumor growth and resulted in a 97.2%suppression of lung ***,the phospholipids membrane-coated nanocatalase system represents an encouraging nanoplatform to relieve tumor hypoxia and synergize the chemophotodynamic cancer therapy.

关键词： Photodynamic therapy Tumor hypoxia Catalase Tumor penetration Drug delivery Nanoparticle Tumor targeting Cancer metastasis Cancer therapy

High stability three-dimensional porous PtSn nano-catalyst for ethanol electro-oxidation reaction

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Chinese Chemical Letters 2020年第9期31卷 2491-2494页

作者： Yue Sun Haiyan Xiang Huimin Li Gang Yu Hong Chen Song Liu institute of Chemical Biology and nanomedicine(ICBN) State Key Laboratory of Chemo/Biosensing and ChemometricsCollege of Chemistry and Chemical EngineeringHunan UniversityChangsha 410082China School of Materials Science and Energy Engineering Foshan UniversityFoshan 528000China

In addition to the theoretical research,direct ethanol fuel cells have great potential in practical *** performance of direct ethanol fuel cells largely depends on the *** electrocatalysts have been promising candidates for advancing direct ethanol fuel cells for its high catalytic activity and great ***,a PtSn catalyst with unique three-dimensional porous nanostructure has been designed and synthesized via a two-step liquid phase reduction *** formed a self-supporting framework in PtSn alloy particles(~3.5 nm).In ethanol electro-oxidation reaction,the PtSn catalyst exhibited high mass activity and excellent recycling time compared with that of Pt/*** the morphology characterization before and after potential cycling,the PtSn alloy-based nano-catalyst showed good *** PtSn catalysts effectively avoid structural instability due to the external carriers,and prolong the leaching time of *** addition,the introduction of a certain amount of Sn can also solve the poisoning phenomenon of active sites on Pt *** design strategy of porous alloy nano-catalyst sheds light on its applications in direct ethanol fuel cells.

关键词： PtSn Porous structure Direct ethanol fuel cell Ethanol electro-oxidation Stability

Highly biocompatible BSA-MnO_2 nanoparticles as an efficient near-infrared photothermal agent for cancer therapy

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Chinese Chemical Letters 2018年第11期29卷 1685-1688页

作者： Yuzhen Wang Yujun Song Guixian Zhu Dechen Zhang Xuewu Liu Key Laboratory of Flexible Electronics (KLOFE) & institute of Advanced Materials (IAM) Jiangsu National Synergistic Innovation Center for Advanced Materials (SICAM)Nanjing Tech University (NanjingTech) Department of Biomedical Engineering College of Engineering and Applied SciencesNanjing University Department of nanomedicine Houston Methodist Research Institute

More recently, the biomedical applications of MnO2 in bioanalysis, cell imaging, and drug delivery as a result of their appealing physicochemical properties, have been reported and expanded rapidly. However, research on a near infrared （NIR） photothermal response of MnO2 was ignored. In this work, we reported a facile, one-pot method to synthesis of bovine serum albumin （BSA）-reduced and stabilized MnO2 nanoparticles （BSA-MnO2 NPs） with good aqueous dispersibility and high biocompatibility. And we also showed for the first time that BSA-MnO2 NPs displayed superior NIR photothermal efficiency and photostability which demonstrated as a novel class of photothermal antitumor agent.

关键词： Bovine serum albumin Manganese dioxide Photothermal NIR Cancer therapy

Biomedical applications of mRNA nanomedicine

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Nano Research 2018年第10期11卷 5281-5309页

作者： Qingqing Xiong Gha Young Lee Jianxun Ding Wenliang Li Jinjun Shi Center for nanomedicine and Department of Anesthesiology Brigham and Women's Hospital Harvard Medical School Boston MA 02115 USA Department of Hepatobiliary Cancer Tianjin Medical University Cancer Institute & Hospital Tianjin 300060 China School of Pharmacy Jilin Medical University Jilin 132013 China

As an attractive alternative to plasmid DNA, messenger RNA （mRNA） has recently emerged as a promising class of nucleic acid therapeutics for biomedical applications. Advances in addressing the inherent shortcomings of mRNA and in the development of nanoparticle-based delivery systems have prompted the development and clinical translation of mRNA-based medicines. In this review, we discuss the chemical modification strategies of mRNA to improve its stability, minimize immune responses, and enhance translational efficacy. We also highlight recent progress in nanoparticle-based mRNA delivery. Considerable attention is given to the increasingly widespread applications of mRNA nanomedicine in the biomedical fields of vaccination, protein-replacement therapy, gene editing, and cellular reprogramming and engineering.

关键词： messenger RNA chemical modification nanoparticle vaccination gene editing protein-replacement cellular reprogramming and engineering

Discovery of Novel Long-Chain Alkenyl Diacid Derivatives as ACLY Inhibitors

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Chinese Journal of Chemistry 2022年第22期40卷 2663-2670页

作者： Gao-Lei Song Lei Cao Mei Zhang Yu-Rou Yang Jie Ma Zhi-Fu Xie Jing-Ya Li Fa-Jun Nan State Key Laboratory of Drug Research Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China University of Chinese Academy of Sciences No.19A Yuquan RoadBeijing 100049China Yantai Key Laboratory of nanomedicine&Advanced Preparations Yantai Institute of Materia MedicaYantaiShandong 264000China

ATP citrate lyase(ACLY)synthesizes cytosolic acetyl coenzyme A(acetyl-CoA),an essential biosynthetic precursor for lipid synthesis and the acetyl donor required for protein *** aberrant expression and activity of ACLY has been documented in multiple human ***-1002 is an indirect ACLY inhibitor,and it has recently been approved by the FDA as an additional therapeutic option in high-risk hypercholesterolemia patients unable to meet goals with standard *** this work,we identified a series of novel long-chain alkenyl diacids as potent direct ACLY inhibitors,and comprehensive structure-activity relationship analysis showed that compound 18f was the most potent ACLY inhibitor with an IC50 value of 1.5μmol/*** ester formation of 18f gave a new series of compounds such as 25f that maintained ACLY inhibitory activity and improved antitumor cell proliferation effects.

关键词： Alkenyl diacid derivatives Cancer ACLY inhibitors Acetyl-CoA Structure-activity relationships

Bioengineering Functional Copolymers. XVII. Interaction of Organoboron Amide-Ester Branched Derivatives of Poly(Acrylic Acid) with Cancer Cells

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Journal of Cancer Therapy 2011年第2期2卷 266-275页

作者： Mustafa Türk Gülten Kahraman Sevda A. Khalilova Zakir M. O. Rzayev Serpil Oguztüzün institute of Science & Engineering Division of Nanoscience and Nanomedicine Hacettepe University Ankara Turkey.

Novel bioengineering functional organoboron polymers were synthesized by 1) amidolysis of poly(acrcylic acid) (PAA) with 2-aminoethyldiphenyl borinate (2-AEPB), 2) esterification of organoboron PAA polymer (PAA-B) with a-hydroxy-methoxypoly(ethylene oxide) (PEO) as a compatibilizer and 3) conjugation of organoboron PEO branches (PAA-B-PEO) with folic acid (FA) as a targeting agent. Structure and composition of the synthesized polymers were characterized by FTIR-ATR and 1H (13C) NMR spectroscopy, chemical and physical analysis methods. Anti-tumor activity of organoboron functional polymer and its complex with FA (PAA-B-PEO-F) against cancer and normal cells were evaluated by using different biochemical methods such as cytotoxicity, statistical, apoptotic and necrotic cell indexes, double staining and caspase-3 immune staining, light and fluorescence inverted microscope analyses. It was found that citotoxicity and apoptotic/necrotic effects of polymers significantly depend on the structure and composition of studied polymers, and increase the following raw: PAA << PAA-B < PAA-B-PEO < PAA-B-PEO-F. Among them, PAA-B-PEO-F complex at 400 mg mL–1 concentration as a therapeutic drug exhibits minimal toxicity toward the nor-mal cells, but influential for HeLa cancer cells.

关键词： Synthesis Amidolysis Organoboron Polymers Conjugation Citotoxicity Apoptotic and Necrotic Effects