Multimodal nanoparticles (gold in polylactide) and their effect on three-dimensional cell cultures as organ models

多峰纳米颗粒(聚丙交酯中的金)及其对作为器官模型的三维细胞培养物的影响

基本信息

项目摘要

We will synthesise multimodal nanoparticles that can be tracked in the cell and detected in the endo-lysosome by specific fluorescence labels. This will be achieved by covalently binding fluorescently labelled biomolecules to small gold nanoparticles (diameter approx. 10 nm) where their fluorescence is quenched. These will be incorporated into polylactide-co-glycolide (PLGA) particles (estimation: approximately 10 gold nanoparticles within a single PLGA particle with a diameter of around 100 nm). The PLGA envelope will also be covalently functionalised with fluorescent dyes. The cellular uptake of the multimodal nanoparticles will be studied quantitatively using 3D cell culture models (crypt organoids and tumour spheroids) by in situ confocal laser scanning microscopy. We will focus on the pathway of the nanoparticles inside the complex cell network of the 3D cell culture or organoids and investigate the impact of the multimodal nanoparticles and biomolecules. Biomolecules for gene silencing (siRNA) will be conjugated to the gold nanoparticles to achieve a biological effect. First, the gene silencing of fluorescent eGFP as model protein will be investigated, followed by the gene silencing of important inflammatory disease mediators, such as TNF-α, KC, IP 10, and the apoptosis-inhibiting survivin as an additional protein model. The nanoparticle-mediated gene silencing of survivin will prove and extend our concept to another therapeutically relevant target.In summary, we aim for a better understanding of the biological effects of functional nanoparticles, covering inter alia the questions of dose, pathway, and fate. Three-dimensional cell culture models shall serve as bridge between "classical" two-dimensional cell cultures and animal models. We also want to achieve a quantitative validation of two-dimensional and three-dimensional cell culture models with respect to biologically active nanoparticles.
我们将合成多模态纳米颗粒,可以在细胞中被跟踪,并通过特定的荧光标记在内切溶酶体中被检测到。这将通过将荧光标记的生物分子共价结合到小的金纳米颗粒(直径约。10nm),它们的荧光被淬灭。这些将被纳入聚乳酸-共聚物(PLGA)颗粒中(估计:大约10个金纳米颗粒在一个直径约100纳米的PLGA颗粒中)。PLGA包膜也将与荧光染料共价功能化。多模态纳米颗粒的细胞摄取将通过原位共聚焦激光扫描显微镜使用3D细胞培养模型(隐窝类器官和肿瘤球体)进行定量研究。我们将重点关注纳米颗粒在3D细胞培养或类器官的复杂细胞网络中的途径,并研究多模态纳米颗粒和生物分子的影响。用于基因沉默的生物分子(siRNA)将被偶联到金纳米颗粒上以实现生物效应。首先,将研究荧光eGFP作为模型蛋白的基因沉默,然后研究重要炎症疾病介质的基因沉默,如TNF-α、KC、IP 10和抑制凋亡的survivin作为额外的蛋白质模型。纳米颗粒介导的基因沉默将证明并扩展我们的概念到另一个治疗相关的靶标。总之,我们的目标是更好地了解功能性纳米颗粒的生物学效应,包括剂量、途径和命运等问题。三维细胞培养模型应作为“经典”二维细胞培养和动物模型之间的桥梁。我们还希望实现二维和三维细胞培养模型的定量验证与生物活性纳米颗粒。

项目成果

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Professor Dr. Matthias Epple其他文献

Professor Dr. Matthias Epple的其他文献

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{{ truncateString('Professor Dr. Matthias Epple', 18)}}的其他基金

Multifunctional calcium phosphate nanoparticles as novel HIV-1 vaccine platform
多功能磷酸钙纳米颗粒作为新型 HIV-1 疫苗平台
  • 批准号:
    432828510
  • 财政年份:
    2019
  • 资助金额:
    --
  • 项目类别:
    Research Grants
Nanoparticle-induced gene-silencing for the suppression of inflammation in mouse models (edema, scleroderma, sepsis)
纳米颗粒诱导的基因沉默可抑制小鼠模型中的炎症(水肿、硬皮病、脓毒症)
  • 批准号:
    382633364
  • 财政年份:
    2017
  • 资助金额:
    --
  • 项目类别:
    Research Grants
Bimetallic nanoparticles of the platinum metals (Ru, Rh, Pd, Os, Ir, Pt) and of silver: Synthesis, microstructure, and biological action
铂族金属(Ru、Rh、Pd、Os、Ir、Pt)和银的双金属纳米颗粒:合成、微观结构和生物作用
  • 批准号:
    286659497
  • 财政年份:
    2016
  • 资助金额:
    --
  • 项目类别:
    Research Grants
Preparation of a bioactive cochlea implant electrode by electrophoretic deposition of DNA-functionalized nanoparticles
DNA功能化纳米颗粒电泳沉积制备生物活性人工耳蜗电极
  • 批准号:
    328855289
  • 财政年份:
    2016
  • 资助金额:
    --
  • 项目类别:
    Research Grants
Werkstoffe in der Medizin und Pharmazie: Fertigung, Mikrostruktur, Eigenschaften und Anwendung
医学和制药材料:制造、微观结构、性能和应用
  • 批准号:
    261419201
  • 财政年份:
    2014
  • 资助金额:
    --
  • 项目类别:
    Workshops for Early Career Investigators
Synthetic dental composite materials inspired by the hierarchical organization of shark tooth enameloid
受鲨鱼牙釉质分层组织启发的合成牙科复合材料
  • 批准号:
    243494515
  • 财政年份:
    2013
  • 资助金额:
    --
  • 项目类别:
    Priority Programmes
In vivo testing of a genetically active nano-calcium phosphate paste forbone substitution
用于骨替代的基因活性纳米磷酸钙糊剂的体内测试
  • 批准号:
    245867108
  • 财政年份:
    2013
  • 资助金额:
    --
  • 项目类别:
    Research Grants
Therapeutisches Stummschalten von entzündungsrelevanten Genen in intestinalen Epithelzellen durch siRNA-funktionalisierte Calciumphosphat-Nanopartikel
使用 siRNA 功能化磷酸钙纳米粒子治疗性沉默肠上皮细胞中的炎症基因
  • 批准号:
    213786759
  • 财政年份:
    2012
  • 资助金额:
    --
  • 项目类别:
    Research Grants
Laserinduzierte Sub-100 nm-Strukturen zur Erzeugung bioaktiver Nanopartikel-beladener Hydrogele
激光诱导亚 100 nm 结构生成生物活性纳米粒子负载水凝胶
  • 批准号:
    79951137
  • 财政年份:
    2009
  • 资助金额:
    --
  • 项目类别:
    Priority Programmes
Tailored silver nanoparticles (NPs) in biological environments: Interactions with biomolecules and cells (nano.ag)
生物环境中的定制银纳米颗粒 (NP):与生物分子和细胞的相互作用 (nano.ag)
  • 批准号:
    57812932
  • 财政年份:
    2008
  • 资助金额:
    --
  • 项目类别:
    Priority Programmes

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改良HCV多表位基因疫苗及磁性微粒的应用基础研究
  • 批准号:
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  • 批准年份:
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基于量子点多色荧光细胞标志谱型的CTC鉴别与肿瘤个体化诊治的研究
  • 批准号:
    30772507
  • 批准年份:
    2007
  • 资助金额:
    30.0 万元
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    面上项目

相似海外基金

Sustainable and adaptable manufacturing of Gold Nanoparticles for use in Biomedical Diagnostics
用于生物医学诊断的金纳米粒子的可持续和适应性制造
  • 批准号:
    10103609
  • 财政年份:
    2024
  • 资助金额:
    --
  • 项目类别:
    Investment Accelerator
RUI: Developing Predictive Guidelines to Stabilize Gold Nanoparticles with Peptoids
RUI:制定用类肽稳定金纳米粒子的预测指南
  • 批准号:
    2305190
  • 财政年份:
    2023
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    --
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Enhancing immune mediated head and neck cancer anti-tumor activity using nanoparticles
使用纳米粒子增强免疫介导的头颈癌抗肿瘤活性
  • 批准号:
    10747013
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    2023
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    --
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Exploiting the full potential of cancer radiotherapy using a novel combined treatment approach to treat locally advanced tumors
使用新型联合治疗方法充分发挥癌症放射治疗的潜力来治疗局部晚期肿瘤
  • 批准号:
    489006
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    Operating Grants
Development of functional gold nanoparticles for targeted alpha therapy
开发用于靶向α疗法的功能性金纳米颗粒
  • 批准号:
    22KJ2124
  • 财政年份:
    2023
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    --
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Synthesis of 211At-labeled gold nanoparticles for evaluation of anti-tumor activity
211At标记金纳米粒子的合成及其抗肿瘤活性评价
  • 批准号:
    23K06049
  • 财政年份:
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siRNA-based Gold Nanoparticles as a Therapeutic Enhancer for Triple Negative Breast Cancer (TNBC) Radiotherapy
基于 siRNA 的金纳米颗粒作为三阴性乳腺癌 (TNBC) 放射治疗的治疗增强剂
  • 批准号:
    10729127
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Synthesis of monodispersed gold nanoparticles by gas-liquid interfacial plasma reduction using a microfluidic pathway
使用微流体途径通过气液界面等离子体还原合成单分散金纳米颗粒
  • 批准号:
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Development of dynamic hydrogel systems to tune local microenvironement in three dimensional cell culture system
开发动态水凝胶系统来调节三维细胞培养系统中的局部微环境
  • 批准号:
    22F20708
  • 财政年份:
    2022
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A prototype color micro-computed tomography system for imaging gold nanoparticles
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  • 批准号:
    559569-2021
  • 财政年份:
    2022
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  • 项目类别:
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