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Design of peptide-conjugated glycol chitosan nanoparticles for near infrared fluorescent (NIRF) in vivo imaging of bladder tumors

机译:肽共轭乙二醇壳聚糖纳米粒子在膀胱肿瘤体内成像中的应用

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摘要

Enhanced permeability and retention (EPR) effects for tumor treatment have been utilized as a representative strategy to accumulate untargeted nanoparticles in the blood vessels around tumors. However, the EPR effect itself was not sufficient for the nanoparticles to penetrate into cancer cells. For the improvement of diagnosis and treatment of cancer using nanoparticles, many more nanoparticles need to specifically enter cancer cells. Otherwise, can leave the tumor area and not contribute to treatment. In order to enhance the internalization process, specific ligands on nanoparticles can help their specific internalization in cancer cells by receptor-mediated endocytosis. We previously developed glycol chitosan based nanoparticles that suggested a promising possibility for in vivo tumor imaging using the EPR effect. The glycol chitosan nanoparticles showed a long circulation time beyond 1 day and they were accumulated predominantly in tumor. In this study, we evaluated two peptides for specific targeting and better internalization into urinary bladder cancer cells. We conjugated the peptides on to the glycol chitosan nanoparticles; the peptide-conjugated nanoparticles were also labeling with near infrared fluorescent (NIRF) dye, Cy5.5, to visualize them by optical imaging in vivo. Importantly real-time NIRF imaging can also be used for fluorescence (NIRF)-guided surgery of tumors beyond normal optical penetration depths. The peptide conjugated glycol chitosan nanoparticles were characterized with respect to size, stability and zeta-potential and compared with previous nanoparticles without ligands in terms of their internalization into bladder cancer cells. This study demonstrated the possibility of our nanoparticles for tumor imaging and emphasized the importance of specific targeting peptides.
机译:用于肿瘤治疗的增强的渗透性和保留(EPR)效应已被用作代表策略,以在肿瘤周围的血管中积累未靶向的纳米颗粒。但是,EPR效应本身不足以使纳米粒子渗透到癌细胞中。为了使用纳米颗粒改善癌症的诊断和治疗,需要更多的纳米颗粒特异性地进入癌细胞。否则,会离开肿瘤区域而无助于治疗。为了增强内在化过程,纳米粒子上的特异性配体可以通过受体介导的内吞作用帮助其在癌细胞中进行特异性内化。我们之前开发了基于乙二醇壳聚糖的纳米颗粒,这表明使用EPR效应进行体内肿瘤成像的可能性很大。乙二醇壳聚糖纳米颗粒的循环时间超过1天,并且主要聚集在肿瘤中。在这项研究中,我们评估了两种肽的特异性靶向作用和更好地内化到膀胱癌细胞中。我们将肽缀合到乙二醇壳聚糖纳米颗粒上。还用近红外荧光(NIRF)染料Cy5.5标记了肽偶联的纳米颗粒,以通过体内光学成像将其可视化。重要的是,实时NIRF成像还可用于荧光(NIRF)指导的超出正常光学穿透深度的肿瘤手术。肽缀合的乙二醇壳聚糖纳米颗粒的尺寸,稳定性和Zeta电位均经过表征,并与以前没有配体的纳米颗粒相比,它们的内在化作用使其进入膀胱癌细胞。这项研究证明了我们的纳米颗粒用于肿瘤成像的可能性,并强调了特异性靶向肽的重要性。

著录项

  • 来源
  • 会议地点 San Francisco CA(US)
  • 作者单位

    Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN Birck Nanotechnology Center at Discovery Park, Purdue University, West Lafayette, IN Bindley Bioscience Center at Discovery Park, Purdue University, West Lafayette, IN;

    School of Veterinary Medicine-Department of Basic Medical Sciences, Purdue University, West Lafayette, IN;

    School of Veterinary Medicine-Department of Basic Medical Sciences, Purdue University, West Lafayette, IN;

    Biomedical Research Center, Korea Institute of Science and Technology, Seoul, Korea;

    Biomedical Research Center, Korea Institute of Science and Technology, Seoul, Korea;

    Biomedical Research Center, Korea Institute of Science and Technology, Seoul, Korea;

    Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN Birck Nanotechnology Center at Discovery Park, Purdue University, West Lafayette, IN Bindley Bioscience Center at Discovery Park, Purdue University, West Lafayette, IN School of Veterinary Medicine-Department of Basic Medical Sciences, Purdue University, West Lafayette, IN;

  • 会议组织
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 医用物理学;
  • 关键词

    bladder; tumor; peptide; glycol chitosan; nanoparticle; near infrared fluorescence imaging;

    机译:膀胱;瘤;肽乙二醇壳聚糖纳米粒子近红外荧光成像;

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