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首页> 外文期刊>Molecular pharmaceutics >cRGD Peptide-Conjugated Pyropheophorbide-a Photosensitizers for Tumor Targeting in Photodynamic Therapy
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cRGD Peptide-Conjugated Pyropheophorbide-a Photosensitizers for Tumor Targeting in Photodynamic Therapy

机译：CRGD肽 - 缀合的纤维黄酚 - 用于靶向光动力治疗中的肿瘤的光敏剂

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摘要

Pyropheophorbide-a (Pyro) is a highly promising photosensitizer for tumor photodynamic therapy (PDT), although its very limited tumor-accumulation ability seriously restricts its clinical applications. A higher accumulation of photosensitizers is very important for the treatment of deeply seated and larger tumors. The conjugation of Pyro with tumor-homing peptide ligands could be a very useful strategy to optimize the physical properties of Pyro. Herein, we reported our studies on the conjugation of Pyro with a cyclic cRGDfK (cRGD) peptide, an integrin binding sequence, to develop highly tumor-specific photosensitizers for PDT application. To further reduce the nonspecific uptake and, thus, reduce the background distribution of the conjugates in normal tissues, we opted to add a highly hydrophilic polyethylene glycol (PEG) chain and an extra strongly hydrophilic carboxylic acid group as the linker to avoid the direct connection of the strongly hydrophobic Pyro macrocycle and cRGD ligand. We reported here the synthesis and characterization of these conjugates, and the influence of the hydrophilic modification on the biological function of the conjugates was carefully studied. The tumor-accumulation ability and photodynamic-induced cell-killing ability of these conjugates were evaluated through both in vitro cell-based experiment and in vivo distribution and tumor therapy experiments with tumor-bearing mice. Thus, the synthesized conjugate significantly improved the tumor enrichment and tumor selectivity of Pyro, as well as abolished the xenograft tumors in the murine model through a one-time PDT treatment.
机译：纤维黄酚-A（烙棉）是一种高度有前景的光敏剂，用于肿瘤光动力治疗（PDT），但其非常有限的肿瘤积累能力严重限制其临床应用。对光敏剂的较高积累对于治疗深深坐着和较大的肿瘤非常重要。用肿瘤归巢肽配体的缀合物是一种非常有用的策略，以优化Pyro的物理性质。在此，我们向循环CRGDFK（CRGD）肽，整联蛋白结合序列缀合的研究报告了PYRO的缀合，用于为PDT施用开发高度肿瘤特异性光敏剂。为了进一步降低非特异性摄取，从而减少正常组织中缀合物的背景分布，我们选择加入高度亲水的聚乙二醇（PEG）链和超强亲水的羧酸基团作为接头，以避免直接连接强烈疏水的热致癌和CRGD配体。我们在此报道了这些缀合物的合成和表征，以及亲水改性对缀合物的生物功能的影响。通过基于体外细胞的实验和具有肿瘤携带小鼠的体内分布和肿瘤治疗实验，评估这些缀合物的肿瘤累积能力和光动力诱导的细胞杀伤能力。因此，合成的缀合物显着改善了肿瘤的富集和肿瘤选择性，并通过一次性PDT处理废除了小鼠模型中的异种移植肿瘤。

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  • 来源
    《Molecular pharmaceutics》 |2018年第4期|共10页
  • 作者

    Wenjing Li; Sihai Tan; Yutong Xing; Qian Liu; Shuang Li; Qingle Chen; Min Yu; Fengwei Wang; Zhangyong Hong;

  • 作者单位

    State Key Laboratory of Medicinal Chemical Biology Tianjin Key Laboratory of Protein Sciences;

    Tianjin University of Traditional Chinese Medicine Tianjin 300193 P. R. China;

    State Key Laboratory of Medicinal Chemical Biology Tianjin Key Laboratory of Protein Sciences;

    State Key Laboratory of Medicinal Chemical Biology Tianjin Key Laboratory of Protein Sciences;

    State Key Laboratory of Medicinal Chemical Biology Tianjin Key Laboratory of Protein Sciences;

    State Key Laboratory of Medicinal Chemical Biology Tianjin Key Laboratory of Protein Sciences;

    Department of Gynecologic Oncology Tianjin Medical University Cancer Institute and Hospital;

    People’s Hospital of Tianjin Tianjin 300180 P. R. China;

    State Key Laboratory of Medicinal Chemical Biology Tianjin Key Laboratory of Protein Sciences;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 药学;
  • 关键词

    integrin; peptide conjugate; photodynamic therapy; photosensitizer; pyropheophorbide-a;

    机译：整合蛋白;肽缀合物;光动力疗法;光敏剂;热酚 - a;

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