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首页> 外文期刊>Biomaterials Science >CD133 peptide-conjugated pyropheophorbide-a as a novel photosensitizer for targeted photodynamic therapy in colorectal cancer stem cells
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CD133 peptide-conjugated pyropheophorbide-a as a novel photosensitizer for targeted photodynamic therapy in colorectal cancer stem cells

机译：CD133肽 - 缀合的焦泡泡酰亚胺-A作为结直肠癌干细胞靶向光动力疗法的新型光敏剂

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摘要

Colorectal cancer (CRC) is the third most common cancer around the world. Recent findings suggest that cancer stem cells (CSCs) play a pivotal role in the resistance to current therapeutic modalities, including surgery and chemotherapy. Photodynamic therapy (PDT) is a promising non-invasive therapeutic strategy for advanced metastatic CRC. Traditional photosensitizers such as pyropheophorbide-a (Pyro) lack tumor selectivity, causing unwanted treatment-related toxicity to the surrounding normal tissue. In order to enhance the targeting properties of Pyro, we synthesize a novel photosensitizer, CD133-Pyro, via the conjugation of Pyro to a peptide domain targeting CD133, which is highly expressed on CRC CSCs and correlated with poor prognosis of CRC patients. We demonstrate that CD133 Pyro possesses the targeted delivery capacity both in CRC CSCs derived from HT29 and SW620 cell lines and in a xenograft mouse model of tumor growth. CD133 Pyro PDT can promote the production of reactive oxygen species (ROS), suppress the sternness properties, and induce autophagic cell death in CRC CSCs. Furthermore, CD133-Pyro PDT has a potent inhibitory effect on CRC CSC-derived xenograft tumors in nude mice. These findings may offer a useful and important strategy for the treatment of CRC through targeting CSCs.
机译：结肠直肠癌（CRC）是世界各地的第三次常见的癌症。最近的发现表明，癌症干细胞（CSCs）在对当前治疗方式的抵抗力中起着枢轴作用，包括手术和化疗。光动力治疗（PDT）是前期转移CRC的有希望的非侵入性治疗策略。传统光敏剂如纤维黄酚-A（热量）缺乏肿瘤选择性，导致对周围正常组织的不希望的治疗相关的毒性。为了增强Pyro的靶向性质，我们通过用Pyro缀合到靶向CD133的肽结构域的靶向光敏剂CD133-PERO，这在CRC CSC上高度表达并与CRC患者的预后不良相关。我们证明了CD133的PYRO具有来自HT29和SW620细胞系的CRC CSC的靶向递送能力，以及肿瘤生长的异种移植小鼠模型。 CD133热量PDT可以促进反应性氧物质（ROS）的生产，抑制沉默性质，并在CRC CSC中诱导自噬细胞死亡。此外，CD133-PYRO PDT对裸鼠CRC CSC衍生的异种移植肿瘤具有有效的抑制作用。这些发现可以通过靶向CSC来提供对CRC的有用和重要策略。

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  • 来源
    《Biomaterials Science》 |2021年第6期|共12页
  • 作者

    Yan Shichao; Tang Da; Hong Zhangyong; Wang Jing; Yao Hui; Lu Lu; Yi Huimei; Fu Shujun; Zheng Chanjuan; He Guangchun; Zou Heng; Hou Xuyang; He Qing; Xiong Li; Li Qinglong; Deng Xiyun;

  • 作者单位

    Cent South Univ Xiangya Hosp 2 Dept Gen Surg Changsha 410011 Hunan Peoples R China;

    Cent South Univ Xiangya Hosp 3 Dept Gen Surg Changsha 410013 Hunan Peoples R China;

    Nankai Univ Coll Life Sci State Key Lab Med Chem Biol Tianjin Key Lab Prot Sci Tianjin 300071 Peoples R China;

    Nankai Univ Coll Life Sci State Key Lab Med Chem Biol Tianjin Key Lab Prot Sci Tianjin 300071 Peoples R China;

    Hunan Normal Univ Key Lab Translat Canc Stem Cell Res Changsha 410013 Hunan Peoples R China;

    Hunan Normal Univ Key Lab Translat Canc Stem Cell Res Changsha 410013 Hunan Peoples R China;

    Hunan Normal Univ Key Lab Translat Canc Stem Cell Res Changsha 410013 Hunan Peoples R China;

    Hunan Normal Univ Key Lab Translat Canc Stem Cell Res Changsha 410013 Hunan Peoples R China;

    Hunan Normal Univ Key Lab Translat Canc Stem Cell Res Changsha 410013 Hunan Peoples R China;

    Hunan Normal Univ Key Lab Translat Canc Stem Cell Res Changsha 410013 Hunan Peoples R China;

    Cent South Univ Xiangya Hosp 2 Dept Gen Surg Changsha 410011 Hunan Peoples R China;

    Cent South Univ Xiangya Hosp 2 Dept Gen Surg Changsha 410011 Hunan Peoples R China;

    Cent South Univ Xiangya Hosp 2 Dept Gen Surg Changsha 410011 Hunan Peoples R China;

    Cent South Univ Xiangya Hosp 2 Dept Gen Surg Changsha 410011 Hunan Peoples R China;

    Cent South Univ Xiangya Hosp 2 Dept Gen Surg Changsha 410011 Hunan Peoples R China;

    Hunan Normal Univ Key Lab Translat Canc Stem Cell Res Changsha 410013 Hunan Peoples R China;

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  • 正文语种 eng
  • 中图分类 分子生物学;
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