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首页> 外文期刊>Biomaterials Science >Development of EGFR-targeted evodiamine nanoparticles for the treatment of colorectal cancer
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Development of EGFR-targeted evodiamine nanoparticles for the treatment of colorectal cancer

机译：EGFR靶向Evodiamine纳米粒子的开发用于治疗结直肠癌

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摘要

Invasion and metastasis of colorectal cancer (CRC) are leading causes of death of CRC patients. Previous findings demonstrate that evodiamine (Evo), an indolequinone alkaloid, is effective in combating CRC; however, its poor aqueous solubility and low oral bioavailability limit its application in the prevention of invasion and metastasis of CRC. It is known that selectively targeting cancer-specific receptors highly expressed on the surface of cancer cells by nanocarriers loaded with cytotoxic drugs is a viable strategy in nanobiotechnology to enhance cancer cell killing and minimize side effects. In this study, we report the development of a new class of nanotherapeutics: EGFR-targeting Evo-encapsulated poly(amino acid) nanoparticles (GE11-Evo-NPs). These nanoparticles exhibited good aqueous solubility, slow release, and active targeting capability. Their inhibitory effect on human colon cancer cells and therapeutic efficacy against invasion and metastasis of CRC in nude mice were systematically investigated. Mechanisms of the GE11-Evo-NPs against EGFR mediated invasion and metastasis of CRC were also explored. Compared with free Evo, the GE11-Evo-NPs showed significantly increased cytotoxicity to colon cancer cells and potently inhibited CRC LoVo cell adhesion, invasion, and migration. The expression of EGFR, VEGF, and MMP proteins was dramatically down-regulated, which may partially account for their inhibition of invasion and metastasis of CRC. Moreover, in vivo studies show that the GE11-Evo-NPs exhibited much greater potency than other control groups in inhibiting CRC invasion and metastasis, tumor volume, and growth in nude mice, leading to a significantly prolonged tumor-bearing survival duration (P < 0.01).
机译：结肠直肠癌（CRC）的侵袭和转移是CRC患者死亡的主要原因。以前的研究结果表明，Evodiamine（EVO），一种吲哚醌生物碱，有效地对抗CRC;然而，其差的水溶性和低口服生物利用度限制了其在预防CRC的侵袭和转移方面的应用。众所周知，通过纳米载体用细胞毒性药物的纳米载体选择性地靶向癌细胞表面高度表达的癌症特异性受体是纳米生物技术的可行策略，以增强癌细胞杀伤并最小化副作用。在这项研究中，我们报告了一类新纳米治疗方法的发展：EGFR靶向EVO封装的聚（氨基酸）纳米颗粒（GE11-EVO-NPS）。这些纳米颗粒表现出良好的含水溶解度，缓慢释放和活性靶向能力。系统地研究了对人性结肠癌细胞的抑制作用和裸鼠中CRC的侵袭和转移的治疗效果。还探讨了GE11-EVO-NPS对EGFR介导的入侵和CRC转移的机制。与免费EVO相比，GE11-EVO-NPS显示出对结肠癌细胞的细胞毒性显着增加，并且具有效果抑制CRC Lovo细胞粘附，侵袭和迁移。 EGFR，VEGF和MMP蛋白的表达显着下调，这可能部分地抑制CRC的侵袭和转移。此外，在体内研究表明，GE11-EVO-NPS表现出比抑制CRC侵袭和转移，裸鼠的转移，肿瘤体积，肿瘤体积和生长的其他对照组更大的效力，导致显着延长的肿瘤存活时间（P < 0.01）。

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  • 来源
    《Biomaterials Science》 |2019年第9期|共13页
  • 作者

    Li Chunpu; Cai Gang; Song Daqian; Gao Ruixuan; Teng Peng; Zhou LiHong; Ji Qing; Sui Hua; Cai Jianfeng; Li Qi; Wang Yan;

  • 作者单位

    Shanghai Univ Tradit Chinese Med Acad Integrat Med Shuguang Hosp Dept Med Oncol Shanghai 201203 Peoples R China;

    Shanghai Univ Tradit Chinese Med Acad Integrat Med Shuguang Hosp Dept Med Oncol Shanghai 201203 Peoples R China;

    Shanghai Univ Tradit Chinese Med Acad Integrat Med Shuguang Hosp Dept Med Oncol Shanghai 201203 Peoples R China;

    Univ S Florida Dept Chem 4202 E Fowler Ave Tampa FL 33620 USA;

    Univ S Florida Dept Chem 4202 E Fowler Ave Tampa FL 33620 USA;

    Shanghai Univ Tradit Chinese Med Acad Integrat Med Shuguang Hosp Dept Med Oncol Shanghai 201203 Peoples R China;

    Shanghai Univ Tradit Chinese Med Acad Integrat Med Shuguang Hosp Dept Med Oncol Shanghai 201203 Peoples R China;

    Shanghai Univ Tradit Chinese Med Acad Integrat Med Shuguang Hosp Dept Med Oncol Shanghai 201203 Peoples R China;

    Univ S Florida Dept Chem 4202 E Fowler Ave Tampa FL 33620 USA;

    Shanghai Univ Tradit Chinese Med Acad Integrat Med Shuguang Hosp Dept Med Oncol Shanghai 201203 Peoples R China;

    Shanghai Univ Tradit Chinese Med Acad Integrat Med Shuguang Hosp Dept Med Oncol Shanghai 201203 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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