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Rational Design of Tumor Microenvironment-Activated Micelles for Programed Targeting of Breast Cancer Metastasis

机译：肿瘤微环境激活胶束的靶向性靶向乳腺癌转移的合理设计。

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摘要

The poor drug delivery to primary and metastatic tumors of breast cancer remains a great challenge for effective antimetastasis therapy. Herein, a tumor microenvironment-activated cabazitaxel micelles decorated with legumain-specific melittin (TCM-legM) are rationally designed for programed targeting of breast cancer metastasis. TCM-legM is quiescent in blood circulation, but can be specifically activated by the highly expressed legumain in tumor microenvironments to improve their specific targeting and deep penetrating to primary or metastatic tumors. Thereafter, the activated TCM-legM can be efficiently internalized by cancer cells and motivate the rapid pH-responsive drug release for antimetastasis therapy. In metastatic 4T1 breast cancer cells, TCM-legM presents significant inhibition on the proliferation, migration, and invasion activities. In vivo, TCM-legM can be effectively delivered to both primary and metastatic tumors of breast cancer with deep tumor penetration and efficient cellular internalization, thereby resulting in a notable reduction of tumor growth and producing a 93.4% suppression of lung metastasis. Taken together, the rationally designed TCM-legM can provide an intelligent drug delivery strategy to enhance the medical performance on treating breast cancer metastasis.
机译：对于乳腺癌的原发性和转移性肿瘤而言，不良的药物递送仍然是有效的抗转移疗法的巨大挑战。在本文中，合理设计了用豆荚菌素特异性蜂毒蛋白（TCM-legM）装饰的肿瘤微环境激活的卡巴他赛胶束，用于程序化靶向乳腺癌转移。 TCM-legM在血液循环中处于静止状态，但是可以在肿瘤微环境中被高度表达的legumain特异性激活，以改善它们的特异性靶向性并深入穿透原发性或转移性肿瘤。此后，活化的TCM-legM可以被癌细胞有效地内化，并促使快速的pH响应药物释放用于抗转移治疗。在转移性4T1乳腺癌细胞中，TCM-legM对增殖，迁移和侵袭活性具有明显的抑制作用。在体内，TCM-legM可以有效地传递到乳腺癌的原发性和转移性肿瘤中，具有深层的肿瘤穿透力和有效的细胞内在化作用，从而显着降低肿瘤的生长，并抑制93.4％的肺转移。综上所述，合理设计的TCM-legM可以提供一种智能的给药策略，以增强治疗乳腺癌转移的医学性能。

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  • 来源
    《Advanced Functional Materials》 |2018年第8期|1705622.1-1705622.13|共13页
  • 作者

    He Bin; Tan Tao; Wang Hong; Hu Haiyan; Wang Zhiwan; Wang Jing; Li Jie; Sun Kaoxiang; Zhang Zhiwen; Li Yaping;

  • 作者单位

    Chinese Acad Sci, Shanghai Inst Mat Medica, State key Lab Drug Res, Shanghai 201203, Peoples R China;

    Chinese Acad Sci, Shanghai Inst Mat Medica, State key Lab Drug Res, Shanghai 201203, Peoples R China;

    Chinese Acad Sci, Shanghai Inst Mat Medica, State key Lab Drug Res, Shanghai 201203, Peoples R China;

    Yantai Univ, Sch Pharm, Yantai 264005, Shandong, Peoples R China;

    Chinese Acad Sci, Shanghai Inst Mat Medica, State key Lab Drug Res, Shanghai 201203, Peoples R China;

    Yantai Univ, Sch Pharm, Yantai 264005, Shandong, Peoples R China;

    Chinese Acad Sci, Shanghai Inst Mat Medica, State key Lab Drug Res, Shanghai 201203, Peoples R China;

    Yantai Univ, Sch Pharm, Yantai 264005, Shandong, Peoples R China;

    Chinese Acad Sci, Shanghai Inst Mat Medica, State key Lab Drug Res, Shanghai 201203, Peoples R China;

    Chinese Acad Sci, Shanghai Inst Mat Medica, State key Lab Drug Res, Shanghai 201203, Peoples R China;

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  • 原文格式 PDF
  • 正文语种 eng
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  • 关键词

    cabazitaxel; cancer metastasis; micelles; programed targeting; tumor microenvironment;

    机译：卡巴他赛;癌转移;胶束;程序靶向;肿瘤微环境;

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