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首页> 外文期刊>Journal of Controlled Release: Official Journal of the Controlled Release Society >Selectively targeting tumor-associated macrophages and tumor cells with polymeric micelles for enhanced cancer chemo-immunotherapy
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Selectively targeting tumor-associated macrophages and tumor cells with polymeric micelles for enhanced cancer chemo-immunotherapy

机译：用聚合物胶束选择性靶向肿瘤相关的巨噬细胞和肿瘤细胞，用于增强癌症化疗 - 免疫疗法

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摘要

Tumor-associated macrophage (TAM)-related immunotherapy is a greatly promising strategy that involves altering the immunosuppressive tumor microenvironment with the immunomodulator imiquimod (R837) for enhanced cancer therapy. However, the function of R837 is seriously limited due to poor water solubility and a lack of targeting ability. Here, we developed two types of targeting polymer micelles to separately deliver R837 and the anticancer drug doxorubicin (DOX) to TAMs and tumor cells via intratumoral injection and intravenous injection, respectively, for enhanced cancer chemo-immunotherapy against breast cancer. After these micelles accumulated in the tumor tissues, the immunostimulating micelles released R837, which bound to the TLR-7 receptor on the lysosomal membrane within the TAM, stimulating the maturation of the TAM, thereby causing an antitumor immune response and relieving the immunosuppressive effect in the tumor microenvironment. Simultaneously, the chemotherapeutic micelles released DOX in the cytoplasm of the tumor cells, directly inducing cell death. As a result, a synergistic combination of chemotherapy and immunotherapy was achieved through these nanomedicines, which separately activated the antitumor immune response and inhibited tumor cell growth. Therefore, this strategy is a new avenue for the development of targeting nanomedicines for combination chemo-immunotherapy against malignant cancer.
机译：肿瘤相关的巨噬细胞（TAM） - 相关的免疫疗法是一种非常有希望的策略，涉及将免疫抑制肿瘤微环境与免疫调节剂咪唑（R837）改变以提高癌症治疗。然而，由于水溶解度差和缺乏靶向能力，R837的功能受到严重限制。在这里，我们开发了两种类型的靶向聚合物胶束，可分别通过肿瘤内注射和静脉注射分别为TAMS和肿瘤细胞分别递送R837和抗癌药物，用于增强癌症化学免疫治疗乳腺癌。在这些胶束累积在肿瘤组织中，免疫刺激胶束释放的R837，其与TLR-7受体结合在TAM内的溶酶体膜中，刺激TAM的成熟，从而导致抗肿瘤免疫应答并减轻免疫抑制作用肿瘤微环境。同时，化学治疗胶束在肿瘤细胞的细胞质中释放了DOX，直接诱导细胞死亡。结果，通过这些纳米次氨酸实现化疗和免疫疗法的协同组合，其分别激活抗肿瘤免疫应答并抑制肿瘤细胞生长。因此，该策略是开发靶向纳米胺的新途径，用于对恶性癌症进行化学免疫治疗。

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  • 作者

    Wei Xiao; Liu Lingqiao; Li Xilin; Wang Yi; Guo Xing; Zhao Jingya; Zhou Shaobing;

  • 作者单位

    Southwest Jiaotong Univ Sch Mat Sci &

    Engn Key Lab Adv Technol Mat Minist Educ Chengdu 610031 Sichuan Peoples R China;

    Southwest Jiaotong Univ Sch Mat Sci &

    Engn Key Lab Adv Technol Mat Minist Educ Chengdu 610031 Sichuan Peoples R China;

    Southwest Jiaotong Univ Sch Mat Sci &

    Engn Key Lab Adv Technol Mat Minist Educ Chengdu 610031 Sichuan Peoples R China;

    Southwest Jiaotong Univ Sch Mat Sci &

    Engn Key Lab Adv Technol Mat Minist Educ Chengdu 610031 Sichuan Peoples R China;

    Southwest Jiaotong Univ Sch Mat Sci &

    Engn Key Lab Adv Technol Mat Minist Educ Chengdu 610031 Sichuan Peoples R China;

    Southwest Jiaotong Univ Sch Mat Sci &

    Engn Key Lab Adv Technol Mat Minist Educ Chengdu 610031 Sichuan Peoples R China;

    Southwest Jiaotong Univ Sch Mat Sci &

    Engn Key Lab Adv Technol Mat Minist Educ Chengdu 610031 Sichuan Peoples R China;

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

    Tumor-associated macrophage; Immune response; Chemo-immunotherapy; Targeting; Micelles;

    机译：肿瘤相关的巨噬细胞;免疫应答;化学免疫疗法;靶向;胶束;

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