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首页> 外文期刊>Nano letters >Spatial Targeting of Tumor-Associated Macrophages and Tumor Cells with a pH-Sensitive Cluster Nanocarrier for Cancer Chemoimmunotherapy
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Spatial Targeting of Tumor-Associated Macrophages and Tumor Cells with a pH-Sensitive Cluster Nanocarrier for Cancer Chemoimmunotherapy

机译：肿瘤相关巨噬细胞和肿瘤细胞的空间靶向癌细胞瘤癌细胞癌

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摘要

Chemoimmunotherapy, which combines chemotherapeutics with immune-modulating agents, represents an appealing approach for improving cancer therapy. To optimize its therapeutic efficacy, differentially delivering multiple therapeutic drugs to target cells is desirable. Here we developed an immunostimulatory nanocarrier (denoted as BLz-945SCNS/Pt) that could spatially target tumor-associated macrophages (TAMs) and tumor cells for cancer chemoimmunotherapy. (BLz-945)SCNs/Pt undergo supersensitive structure collapse in the prevascular regions of tumor tissues and enable the simultaneous release of platinum (Pt)-prodrug conjugated small particles and (BLz-945), a small molecule inhibitor of colony stimulating-, factor 1 receptor (CSF-1R) of TAMs. The released BLZ-945 can be preferentially taken up by TAMs to cause TAMs depletion from tumor tissues, while the small particles carrying Pt-prodrug enable deep tumor penetration as well as intracellularly specific drug release to kill more cancer cells. Our studies demonstrate that (BLz-945)SCNs/Pt outperform their monotherapy counterparts in multiple tumor models. The underlying mechanism studies suggest that the designer pH-sensitive codelivery nanocarrier not only induces apoptosis of tumor cells but also modulates the tumor immune environment to eventually augment the antitumor effect of CD8+ cytotoxic T cells through TAMs depletion.
机译：将化学治疗剂与免疫调节剂结合的化疗疗法代表了改善癌症治疗的吸引力方法。为了优化其治疗效果，差异地将多种治疗药物递送给靶细胞。在这里，我们开发了一种免疫刺激性纳米载体（表示为BLZ-945SCNS / PT），其可以在空间上靶向肿瘤相关的巨噬细胞（TAMS）和肿瘤细胞用于癌症化疗疗法。 （BLZ-945）SCNS / PT在肿瘤组织的血管内区域进行过敏结构塌陷，并使铂（PT） - 预保温缀合的小颗粒和（BLZ-945）的同时释放，殖民地刺激的小分子抑制剂 - ， TAMS的因子1受体（CSF-1R）。释放的BLZ-945可以优先由TAMS占用，以使TAMS从肿瘤组织中耗尽，而携带PT-Prodrug的小颗粒使得细胞瘤渗透以及细胞内特异性药物释放以杀死更多的癌细胞。我们的研究表明（BLZ-945）SCNS / PT在多种肿瘤模型中优于它们的单药治疗。潜在的机制研究表明，设计者pH敏感的编码纳米载体不仅诱导肿瘤细胞的凋亡，还诱导肿瘤免疫环境，最终通过TAMS耗尽来增强CD8 +细胞毒性T细胞的抗肿瘤效应。

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