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紫杉醇联合 MicroRNA-125b 重极化肿瘤相关巨噬细胞增强上皮性卵巢癌的抗肿瘤疗效。

Improved anti-tumor efficacy of paclitaxel in combination with MicroRNA-125b-based tumor-associated macrophage repolarization in epithelial ovarian cancer.

机构信息

Department of Pharmaceutical Sciences, School of Pharmacy, Boston, MA, 02115, USA.

Department of Pharmaceutical Sciences, School of Pharmacy, Boston, MA, 02115, USA; Department of Chemical Engineering, College of Engineering, Northeastern University, Boston, MA, 02115, USA.

出版信息

Cancer Lett. 2019 Oct 1;461:1-9. doi: 10.1016/j.canlet.2019.07.002. Epub 2019 Jul 6.

Abstract

In epithelial ovarian cancers, the presence of tumor-associated macrophages (TAMs) is well correlated with the poor disease outcomes. TAMs are know to suppress the immune system, induce pro-tumoral functions and inhibit anti-tumor responses associated with chemotherapy. In this study, we have evaluated the synergistic efficacy of TAM repolarization and intraperitoneal paclitaxel in epithelial ovarian cancers. We demonstrate that hyaluronic acid-based nanoparticles encapsulating miR-125b (HA-PEI-miR-125b) can specifically target TAMs in the peritoneal cavity of a syngeneic ID8-VEGF ovarian cancer mouse model and can repolarize macrophages to an immune-activating phenotype. These HA-PEI-miR-125b nanoparticles in combination with intraperitoneal paclitaxel can enhance the anti-tumor efficacy of paclitaxel during the later stages of disease progression as seen by the significant reduction in the ascitic fluid and peritoneal VEGF levels. Furthermore, these HA-PEI-miR-125b nanoparticles do not induce systemic toxicity and thus warrant a further evaluation in the clinical setting.

摘要

在卵巢上皮癌中,肿瘤相关巨噬细胞(TAMs)的存在与不良预后密切相关。已知 TAMs 抑制免疫系统,诱导促肿瘤功能,并抑制与化疗相关的抗肿瘤反应。在这项研究中,我们评估了 TAM 重极化和腹腔内紫杉醇在卵巢上皮癌中的协同疗效。我们证明,基于透明质酸的纳米粒子包封 miR-125b(HA-PEI-miR-125b)可以特异性靶向同基因 ID8-VEGF 卵巢癌小鼠模型腹腔中的 TAMs,并将巨噬细胞重极化为免疫激活表型。这些 HA-PEI-miR-125b 纳米粒子与腹腔内紫杉醇联合使用可以增强紫杉醇在疾病进展后期的抗肿瘤疗效,因为腹水和腹腔 VEGF 水平显著降低。此外,这些 HA-PEI-miR-125b 纳米粒子不会引起全身毒性,因此值得在临床环境中进一步评估。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5121/6682447/970026962224/nihms-1534606-f0001.jpg

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本文引用的文献

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Tumour-associated macrophages as treatment targets in oncology.肿瘤相关巨噬细胞作为肿瘤治疗的靶点。
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