Reshaping Prostate Tumor Microenvironment To Suppress Metastasis via Cancer-Associated Fibroblast Inactivation with Peptide Assembly-Based Nanosystem
Reshaping Prostate Tumor Microenvironment To Suppress Metastasis via Cancer-Associated Fibroblast Inactivation with Peptide Assembly-Based Nanosystem
复制标题
基于肽组装的纳米系统通过癌症相关成纤维细胞灭活重塑前列腺肿瘤微环境以抑制转移
DOI：
10.1021/acsnano.9b04857
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发表时间：
2019-11-01
期刊：
影响因子：
17.1
通讯作者：
Nie, Guangjun
中科院分区：
文献类型：
--
作者：
Lang, Jiayan;Zhao, Xiao;Nie, Guangjun
前列腺癌是男性最常见的恶性肿瘤之一，抑制转移是前列腺癌治疗中的关键事件，但仍是一大挑战。肿瘤相关成纤维细胞(CAF)通过塑造恶性肿瘤微环境，在前列腺癌转移中发挥重要作用。在此，我们通过将成纤维细胞激活蛋白-α(FAP-α)抗体负载到基于细胞穿透肽(CPP)的纳米颗粒上，构建了CAF靶向siRNA递送系统，该纳米颗粒特异性地下调了CAF中C-X-C基序趋化因子配体12(CXCL12)的表达。这种调节通过灭活CAF产生了一系列的变化，从而重塑了前列腺癌的恶性微环境。肿瘤细胞的侵袭、迁移和肿瘤血管生成受到明显抑制，这都有助于抑制原位前列腺癌的转移。这种通过CAF靶向和失活来重塑肿瘤微环境的策略为抑制前列腺癌的恶性转移提供了一种替代方法。
Prostate cancer is one of the most common malignant tumors in men, and inhibiting metastasis is a key event but still a major challenge in prostate cancer treatment. Cancer-associated fibroblasts (CAFs) play an important role in prostate tumor metastasis by shaping the malignant tumor microenvironment. Herein, we constructed a CAF-targeting siRNA delivery system by loading the fibroblast activation protein-alpha (FAP-alpha) antibody onto the cell-penetrating peptide (CPP)-based nanoparticles, which specifically downregulated C-X-C motif chemokine ligand 12 (CXCL12) expression in CAFs. This regulation generated a series of changes through inactivating CAFs so that the malignant prostate tumor microenvironment was reshaped. The tumor cell invasion, migration, and tumor angiogenesis were significantly inhibited, which all contributed to the suppression of the metastasis of an orthotopic prostate tumor. This tumor microenvironment reshaping strategy via CAF targeting and inactivation provides an alternative approach for malignant prostate tumor metastasis inhibition.