As a hallmark of solid tumors, hypoxia promotes tumor growth, metastasis, and therapeutic resistance by regulating the expression of hypoxia-related genes. Hypoxia also represents a tumor-specific stimulus that has been exploited for the development of bioreductive prodrugs and advanced drug delivery systems. Cell division cycle 20 (CDC20) functions as an oncogene in tumorigenesis, and we demonstrated the significant upregulation of CDC20 mRNA in the tumor vs paratumor tissues of breast cancer patients and its positive correlation with tumor hypoxia. Herein, a hypoxia-responsive nanoparticle (HRNP) was developed by self-assembly of the 2-nitroimidazole-modified polypeptide and cationic lipid-like compound for delivery of siRNA to specifically target CDC20, a hypoxia-related protumorigenic gene, in breast cancer therapy. The delivery of siCDC20 by HRNPs sufficiently silenced the expression of CDC20 and exhibited potent antitumor efficacy. We expect that this strategy of targeting hypoxia-correlated protumorigenic genes by hypoxia-responsive RNAi nanoparticles may provide a promising approach in cancer therapy.

中文翻译：

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靶向双重低氧的RNAi纳米医学，用于精确的癌症治疗。

作为实体瘤的标志，缺氧通过调节缺氧相关基因的表达来促进肿瘤生长，转移和治疗抗性。缺氧还代表一种肿瘤特异性刺激，已被用于开发生物还原性前药和先进的药物递送系统。细胞分裂周期20（CDC20）在肿瘤发生中起癌基因的作用，我们证明了乳腺癌患者肿瘤组织与癌旁组织中CDC20 mRNA的显着上调及其与肿瘤缺氧的正相关。本文中，通过自组装2-硝基咪唑修饰的多肽和阳离子脂质样化合物开发了一种缺氧响应性纳米颗粒（HRNP），用于在乳腺癌治疗中将siRNA特异性靶向至缺氧相关的致癌基因CDC20。 。HRNP传递siCDC20足以使CDC20的表达沉默，并显示出强大的抗肿瘤功效。我们期望这种通过低氧反应性RNAi纳米粒子靶向与低氧相关的致瘤基因的策略可能在癌症治疗中提供有希望的方法。