Lung cancer is the second most common cancer in both men and women and is the leading cause of cancer death in the United States. The development of drug resistance to commonly used chemotherapeutics in non-small-cell lung cancer (NSCLC) poses significant health risks and there is a dire need to improve patient outcomes. In this study, we report the use of RNA nanotechnology to display ligand on exosome that was loaded with small interfering RNA (siRNA) for NSCLC regression in animal trials. Cholesterol was used to anchor the ligand targeting epidermal growth factor receptor on exosomes that were loaded with siRNA to silence the antiapoptotic factor survivin. The cytosolic delivery of siRNA overcame the problem of endosome trapping, leading to potent gene knockdown, chemotherapy sensitization, and tumor regression, thus achieving a favorable IC₅₀ of 20 nmol/kg siRNA encapsulated by exosome particles in the in vivo gene knockdown assessment.

中文翻译：

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通过显示 EGFR RNA 适体的外泌体递送的 siRNA 对非小细胞肺癌的消退

肺癌是男性和女性中第二常见的癌症，并且是美国癌症死亡的主要原因。对非小细胞肺癌 (NSCLC) 中常用化疗药物的耐药性的发展带来了重大的健康风险，迫切需要改善患者的预后。在这项研究中，我们报告了使用 RNA 纳米技术在外泌体上展示配体，该外泌体装载有小干扰 RNA (siRNA)，用于动物试验中的 NSCLC 回归。胆固醇用于将靶向表皮生长因子受体的配体锚定在负载有 siRNA 的外泌体上，以沉默抗凋亡因子生存素。siRNA 的细胞溶质递送克服了内体捕获的问题，导致有效的基因敲低、化疗致敏和肿瘤消退，从而实现了良好的 IC在体内基因敲低评估中， ₅₀个 20 nmol/kg siRNA 被外泌体颗粒包裹。