Center for RNA Nanobiotechnology and Nanomedicine, College of Pharmacy, James Comprehensive Cancer Center, Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University, Columbus, Ohio, USA.
The Ohio State University Wexner Medical Center, Arthur G. James Comprehensive Cancer Center and Richard J. Solove Institute, Columbus, Ohio, USA.
Nucleic Acid Ther. 2021 Oct;31(5):364-374. doi: 10.1089/nat.2021.0002. Epub 2021 May 17.
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 IC of 20 nmol/kg siRNA encapsulated by exosome particles in the gene knockdown assessment.
肺癌是男性和女性中第二常见的癌症，也是美国癌症死亡的主要原因。非小细胞肺癌（NSCLC）中常用化疗药物耐药性的发展带来了重大的健康风险，因此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 纳米技术在负载小干扰 RNA（siRNA）的外泌体上展示配体，以在动物试验中实现 NSCLC 的消退。胆固醇被用于将针对表皮生长因子受体的配体锚定在负载 siRNA 的外泌体上，以沉默抗凋亡因子生存素。siRNA 的细胞质递送克服了内涵体捕获的问题，导致强效基因敲低、化疗增敏和肿瘤消退，从而在基因敲低评估中实现了 20nmol/kg 被外泌体颗粒包裹的 siRNA 的有利 IC。
