Lung cancer is the leading cause of cancer death in the United States. Here we report the utilization of the special rubber- and amoeba-like property of RNA nanoparticles to deliver two kinds of anticancer drugs for highly efficient regression of lung cancer. Conjugation of the chemical drugs to RNA nanoparticle enhance the solubility of the drug by 32,000-fold. 5% of the RNA/drug complexes reached the tumor within 30 minutes after systemic injection, and those that did not reach the tumor were excreted from the kidney and found in urine 30 minutes after IV injection. RNA nanoparticles loaded with drugs significantly inhibited the tumor growth in the A549 xenograft mouse model without the need for targeting ligand. This could be explained by several factors, such as the deformative property, the longer circulation time, the passive accumulation, and the quick renal excretion time of the RNA/drug complex.

Citation Format: Xin Li, Satheesh Ellipilli, Hongzhi Wang, Wen-Jui Lee, Yuan Soon Ho, Peixuan Guo. Rubber- and amoeba-like RNA nanoparticles facilitate drug delivery for lung cancer [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2021 Oct 7-10. Philadelphia (PA): AACR; Mol Cancer Ther 2021;20(12 Suppl):Abstract nr P172.