Rychahou Piotr, Haque Farzin, Shu Yi, Zaytseva Yekaterina, Weiss Heidi L, Lee Eun Y, Mustain William, Valentino Joseph, Guo Peixuan, Evers B Mark
Markey Cancer Center, ‡Department of Surgery, §Pathology and Laboratory Medicine, ∥Nanobiotechnology Center, and ⊥Department of Pharmaceutical Sciences, The University of Kentucky , Lexington, Kentucky 40536, United States.
ACS Nano. 2015 Feb 24;9(2):1108-16. doi: 10.1021/acsnano.5b00067. Epub 2015 Feb 10.
The majority of deaths from all cancers, including colorectal cancer (CRC), is a result of tumor metastasis to distant organs. To date, an effective and safe system capable of exclusively targeting metastatic cancers that have spread to distant organs or lymph nodes does not exist. Here, we constructed multifunctional RNA nanoparticles, derived from the three-way junction (3WJ) of bacteriophage phi29 motor pRNA, to target metastatic cancer cells in a clinically relevant mouse model of CRC metastasis. The RNA nanoparticles demonstrated metastatic tumor homing without accumulation in normal organ tissues surrounding metastatic tumors. The RNA nanoparticles simultaneously targeted CRC cancer cells in major sites of metastasis, such as liver, lymph nodes, and lung. Our results demonstrate the therapeutic potential of these RNA nanoparticles as a delivery system for the treatment of CRC metastasis.
包括结直肠癌(CRC)在内的所有癌症导致的大多数死亡,都是肿瘤转移至远处器官的结果。迄今为止,尚不存在一种能够专门靶向已扩散至远处器官或淋巴结的转移性癌症的有效且安全的系统。在此,我们构建了源自噬菌体phi29马达pRNA的三向接头(3WJ)的多功能RNA纳米颗粒,以在临床相关的CRC转移小鼠模型中靶向转移性癌细胞。这些RNA纳米颗粒显示出转移性肿瘤归巢特性,且不会在转移性肿瘤周围的正常器官组织中蓄积。这些RNA纳米颗粒同时靶向转移的主要部位(如肝脏、淋巴结和肺)中的CRC癌细胞。我们的结果证明了这些RNA纳米颗粒作为治疗CRC转移的递送系统的治疗潜力。