Food Laboratory of Zhongyuan, Key Laboratory of Precision Nutrition and Food Quality, Department of Nutrition and Health, China Agricultural University, No. 17 Qinghua Donglu, Beijing, 100083, China.
College of Veterinary Medicine, China Agricultural University, Beijing, 100094, China.
J Nanobiotechnology. 2023 Jun 7;21(1):182. doi: 10.1186/s12951-023-01941-z.
Due to its complicated pathophysiology, propensity for metastasis, and poor prognosis, colon cancer is challenging to treat and must be managed with a combination of therapy. Using rolling circle transcription (RCT), this work created a nanosponge therapeutic medication system (AS1411@antimiR-21@Dox). Using the AS1411 aptamer, this approach accomplished targeted delivery to cancer cells. Furthermore, analysis of cell viability, cell apoptosis, cell cycle arrest, reactive oxygen species (ROS) content, and mitochondrial membrane potential (MMP) levels revealed that functional nucleic acid nanosponge drug (FND) can kill cancer cells. Moreover, transcriptomics uncovered a putative mechanism for the FND anti-tumor effect. These pathways, which included mitotic metaphase and anaphase as well as the SMAC-mediated dissociation of the IAP: caspase complexes, were principally linked to the cell cycle and cell death. In conclusion, by triggering cell cycle arrest and apoptosis, the nano-synergistic therapeutic system allowed for the intelligent and effective targeted administration of RNA and chemotherapeutic medicines for colon cancer treatment. The system allowed for payload efficiency while being customizable, targeted, reliable, stable, and affordable.
由于其复杂的病理生理学、转移倾向和预后不良，结肠癌的治疗具有挑战性，必须结合多种疗法进行管理。本研究采用滚环转录（RCT）技术构建了一种纳米海绵治疗药物系统（AS1411@antimiR-21@Dox）。该方法利用 AS1411 适体实现了对癌细胞的靶向递送。此外，细胞活力、细胞凋亡、细胞周期停滞、活性氧（ROS）含量和线粒体膜电位（MMP）水平的分析表明，功能核酸纳米海绵药物（FND）可以杀死癌细胞。此外，转录组学揭示了 FND 抗肿瘤作用的一种可能机制。这些途径主要与细胞周期和细胞死亡有关，包括有丝分裂中期和后期以及 SMAC 介导的 IAP：半胱天冬酶复合物解离。总之，通过触发细胞周期停滞和细胞凋亡，纳米协同治疗系统实现了 RNA 和化疗药物的智能、有效靶向给药，用于结肠癌的治疗。该系统具有高效载药能力，同时具有定制化、靶向性、可靠性、稳定性和经济性。
