A triple-combination nanotechnology platform based on multifunctional RNA hydrogel for lung cancer therapy

作     者：Junwei Li Dandan Yuan Xiangjiang Zheng Xinyue Zhang Xuemei Li Shusheng Zhang Junwei Li;Dandan Yuan;Xiangjiang Zheng;Xinyue Zhang;Xuemei Li;Shusheng Zhang

作者机构：Collaborative Innovation Center of Tumor Marker Detection TechnologyEquipment and Diagnosis-Therapy Integration in Universities of ShandongShandong Province Key Laboratoty of Detection Technology for Tumor MakersSchool of Chemistry and Chemical EngineeringLinyi UniversityLinyi 276005China College of ChemistryChemical Engineering and Materials ScienceCooperative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of ShandongShandong Normal UniversityJinan 250014China 

出 版 物：《Science China Chemistry》 (中国科学（化学英文版）)

年 卷 期：2020年第63卷第4期

页      面：546-553页

核心收录：

学科分类：1007[医学-药学(可授医学、理学学位)] 1002[医学-临床医学] 07[理学] 070205[理学-凝聚态物理] 08[工学] 080501[工学-材料物理与化学] 0805[工学-材料科学与工程（可授工学、理学学位）] 100214[医学-肿瘤学] 10[医学] 0702[理学-物理学] 

基　　金：the National Natural Science Foundation of China(21876074,21605071,21775063) the Shandong Provincial Key Research and Development Program(2017CXZC1206,GG201809250462) the Shandong Provincial Natural Science Foundation Major Basic Research Project(ZR2018ZC0231) Taishan Scholars Program of Shandong Province(tsqn201812101) 

主　　题：RNA nanohydrogel phototherapy drug delivery gene therapy lung cancer 

摘      要：Conventional cancer combination therapy usually involves systemic delivery of anticancer drugs which may lead to the destruction of normal cells and physiological toxicity due to the lack of targeting ability and toxicity of drug carriers. In the present study, a triple combination nanosystem of gene therapy, chemotherapy and phototherapy delivered by multifunctional RNA nanohydrogels(RNA NHs) was established. By taking the advantages of DNA nanotechnology and rolling circle transcription(RCT), three lung cancer inhibitor microRNA(let-7 a, microRNA 34 a, microRNA 145) hairpins were integrated in one RNA NH nanoparticle, leading to the simultaneous silencing of three targeted m RNAs. Meanwhile, RNA NH carried doxorubicin(DOX, a chemotherapy drug) as well as 5,10,15,20-tetrakis(1-methylpyridinium-4-yl) porphyrin(TMPyP4, a photosensitizer) and delivered these drugs to cancer cells. It was demonstrated that lung cancer inhibitor microRNAs integrated in RNA NHs, DOX and TMPyP4 could play a synergistic anti-cancer role in multi-drug resistance cancer cells. Under the action of aptamer sequence S6 that was modified with cholesterol, the resulting RNA NHs were condensed to feasible size without the assistance of polyelectrolyte condensation reagents and showed cancer-specific cellular targeting. Subsequently, thousands of copies of miRNA together with chemotherapy drug as well as photosensitizer were delivered to cancer cells specifically, and an ideal synergistic treatment effect was achieved in vivo, thus playing a combined role of gene therapy, chemotherapy and phototherapy. Through this study, it can be concluded that the triple combination therapy nanosystem can overcome the multidrug resistance caused by the malfunction of genes in chemotherapy and shows a great potential in the field of multifunctional synergistic cancer treatment.