Lipid-conjugated siRNA hitchhikes endogenous albumin for tumor immunotherapy  

作　　者：Bo Hu Sudong Kong Yuhua Weng Deyao Zhao Abid Hussain Qingze Jiao Shijing Zhan Ling Qiu Jianguo Lin Minhao Xie Bo Li Yuanyu Huang 

机构地区：[1]School of Life Science,Advanced Research Institute of Multidisciplinary Science,School of Medical Technology,Key Laboratory of Molecular Medicine and Biotherapy,Key Laboratory of Medical Molecule Science and Pharmaceutics Engineering,Beijing Key Laboratory for Separation and Analysis in Biomedicine and Pharmaceuticals,Beijing Institute of Technology,Beijing 100081,China [2]School of Chemical and Material Engineering,Jiangnan University,Wuxi 214122,China [3]NHC Key Laboratory of Nuclear Medicine,Jiangsu Key Laboratory of Molecular Nuclear Medicine,Jiangsu Institute of Nuclear Medicine,Wuxi 214063,China [4]Department of Radiation Oncology,The First Affiliated Hospital of Zhengzhou University,Zhengzhou 450000,China [5]School of Materials and the Environment,Beijing Institute of Technology,Zhuhai 519085,China [6]Rigerna Therapeutics,Suzhou 215127,China

出　　处：《Chinese Chemical Letters》2023年第11期202-208,共7页中国化学快报（英文版）

基　　金：supported by the Beijing Natural Science Foundation(No.7214302);the Natural Science Foundation of Guangdong Province(No.2019A1515010776);the National Natural Science Foundation of China(Nos.31901053,32001008,32171394);the Beijing-Tianjin-Hebei Basic Research Cooperation Project(No.19JCZDJC64100);the Beijing Nova Program from Beijing Municipal Science&Technology Commission(No.Z201100006820005);the National Key Research&Development Program of China(Nos.2021YFE0106900,2021YFA1201000,2021YFC2302400).

摘　　要：With the development of a small interfering RNA(siRNA)delivery strategy,increasing siRNA therapeutics for tumor treatment appeared in clinical trials and pre-clinical development.However,the test results of such therapeutics unveiled that efficient siRNA delivery to tumor tissues is still challenging.Albumin is considered an ideal carrier for delivering hydrophobic agents into tumor tissue because it is highly concentrated and long-circulating in blood and has propensity of tumor enrichment.Herein,we synthesized lipid conjugated siRNAs(LsiRNAs),which showed high affinity to albumin.Mechanistically,LsiRNAs non-covalently bind to the hydrophobic core of albumin through its octadecyl tails.The small size of albumin/LsiRNAs allows the complex to penetrate tumor tissue efficiently.Biodistribution test proved that albumin extremely prolonged circulation time and increased tumor retention of associated LsiRNAs.Notably,LsiRNA against programmed death ligand-1(Pdl1)efficiently suppressed tumor growth as well as prolonged survival time of tumor bearing mice by increasing infiltration of CD8^(+)T cells as well as promoted the maturation of dendritic cells both in tumor and lymph.Together,LsiRNAs provide a simple but effective way for siRNA tumor delivery that“hitchhikes”on albumin.

关 键 词：ALBUMIN SIRNA Lipid conjugate Tumor treatment Immunotherapy 

分 类 号：R73[医药卫生—肿瘤]