siRNA-functionalized lanthanide nanoparticle enables efficient endosomal escape and cancer treatment  

作　　者：Chanchan Yu Kun Li Lin Xu Bo Li Chunhui Li Shuai Guo Ziyue Li Yuquan Zhang Abid Hussain Hong Tan Mengyu Zhang Yongxiang Zhao Yuanyu Huang Xing-Jie Liang 

机构地区：[1]School of Life Science,Advanced Research Institute of Multidisciplinary Science,School of Medical Technology(Institute of Engineering Medicine),Key Laboratory of Molecular Medicine and Biotherapy,Key Laboratory of Medical Molecule Science and Pharmaceutics Engineering,Beijing Institute of Technology,Beijing 100081,China [2]CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety,CAS Center for Excellence in Nanoscience,National Center for Nanoscience and Technology of China,Beijing 100190,China [3]National Center for International Research of Biological Targeting Diagnosis and Therapy,Guangxi Key Laboratory of Biological Targeting Diagnosis and Therapy Research,Guangxi Medical University,Nanning 530021,China

出　　处：《Nano Research》2022年第10期9160-9168,共9页纳米研究（英文版）

基　　金：supported by the Beijing Nova Program from Beijing Municipal Science&Technology Commission(No.Z201100006820005);the Beijing-Tianjin-Hebei Basic Research Cooperation Project(No.19JCZDJC64100);the National Key Research&Development Program of China(Nos.2018YFE0117800,2021YFA1201000,and 2021YFE0106900);the National Natural Science Foundation of China(Nos.32030060 and 31871003);the Natural Science Foundation of China international collaboration key project(No.51861135103).

摘　　要：Attaching DNA/RNA to nanomaterials is the basis for nucleic acid-based assembly and drug delivery.Herein,we report that small interfering RNA(siRNA)effectively coordinates with ligand-free lanthanide nanoparticles(NaGdF4 NPs),and forms siRNA/NaGdF4 spherical nucleic acids(SNA).The coordination is primarily attributed to the interaction between Gd and phosphate backbone of the siRNA.Surprisingly,an efficient encapsulation and rapid endosomal escape of siRNA from the endosome/lysosome were achieved,due to its flexible ability to bound to phospholipid head of endosomal membrane,thereby disrupting the membrane structure.Resorting to the dual properties of NaGdF4 NPs,siRNA loading,and endosomal escape,siRNA targeting programmed cell death-ligand 1(siPD-L1)/NaGdF4 SNA triggers significant gene silencing in vitro and in vivo,and effectively represses the tumor growth in both CT26 tumor model and 4T1 orthotopic murine model.

关 键 词：coordination chemistry nuclei acid lanthanide nanomaterials small interfering RNA(siRNA)delivery endosome escape 

分 类 号：TB383[一般工业技术—材料科学与工程] R730.5[医药卫生—肿瘤]