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.
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).
