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

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*

*此作品的通讯作者

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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. [Figure not available: see fulltext.]

源语言英语
页(从-至)9160-9168
页数9
期刊Nano Research
15
10
DOI
出版状态已出版 - 10月 2022

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Yu, C., Li, K., Xu, L., Li, B., Li, C., Guo, S., Li, Z., Zhang, Y., Hussain, A., Tan, H., Zhang, M., Zhao, Y., Huang, Y., & Liang, X. J. (2022). siRNA-functionalized lanthanide nanoparticle enables efficient endosomal escape and cancer treatment. Nano Research, 15(10), 9160-9168. https://doi.org/10.1007/s12274-022-4573-2