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BIT’s research group has made progress in the anti-tumor research of siRNA functionalized lanthanide nano materials

News Resource: Advanced Research Institute of Multidisciplinary Science

Editor: News Agency of BIT

Translator: Wang Yuxuan, News Agency of BIT

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Recently, Professor Huang Yuanyu's research group from Beijing Institute of Technology (BIT) has made important progress in the anti-tumor research of siRNA-functionalized lanthanide nano materials. Related research results has been published in Nano Research (First district of Chinese Academy of Sciences, IF = 10.269) titled “siRNA-functionalized lanthanide nanoparticle enables efficient endosomal escape and cancer treatment”. Postdoctoral Yu Chanchan and postgraduate Li Kun from the School of Materials Science and Advanced Research Institute of Multidisciplinary and School of Life Science are first authors. Researcher Liang Xingjie from The National Center for Nanoscience and Technology, Professor Huang Yuanyu from BIT and Professor Zhao Yongxiang of Guangxi Medical University are corresponding authors.

Lanthanide nanomaterials have unique optical, electrical, and magnetic properties. To date, much research has focused on the basic interaction between lanthanide ions and nucleotides/DNA in order to design nucleotides/nucleic acid-based functional nanomaterials with unique properties. The in-depth study of the interaction mechanism between double-stranded siRNA and lanthanide nanomaterials will help develop a new small interfering nucleic acid (siRNA) delivery system and be used in disease treatment. In this paper, the team studied the interaction mechanism between siRNA and ligand-free NaGdF4 nanoparticles (NPs). In neutral environment, the siRNA phosphate backbone coordinates with Gd on the surface of NaGdF4 NPs, forming siRNA/NaGdF4 spherical nucleic acids (SNA) NPs, and siRNA binds to the surface of nanomaterials. After entering the cell, under the endolysosomal acidic conditions, phosphate groups protonated, which reduces the affinity of siRNA for NaGdF4 NPs and results in the dissociation of siRNA from NaGdF4 NPs (Fig.1). The intracellular escape process of siRNA was observed by Confocal laser scanning microscope (CLSM), and researched the antitumor effect of siRNA/NaGdF4 system in two types of tumor-bearing mouse models at the same time.

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Fig.1 Schematic illustration of the interaction of NaGdF4 NPs with siRNA, and the escape process of siRNA-functionalized NaGdF4 NPs from the endosome.

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Fig.2 The interaction between siRNA and NaGdF4 NPs. (a) TEM image of the NaGdF4 NPs. (b) Element mapping of siRNA/NaGdF4 SNA. (c) DLS-recorded sizes of ligand-free NaGdF4 and siRNA/NaGdF4 SNA. (d) Schematic of the interaction mechanism. (e) Gel electrophoresis analysis under indicated siRNA/NaGdF4 NPs number ratios.

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Fig.3 Endosomal escape process of siRNA/NaGdF4 SNA. (a) CLSM images of subcellular localization of siRNA/NaGdF4 SNA in the CT26 cells at different transfection time. Scale bars, 25 μm. (b) and (c) The mean fluorescence intensity and Pearson’s correlation coefficient in assay of (a), respectively. (d) CLSM images under the influence of chloroquine and bafilomycin A1 after 4 h transfection. Scale bars, 25 μm. (e) The Pearson’s correlation coefficient recorded in assay of (d). (f) Relative PD-L1 mRNA expression when using inhibitors of chloroquine or bafilomycin A1. **** p < 0.0001.

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Fig.4 In vivo antitumor efficacy of siPD-L1/NaGdF4 SNA in 4T1 orthotopic model. (a) The experimental process and grouping information(b-d) The representative optical images of isolated tumors(b)  the tumor weights(c), and the tumor growth kinetics(d) of the mice receiving the treatment of PBS (G1), siNC/NaGdF4 SNA (G2), and siPD-L1/NaGdF4 SNA (G3). n = 7. (e) Relative PD-L1 mRNA expression in tumor tissues evaluated by RT-qPCR. (f) The lung photographs and H&E staining of lung tissues collected at day 22. Yellow circle, tumor nodules; scale bar, 100 μm. (g) Serum biochemistry parameters of mice at the end of the experiment.


Paper link: https://link.springer.com/article/10.1007/s12274-022-4573-2


Author profile attached:

Huang Yuanyu, professor and doctoral supervisor of BIT, is selected to be one of the national young talents and Beijing NOVA. He mainly focuses on nucleic acid technology and medicine / vaccines. Besides, he has published about 60 papers on Sci Adv, Signal Transduct Target Ther, etc. as a corresponding / first author, of which more than 30 papers with IF>10 and more than 90 papers in total, written more than 10 monographs and chapters, and applied for 16 patents. He has won the first prize of Guangxi science and Technology Award for Natural Science (the fifth completed), the "Future star" award of the Chinese American Society of Nanomedicine and Nano biotechnology, and other honors. What’s more, he is the secretary-general of Nanobiology Academic Subgroup of Biophysical Society of China, and the director or member of several other societies, the deputy editor of Exploration (published by Wiley), the (youth) editorial board of Chinese Chemical Letters, Progress in Biochemistry and Biophysics and other journals.

Team homepage: https://www.x-mol.com/groups/Yuanyu_Huang-BIT