文献类型：期刊文献

英文题名：Targeted OUM1/PTPRZ1 silencing and synergetic CDT/enhanced chemical therapy toward uveal melanoma based on a dual-modal imaging-guided manganese metal-organic framework nanoparticles

作者：Li, Yue[1,2];Li, Fang[1,2];Pan, Hui[1,2];Huang, Xiaolin[1,2];Yu, Jie[1,2];Liu, Xueru[1,2];Zhang, Qinghao[4];Xiao, Caiwen[1,2];Zhang, He[3];Zhang, Leilei[1,2]

机构：[1]Shanghai Jiao Tong Univ, Sch Med, Shanghai Peoples Hosp 9, Dept Ophthalmol, Shanghai 200011, Peoples R China;[2]Shanghai Key Lab Orbital Dis & Ocular Oncol, Shanghai 200011, Peoples R China;[3]Tongji Univ, Sch Life Sci & Technol, Shanghai 200292, Peoples R China;[4]East China Univ Sci & Technol, Shanghai 200237, Peoples R China

年份：2022

卷号：20

期号：1

外文期刊名：JOURNAL OF NANOBIOTECHNOLOGY

收录：;EI(收录号：20224513074239);WOS:【SCI-EXPANDED(收录号:WOS:000879578000002)】；

基金：This work was supported by grants from the National Natural Science Foundation of China (81972524 and 81602366) and the Science and Technology Commission of Shanghai (17DZ2260100), fund of the Ninth People's Hospital Affiliated to Medical College of Shanghai Jiaotong University (SYZ2015-010), and fund by Shanghai "Rising Stars of Medical Talent" Youth Development Program, Youth Medical Talents-Specialist Program.

语种：英文

外文关键词：Uveal melanoma; LncRNA OUM1; Protein tyrosine phosphorylation; ICG-siOUM1+siPTPRZ1+Cis@ MOF-PR; Fenton-like reaction; Magnetic resonance

摘要：Metastasis and chemical resistance are the most serious problems in the treatment of highly aggressive uveal melanoma (UM). The newly identified lncRNA OUM1 is overexpressed in UM, functions as a catalyst and regulates protein tyrosine phosphatase (PTP) activity by binding to PTP receptor type Z1 (PTPRZ1), which plays an important role in cell proliferation, metastasis and chemotherapy resistance in the UM microenvironment. Hence, siRNAs that selectively knocking down the lncRNA OUM1 (siOUM1) and its target gene PTPRZ1 (siPTPRZ1) were designed to inhibit the OUM1/PTPRZ1 pathway to reduce PTP activity, and this reduction in activity interrupts protein tyrosine phosphorylation, suppresses UM proliferation and metastasis and improves cisplatin sensitivity in UM cells. Then, to overcome the limitations of the difficulty of drug administration and traditional therapeutics, the indocyanine green (ICG)-labeled manganese metal-organic framework (MOF) nanoparticles (NPs) were fabricated and linked with arginine-glycineaspartate (RGD) peptide to carry siOUM1/siPTPRZ1 and cisplatin to achieve targeted siRNA interference-mediated therapy, enhanced cisplatin therapy and chemodynamic therapy. This NP system also has a dual-modal imaging ability because ICG is a near-infrared region fluorescent dye and manganese has the potential to be used in magnetic resonance imaging. This study verifies the significance of the newly discovered lncRNA OUM1 as a new therapeutic target for aggressive UM and provides a drug delivery NP system for precise treatment of UM accompanied with a dual-modal imaging ability.