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上/下转换发光染料敏化的稀土纳米颗粒用于近红外二区荧光成像引导的脑胶质瘤按需气体治疗。

Dye-Sensitized Rare Earth Nanoparticles with Up/Down Conversion Luminescence for On-Demand Gas Therapy of Glioblastoma Guided by NIR-II Fluorescence Imaging.

机构信息

Center for Molecular Imaging and Nuclear Medicine, State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Radiation Protection, Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University, 199 Ren Ai Road, Suzhou Industrial Park, Suzhou, 215123, China.

出版信息

Adv Healthc Mater. 2022 Feb;11(3):e2102042. doi: 10.1002/adhm.202102042. Epub 2021 Nov 25.

DOI:10.1002/adhm.202102042
PMID:34787378
Abstract

As the primary malignant tumor in the brain, glioblastoma exhibits a high mortality due to the challenges for complete treatment by conventional therapeutic methods. It is of great importance to develop innovative therapeutic agents and methods for treatment of glioblastoma. In this work, the imaging and therapy of glioblastoma are reported by using dye sensitized core-shell NaYF :Yb/Tm@NaYF :Nd nanoparticles with strong up/down-conversion luminescence, of which the ultraviolet up-conversion emissions at 348 and 365 nm are significantly enhanced by nearly 28 times and used to control the release of SO from 5-Amino-1,3-dihydrobenzo[c]thiophene 2,2-dioxide prodrug for gas therapy, and the second near-infrared (NIR-II) down conversion emission at 1340 nm is increased five times and applied for imaging. It is revealed that the released SO molecules not only cause oxidative stress damage of tumor cells, but also induce their pro-death autophagy by down-regulating the expression of p62 and up-regulating the ratio of LC3-II/LC3-I, ultimately inhibiting tumor growth. The work demonstrates the great potential of rare earth nano-platform with functions of NIR-II imaging and photo-controlled gas therapy in the diagnosis and treatment of orthotopic glioblastoma.

摘要

作为大脑中的原发性恶性肿瘤,胶质母细胞瘤由于常规治疗方法难以完全治疗,死亡率很高。开发用于治疗胶质母细胞瘤的创新治疗剂和方法非常重要。在这项工作中,使用具有强上/下转换发光的染料敏化核壳 NaYF:Yb/Tm@NaYF:Nd 纳米粒子来报告胶质母细胞瘤的成像和治疗,其中紫外上转换发射在 348 和 365nm 处分别显著增强近 28 倍,用于控制 5-氨基-1,3-二氢苯并[c]噻吩 2,2-二氧化物前药中 SO 的释放,用于气体治疗,第二个近红外(NIR-II)下转换发射在 1340nm 处增加了五倍,用于成像。结果表明,释放的 SO 分子不仅会引起肿瘤细胞的氧化应激损伤,还会通过下调 p62 的表达和上调 LC3-II/LC3-I 的比值来诱导其促死亡自噬,从而最终抑制肿瘤生长。这项工作证明了具有 NIR-II 成像和光控气体治疗功能的稀土纳米平台在原位胶质母细胞瘤的诊断和治疗中的巨大潜力。

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