A Chlorotoxin-Directed Diselenide-Bridged Tumor-Homing Persistent Luminescence Nanoprobes Mediating Inhibition of Oxidative Phosphorylation for Long-Term Near-Infrared Imaging and Therapy of Glioblastoma,Advanced Functional Materials

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A Chlorotoxin-Directed Diselenide-Bridged Tumor-Homing Persistent Luminescence Nanoprobes Mediating Inhibition of Oxidative Phosphorylation for Long-Term Near-Infrared Imaging and Therapy of Glioblastoma
Advanced Functional Materials ( IF 18.5 ) Pub Date : 2022-09-19 , DOI: 10.1002/adfm.202209579
Jianglong Kong ₁ , Yuting Sun ₁ , Xiaohan Ge ₁ , Meiru Mao ₁ , Hongrui Yu ₁ , Yi Wang _{1,

2}

Affiliation

Glioblastoma (GBM) is the most prevailing malignant primary brain tumor, and the precise diagnosis of GBM has always been a challenge. Gboxin is a recently developed drug efficiently inhibiting the oxidative phosphorylation in GBM cells, and both the chlorotoxin (CLTX) and GBM cell membrane coating are capable of GBM targeting and tumor homing. Herein, the near-infrared (NIR) persistent luminescence (PL) nanoparticle, CUDZG, with a dual function of imaging and therapy is developed based on ZnGa₂O₄:Cr³⁺,Sn⁴⁺. CUDZG exhibits superior rechargeable NIR PL for at least 48 h with excellent tissue penetration in vivo, which enables the longstanding autofluorescence-free imaging of the orthotopic GBM. The tumor growth of both the orthotropic and subcutaneous GBM-bearing mice are significantly suppressed by CUDZG. This is the first-time report of 1) the integration of CLTX and cell membrane coating for drug delivery, 2) diselenide-based trigger release for anti-GBM therapy, and 3) the systemic delivery of Gboxin. This study also offers an example of the highly promising blood-brain penetrable drug carriers for precise diagnosis and therapy of central nervous system diseases.

中文翻译：

氯毒素导向的二硒化物桥接肿瘤归巢持久发光纳米探针介导氧化磷酸化抑制，用于胶质母细胞瘤的长期近红外成像和治疗

胶质母细胞瘤（GBM）是最常见的恶性原发性脑肿瘤，GBM的精确诊断一直是一个挑战。Gboxin 是最近开发的一种有效抑制 GBM 细胞氧化磷酸化的药物，氯毒素 (CLTX) 和 GBM 细胞膜涂层都能够靶向 GBM 和肿瘤归巢。在此，基于ZnGa ₂ O ₄ :Cr ³⁺ ,Sn ^{4+开发了具有成像和治疗双重功能的近红外（NIR）持久发光（PL）纳米粒子CUDZG}. CUDZG 表现出卓越的可充电 NIR PL 至少 48 小时，具有出色的体内组织穿透性，这使得原位 GBM 的长期无自发荧光成像成为可能。CUDZG 显着抑制正交各向异性和皮下 GBM 小鼠的肿瘤生长。这是 1) CLTX 和细胞膜涂层的整合用于药物递送，2) 用于抗 GBM 治疗的基于二硒化物的触发释放，以及 3) Gboxin 的全身递送的首次报告。该研究还为中枢神经系统疾病的精准诊断和治疗提供了极具前景的血脑穿透药物载体实例。

更新日期：2022-09-19

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