Molecular Probe Crossing Blood–Brain Barrier for Bimodal Imaging–Guided Photothermal/Photodynamic Therapies of Intracranial Glioblastoma,Advanced Functional Materials

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Molecular Probe Crossing Blood–Brain Barrier for Bimodal Imaging–Guided Photothermal/Photodynamic Therapies of Intracranial Glioblastoma
Advanced Functional Materials ( IF 18.5 ) Pub Date : 2020-02-07 , DOI: 10.1002/adfm.201909117
Bo Li ₁ , Hong Xiao _{1,

2} , Mingyue Cai ₃ , Xiaoxia Li ₁ , Xiaolin Xu ₄ , Shiyin Wang ₁ , Si Huang ₂ , Yong Wang _{1,

2} , Du Cheng ₁ , Pengfei Pang ₅ , Hong Shan ₅ , Xintao Shuai ₅

Affiliation

Currently, treatment of intracranial diseases still remains a great challenge because the blood–brain barrier (BBB) blocks access of most drugs to the central nervous system. Herein, a theranostic small molecular probe, iRGD‐ICG‐Lys‐DTPA@Gd (iRGD‐ILD), capable of crossing BBB is developed. Owing to the small molecular size and α_vβ₃ integrin receptor–mediated transcytosis, this tailor‐made molecular probe integrating the fluorescence and magnetic resonance imaging functions effectively passes through BBB to target tumor cells even in the early stage of glioblastoma multiforme (GBM), thereby allowing a bimodal imaging–guided therapy of GBM. The reactive oxygen species and heat generated by the ICG moiety under the 808 nm laser irradiation exert photodynamic/photothermal therapeutic effects, which results in significantly inhibited tumor growth and prolonged median survival of C6‐Luc glioma‐bearing mice. Notably, the integration of FDA‐approved clinically available agents, e.g., ICG, DTPA and Gd, into a molecular probe may ensure desirable biocompatibility and biosafety for in vivo applications. Overall, the results highlight the potential of a water‐soluble small molecule as a novel theranostic probe for highly effective GBM treatment.

中文翻译：

分子探针穿越血脑屏障的双峰成像指导的颅内胶质母细胞瘤的光热/光动力疗法

目前，颅内疾病的治疗仍然是一个巨大的挑战，因为血脑屏障（BBB）阻止了大多数药物进入中枢神经系统。本文开发了一种能够穿越血脑屏障的治疗性小分子探针iRGD-ICG-Lys-DTPA @ Gd（iRGD-ILD）。由于小分子大小和α _v β ₃整合素受体介导的胞吞作用，这种量身定制的分子探针结合了荧光和磁共振成像功能，即使在多形性胶质母细胞瘤（GBM）的早期，也能有效地通过BBB靶向肿瘤细胞，从而实现了GBM的双峰成像指导治疗。ICG部分在808 nm激光照射下产生的活性氧和热量发挥了光动力/光热治疗作用，从而显着抑制了C6-Luc胶质瘤小鼠的肿瘤生长并延长了其中位生存期。值得注意的是，将FDA批准的临床可用药物（例如ICG，DTPA和Gd）整合到分子探针中，可以确保体内应用具有理想的生物相容性和生物安全性。总体，

更新日期：2020-03-19

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