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过氧化氢激活纳米颗粒用于癌症的发光成像和触发光动力疗法。

Hydrogen Peroxide-Activatable Nanoparticles for Luminescence Imaging and Triggerable Photodynamic Therapy of Cancer.

机构信息

Department of Pharmaceutics, College of Pharmacy, Third Military Medical University (Army Medical University), Chongqing 400038, China.

Department of Pharmacy, General Hospital of Southern Theatre Command, PLA, Guangzhou 510010, China.

出版信息

ACS Appl Mater Interfaces. 2020 Apr 15;12(15):17230-17243. doi: 10.1021/acsami.0c01413. Epub 2020 Mar 31.

Abstract

Abnormally increased reactive oxygen species (ROS) are intimately related to the development and metastasis of cancer. Since hydrogen peroxide (HO) is a major component of ROS, molecular imaging and selective treatment in response to high HO are intriguing for the management of cancers. Herein, we report novel self-assembly luminescent nanoparticles, which can be activated by HO, thereby serving as an effective nanotheranostics for luminescence imaging and photodynamic therapy (PDT) of tumors with high HO. This functional nanomedicine was assembled from an amphiphilic conjugate (defined as CLP) based on chlorin e6 (Ce6) simultaneously conjugated with luminol and poly(ethylene glycol), exhibiting a well-defined core-shell nanostructure. Upon triggering by pathologically relevant levels of HO, CLP nanoparticles produced luminescence due to the luminol unit and simultaneous excitation of Ce6 by chemiluminescence resonance energy transfer, enabling and imaging of tumors with highly expressed HO. In addition, excited Ce6 can produce singlet oxygen (O) for PDT of HO-high tumors and inhibiting lung metastasis, which was demonstrated by and experiments. Furthermore, preliminary studies revealed the biosafety of CLP nanoparticles. Consequently, the self-illuminating nanoparticles are promising for noninvasive imaging and therapy of tumors with high expression of HO.

摘要

异常增加的活性氧 (ROS) 与癌症的发展和转移密切相关。由于过氧化氢 (HO) 是 ROS 的主要成分,因此针对高 HO 的分子成像和选择性治疗对于癌症的管理具有吸引力。在这里,我们报告了一种新型的自组装发光纳米粒子,它可以被 HO 激活,从而作为具有高 HO 的肿瘤的发光成像和光动力治疗 (PDT) 的有效纳米治疗药物。这种功能纳米药物是由基于叶绿素 e6 (Ce6) 的两亲性缀合物 (定义为 CLP) 组装而成的,该缀合物同时与发光氨和聚乙二醇缀合,具有明确定义的核壳纳米结构。在受到病理相关水平的 HO 触发后,CLP 纳米粒子由于发光氨单元和化学发光共振能量转移同时激发 Ce6 而产生发光,从而能够对高表达 HO 的肿瘤进行成像和成像。此外,激发的 Ce6 可以产生单线态氧 (O) 用于 HO-高肿瘤的 PDT 和抑制肺转移,这通过 和 实验得到了证明。此外,初步研究表明 CLP 纳米粒子具有生物安全性。因此,自发光纳米粒子有望用于高表达 HO 的肿瘤的无创成像和治疗。

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