One Responsive Stone, Three Birds: Mn(III)‐Hemoporfin Frameworks with Glutathione‐Enhanced Degradation, MRI, and Sonodynamic Therapy,Advanced Healthcare Materials

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One Responsive Stone, Three Birds: Mn(III)‐Hemoporfin Frameworks with Glutathione‐Enhanced Degradation, MRI, and Sonodynamic Therapy
Advanced Healthcare Materials ( IF 10.0 ) Pub Date : 2020-12-04 , DOI: 10.1002/adhm.202001463
Peng Geng ₁ , Nuo Yu ₁ , Jiulong Zhang ₂ , Zilin Jin ₁ , Mei Wen ₁ , Qin Jiang ₁ , Li Kang ₃ , Chen Peng ₃ , Maoquan Li ₃ , Haijun Zhang _{3,

4} , Meifang Zhu ₁ , Zhigang Chen ₁

Affiliation

Ultrasound‐driven sonodynamic therapy (SDT) catches numerous attentions for destroying deep‐seated tumors, but its applications suffer from unsatisfactory therapeutic effects and metabolism. Furthermore, SDT is usually weakened by the complex tumor microenvironment, such as the overexpression of glutathione (GSH). To address these issues, Mn(III)‐hemoporfin frameworks (Mn(III)‐HFs) are reported as nanosonosensitizers by using biocompatible hematoporphyrin monomethyl‐ether (HMME) to coordinate with Mn(III) ions. Mn(III)‐HFs/PEG can react with GSH to produce Mn(II) ions and oxidized glutathione (GSSG), resulting in three fascinating features: 1) the redox reaction facilitates the decomposition of Mn(III)‐HFs/PEG and then collapse of nanostructures, improving the biodegradability; 2) Mn(II) ions with five unpaired 3d‐electrons exhibit better magnetic resonance imaging (MRI) ability compared to Mn(III) ions with four electrons; 3) both the depletion of endogenous GSH and the dissociated HMME boost ¹O₂ generation ability under US irradiation. As a result, when Mn(III)‐HFs/PEG dispersion is intravenously administered into mice, it exhibits high‐contrast T₁/T₂ dual‐modal MRI and significant suppression for the growth rate of the deep‐seated tumor. Furthermore, Mn(III)‐HFs/PEG can be efficiently metabolized from the mice. Therefore, Mn(III)‐HFs/PEG exhibit GSH‐enhanced degradation, MRI, and SDT effects, which provide some insights on the developments of other responsive nanosonosensitizers.

中文翻译：

一颗反应石，三只鸟：Mn(III)-Hemoporfin Frameworks with Glutathione-Enhanced Degradation, MRI, and Sonodynamic Therapy

超声驱动的声动力疗法（SDT）在破坏深部肿瘤方面引起了广泛关注，但其应用存在治疗效果和代谢不理想的问题。此外，复杂的肿瘤微环境通常会削弱 SDT，例如谷胱甘肽 (GSH) 的过表达。为了解决这些问题，据报道，Mn(III)-血卟啉框架 (Mn(III)-HFs) 通过使用生物相容性血卟啉单甲醚 (HMME) 与 Mn(III) 离子配位作为纳米声敏剂。Mn(III)-HFs/PEG 可与 GSH 反应生成 Mn(II) 离子和氧化型谷胱甘肽 (GSSG)，从而产生三个引人入胜的特征：1) 氧化还原反应促进 Mn(III)-HFs/PEG 的分解和然后破坏纳米结构，提高生物降解性；2) 与具有四个电子的 Mn(III) 离子相比，具有五个不成对 3d 电子的 Mn(II) 离子表现出更好的磁共振成像 (MRI) 能力；3) 内源性 GSH 的消耗和分离的 HMME 增强美国辐照下的¹或_{2代能力。}因此，当将 Mn(III)-HFs/PEG 分散体静脉注射到小鼠体内时，它表现出高对比度的T ₁ / T ₂双模态 MRI 和对深部肿瘤生长速度的显着抑制。此外，Mn(III)-HFs/PEG 可以从小鼠体内有效代谢。因此，Mn(III)-HFs/PEG 表现出 GSH 增强的降解、MRI 和 SDT 效应，这为其他响应性纳米声敏剂的发展提供了一些见解。

更新日期：2021-02-03

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