Trisulfide Bond-Mediated Molecular Phototheranostic Platform for “Activatable” NIR-II Imaging-Guided Enhanced Gas/Chemo-Hypothermal Photothermal Therapy,Advanced Science

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Trisulfide Bond-Mediated Molecular Phototheranostic Platform for “Activatable” NIR-II Imaging-Guided Enhanced Gas/Chemo-Hypothermal Photothermal Therapy
Advanced Science ( IF 14.3 ) Pub Date : 2023-11-20 , DOI: 10.1002/advs.202304104
Gui-Long Wu ₁ , Fen Liu ₁ , Na Li ₁ , Qian Fu ₁ , Cheng-Kun Wang ₁ , Sha Yang ₁ , Hao Xiao ₁ , Li Tang _{1,

2} , Feirong Wang ₁ , Wei Zhou ₁ , Wenjie Wang ₁ , Qiang Kang ₁ , Zelong Li ₁ , Nanyun Lin ₁ , Yinyin Wu ₁ , Guodong Chen ₃ , Xiaofeng Tan _{1,

4,

5} , Qinglai Yang _{1,

3,

4,

5}

Affiliation

Tumor microenvironment (TME)-triggered phototheranostic platform offers a feasible strategy to improve cancer diagnosis accuracy and minimize treatment side effects. Developing a stable and biocompatible molecular phototheranostic platform for TME-activated second near-infrared (NIR-II) fluorescence imaging-guided multimodal cascade therapy is a promising strategy for creating desirable anticancer agents. Herein, a new NIR-II fluorescence imaging-guided activatable molecular phototheranostic platform (IR-FEP-RGD-S-S-S-Fc) is presented for actively targeted tumor imaging and hydrogen sulfide (H₂S) gas-enhanced chemodynamic-hypothermal photothermal combined therapy (CDT/HPTT). It is revealed for the first time that the coupling distance between IR-FE and ferrocene is proportional to the photoinduced electron transfer (PET), and the aqueous environment is favorable for PET generation. The part of Cyclic-RGDfK (cRGDfk) peptides can target the tumor and benefit the endocytosis of nanoparticles. The high-concentration glutathione (GSH) in the TME will separate the fluorescence molecule and ferrocene by the GSH-sensitive trisulfide bond, realizing light-up NIR-II fluorescence imaging and a cascade of trimodal synergistic CDT/HPTT/gas therapy (GT). In addition, the accumulation of hydroxyl radicals (•OH) and down-regulation of glutathione peroxidase 4 (GPX4) can produce excessive harmful lipid hydroperoxides, ultimately leading to ferroptosis.

中文翻译：

用于“可激活”NIR-II 成像引导增强气体/化学低温光热治疗的三硫键介导的分子光治疗平台

肿瘤微环境（TME）触发的光治疗平台提供了一种可行的策略，以提高癌症诊断的准确性并最大限度地减少治疗副作用。为 TME 激活的第二近红外 (NIR-II) 荧光成像引导的多模式级联疗法开发稳定且生物相容的分子光治疗平台是创造理想抗癌药物的一个有前景的策略。在此，提出了一种新的 NIR-II 荧光成像引导可激活分子光治疗平台 (IR-FEP-RGD-SSS-Fc)，用于主动靶向肿瘤成像和硫化氢 (H ₂ S) 气体增强化学动力学-低温光热联合治疗（CDT/HPTT）。首次揭示IR-FE与二茂铁之间的耦合距离与光致电子转移（PET）成正比，并且水环境有利于PET的生成。环-RGDfK（cRGDfk）肽部分可以靶向肿瘤并有利于纳米颗粒的内吞作用。 TME中的高浓度谷胱甘肽（GSH）将通过GSH敏感的三硫键将荧光分子与二茂铁分离，实现点亮NIR-II荧光成像和级联三模协同CDT/HPTT/气体治疗（GT）。此外，羟自由基（·OH）的积累和谷胱甘肽过氧化物酶4（GPX4）的下调可产生过量的有害脂质氢过氧化物，最终导致铁死亡。

更新日期：2023-11-20

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