过渡金属（钼）掺杂的药物样构象纳米结构，用于增强的癌症治疗与诊断（Mn2+/Mn4+ 和 Mo5+/Mo6+价态变换）

Transition Metal (Molybdenum)-Doped Drug-like Conformational Nanoarchitectonics with Altered Valence States (Mn2+/Mn4+ and Mo5+/Mo6+) for Augmented Cancer Theranostics

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MOLECULAR PHARMACEUTICS

影响因子:4.5

分区:医学2区 / 药学2区医学：研究与实验3区

发表日期:2024 Nov 04

作者: Hong-Ying Xia, Ying Zhao, Ruo-Yin Meng, Ai-Zheng Chen, Shi-Bin Wang, Ranjith Kumar Kankala

DOI: 10.1021/acs.molpharmaceut.4c00896

keywords: chemodynamic therapy; conformational nanoarchitectures; doping metals; glutathione oxidation; manganese dioxide; molybdenum

摘要

尽管癌症治疗取得了进展，但利用纳米颗粒递送活性药物成分（API）仍面临挑战，主要包括药物载荷传递失败、靶向能力差和生物分布不佳，阻碍其临床转化。近年来，设计具有内在治疗功能的材料引起了极大关注，促进了各种智能治疗纳米平台的发展。在本研究中，我们展示了钼（Mo）掺杂二氧化锰（MnO2）纳米结构的制备，这些结构具有诊断（磁共振成像，MRI）和治疗（化学动力治疗，CDT）功能。简便的水热法制备的Mo掺杂MnO2花状纳米结构具有可调节的形貌和尺寸，提供精准的治疗效果，具有优异的生物相容性和在肿瘤微环境中的生物降解性。掺杂Mo物质引起的缺陷表现出过氧化物酶和氧化酶活性，增强谷胱甘肽（GSH）的氧化。具有两对不同价态（Mn2+/Mn4+ 和 Mo5+/Mo6+）的金属离子对及其相互作用，显著增强了Fenton样反应，产生有毒的羟基自由基（•OH），实现了化学动力治疗辅助的抗肿瘤效果。作为固有的T1-MRI剂，这些MnO2纳米粒子在体外展现出优异的MRI效率。我们相信，这些具有两对变价态的构象Mo掺杂MnO2纳米结构，可以在药物无关的治疗中发挥潜力。

Abstract

Despite the advancements in cancer therapy, delivering active pharmaceutical ingredients (APIs) using nanoparticles remains challenging due to the failed conveyance of the required drug payload, poor targeting ability, and poor biodistribution, hampering their clinical translation. Recently, the appropriate design of materials with intrinsic therapeutic functionalities has garnered enormous interest in the development of various intelligent therapeutic nanoplatforms. In this study, we demonstrate the fabrication of transition metal (molybdenum, Mo)-doped manganese dioxide (MnO2) nanoarchitectures, exhibiting diagnostic (magnetic resonance imaging, MRI) and therapeutic (chemodynamic therapy, CDT) functionalities. The facile hydrothermal approach-assisted Mo-doped MnO2 flower-like nanostructures offered tailorable morphologies in altered dimensions, precise therapeutic effects, exceptional biocompatibility, and biodegradability in the tumor microenvironment. The resultant defects due to doped Mo species exhibited peroxidase and oxidase activities, improving glutathione (GSH) oxidation. The two sets of variable valence metal ion pairs (Mn2+/Mn4+ and Mo5+/Mo6+) and their interplay could substantially improve the Fenton-like reaction and generate toxic hydroxyl radicals (•OH), thus achieving CDT-assisted antitumor effects. As inherent T1-MRI agents, these MnO2 nanoparticles displayed excellent MRI efficacy in vitro. Together, we believe that these conformational Mo-doped MnO2 nanoarchitectures with two pairs of variable valence states could potentiate drugless therapy in pharmaceutics.