Model-Based Nanoengineered Pharmacokinetics of Iron-Doped Copper Oxide for Nanomedical Applications.,Angewandte Chemie International Edition

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Model-Based Nanoengineered Pharmacokinetics of Iron-Doped Copper Oxide for Nanomedical Applications.
Angewandte Chemie International Edition ( IF 16.1 ) Pub Date : 2020-01-09 , DOI: 10.1002/anie.201912312
Hendrik Naatz _{1,

2} , Bella B Manshian _{3,

4} , Carla Rios Luci _{3,

4} , Vasiliki Tsikourkitoudi ₅ , Yiannis Deligiannakis ₅ , Johannes Birkenstock ₆ , Suman Pokhrel _{1,

2} , Lutz Mädler _{1,

2} , Stefaan J Soenen _{3,

4}

Affiliation

The progress in nanomedicine (NM) using nanoparticles (NPs) is mainly based on drug carriers for the delivery of classical chemotherapeutics. As low NM delivery rates limit therapeutic efficacy, an entirely different approach was investigated. A homologous series of engineered CuO NPs was designed for dual purposes (carrier and drug) with a direct chemical composition-biological functionality relationship. Model-based dissolution kinetics of CuO NPs in the cellular interior at post-exposure conditions were controlled through Fe-doping for intra/extra cellular Cu2+ and biological outcome. Through controlled ion release and reactions taking place in the cellular interior, tumors could be treated selectively, in vitro and in vivo. Locally administered NPs enabled tumor cells apoptosis and stimulated systemic anti-cancer immune responses. We clearly show therapeutic effects without tumor cells relapse post-treatment with 6 % Fe-doped CuO NPs combined with myeloid-derived suppressor cell silencing.

中文翻译：

用于纳米医学应用的基于模型的铁掺杂氧化铜纳米工程药代动力学。

使用纳米粒子（NP）的纳米医学（NM）的进展主要基于用于输送经典化疗药物的药物载体。由于 NM 递送率低限制了治疗效果，因此研究了一种完全不同的方法。一系列同源工程 CuO 纳米颗粒被设计用于双重目的（载体和药物），具有直接的化学成分-生物功能关系。在暴露后条件下，基于模型的 CuO NP 在细胞内部的溶解动力学通过 Fe 掺杂来控制细胞内/外 Cu2+ 和生物学结果。通过控制离子释放和细胞内部发生的反应，可以在体外和体内选择性地治疗肿瘤。局部施用的纳米颗粒使肿瘤细胞凋亡并刺激全身抗癌免疫反应。我们清楚地显示了用 6% Fe 掺杂的 CuO NP 联合骨髓源性抑制细胞沉默治疗后肿瘤细胞没有复发的治疗效果。

更新日期：2020-01-10

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