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可转化液态金属纳米药物

Transformable liquid-metal nanomedicine.

作者信息

Lu Yue, Hu Quanyin, Lin Yiliang, Pacardo Dennis B, Wang Chao, Sun Wujin, Ligler Frances S, Dickey Michael D, Gu Zhen

机构信息

Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Raleigh, North Carolina 27695, USA.

Division of Molecular Pharmaceutics and Center for Nanotechnology in Drug Delivery, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.

出版信息

Nat Commun. 2015 Dec 2;6:10066. doi: 10.1038/ncomms10066.

Abstract

To date, numerous inorganic nanocarriers have been explored for drug delivery systems (DDSs). However, the clinical application of inorganic formulations has often been hindered by their toxicity and failure to biodegrade. We describe here a transformable liquid-metal nanomedicine, based on a core-shell nanosphere composed of a liquid-phase eutectic gallium-indium core and a thiolated polymeric shell. This formulation can be simply produced through a sonication-mediated method with bioconjugation flexibility. The resulting nanoparticles loaded with doxorubicin (Dox) have an average diameter of 107 nm and demonstrate the capability to fuse and subsequently degrade under a mildly acidic condition, which facilitates release of Dox in acidic endosomes after cellular internalization. Equipped with hyaluronic acid, a tumour-targeting ligand, this formulation displays enhanced chemotherapeutic inhibition towards the xenograft tumour-bearing mice. This liquid metal-based DDS with fusible and degradable behaviour under physiological conditions provides a new strategy for engineering theranostic agents with low toxicity.

摘要

迄今为止,人们已探索了众多无机纳米载体用于药物递送系统(DDSs)。然而,无机制剂的临床应用常常因其毒性和无法生物降解而受阻。我们在此描述一种可转化的液态金属纳米药物,其基于由液相共晶镓铟核和硫醇化聚合物壳组成的核壳纳米球。这种制剂可通过具有生物共轭灵活性的超声介导方法简单制备。所得负载阿霉素(Dox)的纳米颗粒平均直径为107纳米,并显示出在轻度酸性条件下融合并随后降解的能力,这有助于细胞内化后阿霉素在酸性内涵体中释放。配备有肿瘤靶向配体透明质酸,这种制剂对荷异种移植瘤小鼠表现出增强的化疗抑制作用。这种在生理条件下具有可融合和可降解行为的基于液态金属的DDS为设计低毒诊疗剂提供了一种新策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6e8/4686762/d9032134d46a/ncomms10066-f1.jpg

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