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超分子化学介导的金纳米颗粒与阿霉素的相互作用

Interaction of gold nanoparticles with Doxorubicin mediated by supramolecular chemistry.

作者信息

Marcelo Gema, Kaplan Ekrem, Tarazona M Pilar, Mendicuti Francisco

机构信息

Departamento de Química Analítica, Química Física e Ingeniería Química, Universidad de Alcalá, Alcalá de Henares 28871, Madrid, Spain.

Departamento de Química Analítica, Química Física e Ingeniería Química, Universidad de Alcalá, Alcalá de Henares 28871, Madrid, Spain.

出版信息

Colloids Surf B Biointerfaces. 2015 Apr 1;128:237-244. doi: 10.1016/j.colsurfb.2015.01.041. Epub 2015 Feb 4.

Abstract

A copolymer containing β-cyclodextrin, catechol and polyethylene glycol groups in its side chain was designed for the in situ synthesis and coating of gold nanoparticles (Au@PEG-CD NPs). These platforms were designed as a smart carrier and traceable delivery probe of the chemotherapeutic Doxorubicin drug (Dox). The coated polymer forms stable complexes with Dox in water with a high binding constant (K=2.3×10(4) M(-1) at 25°C), which is one hundred times greater than those reported for its complexation with native βCD. Therefore, Au@PEG-CD NPs were able to load 0.01 mg of the drug per mg of NP and to release up to 60% of it in 48 h at 37°C. In addition, Au@PEG-CD NPs had the capacity to act as a quencher of Dox fluorescence when it was complexed with βCD in the NP organic shell. This feature allows the Dox release to be tracked by monitoring the recovery of its fluorescence in real time. Therefore, the Dox release kinetics and the influence of temperature on the thermal stability of Dox/CD complexes on Au@PEG-CD NP were investigated. The increase in temperature favors the dissociation of the complexes and subsequent Dox release from the NP. The first order rate constant for drug releasing was 1.1×10(-2) min(-1) with a half-life time of 63 min at 37°C. Finally, the great potential of the carrier/probe double nature of Au@PEG-CD NPs was demonstrated in real time inside HeLa cells.

摘要

设计了一种在其侧链中含有β-环糊精、儿茶酚和聚乙二醇基团的共聚物,用于金纳米颗粒(Au@PEG-CD NPs)的原位合成和包覆。这些平台被设计为化疗药物阿霉素(Dox)的智能载体和可追踪递送探针。包覆的聚合物在水中与Dox形成稳定的复合物,其结合常数较高(25°C时K = 2.3×10⁴ M⁻¹),这比其与天然β-环糊精络合所报道的结合常数大一百倍。因此,Au@PEG-CD NPs能够每毫克纳米颗粒负载高达0.01毫克的药物,并在37°C下48小时内释放高达60%的药物。此外,当Dox在纳米颗粒有机壳层中与β-环糊精络合时,Au@PEG-CD NPs能够作为Dox荧光的猝灭剂。这一特性使得可以通过实时监测其荧光恢复来追踪Dox的释放。因此,研究了Dox在Au@PEG-CD NP上的释放动力学以及温度对Dox/环糊精复合物热稳定性的影响。温度升高有利于复合物的解离以及随后Dox从纳米颗粒中的释放。在37°C下,药物释放的一级速率常数为1.1×10⁻² min⁻¹,半衰期为63分钟。最后,在HeLa细胞内实时证明了Au@PEG-CD NPs载体/探针双重性质的巨大潜力。

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