In vitro evaluation of biodegradable lignin-based nanoparticles for drug delivery and enhanced antiproliferation effect in cancer cells

In vitro evaluation of biodegradable lignin-based nanoparticles for drug delivery and enhanced antiproliferation effect in cancer cells
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DOI:
10.1016/j.biomaterials.2016.12.034
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发表时间:
2017-03-01
期刊:
影响因子:
14
通讯作者:
Santos, Helder A.
Santos, Helder A.
中科院分区:
工程技术1区
文献类型:
--
作者:
Figueiredo, Patricia;Lintinen, Kalle;Santos, Helder A.

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目前,纳米系统已被开发和应用为不同的生物医学应用的有前途的车辆。我们已经开发了三种木质素纳米颗粒(LNP):纯木质素纳米颗粒(pLNP),铁(III)络合的木质素纳米颗粒(Fe-LNP),和Fe 3 O 4注入的木质素纳米颗粒(Fe 3 O 4-LNP)具有圆形形状,窄的尺寸分布,降低的多分散性和良好的稳定性,在pH 7.4。LNP在所有测试的细胞系中显示出低细胞毒性,并且在孵育12小时后溶血率低于12%。此外,它们以小程度和时间依赖性方式诱导过氧化氢产生,并且与细胞的相互作用随时间增加,表现出剂量依赖性细胞摄取。关于药物负载,pLNP显示出有效负载水溶性差的药物和其他细胞毒性剂(例如索拉非尼和苯并甘菊环(BZL))的能力,并以持续的方式改善它们在pH 5.5和7.4下的释放曲线。此外,BZL-pLNPs提出了一个增强的抗增殖作用,在不同的细胞相比,纯BZL,并显示了最大的抑制浓度范围从0.64至12.4 μ M孵育24小时后。总的来说,LNPs是药物递送应用的有希望的候选者,并且Fe 3 O 4-LNPs的超顺磁性行为使它们有希望用于癌症治疗和诊断,例如磁靶向和磁共振成像。(C)2017爱思唯尔有限公司版权所有
Currently, nanosystems have been developed and applied as promising vehicles for different biomedical applications. We have developed three lignin nanoparticles (LNPs): pure lignin nanoparticles (pLNPs), iron(III)-complexed lignin nanoparticles (Fe-LNPs), and Fe3O4-infused lignin nanoparticles (Fe3O4-LNPs) with round shape, narrow size distribution, reduced polydispersity and good stability at pH 7.4. The LNPs showed low cytotoxicity in all the tested cell lines and hemolytic rates below 12% after 12 h of incubation. Additionally, they induced hydrogen peroxide production in a small extent and time-dependent manner, and the interaction with the cells increased over time, exhibiting a dose-dependent cell uptake. Concerning the drug loading, pLNPs showed the capacity to efficiently load poorly water-soluble drugs and other cytotoxic agents, e.g. sorafenib and benzazulene (BZL), and improve their release profiles at pH 5.5 and 7.4 in a sustained manner. Furthermore, the BZL-pLNPs presented an enhanced antiproliferation effect in different cells compared to the pure BZL and showed a maximal inhibitory concentration ranging from 0.64 to 12.4 mu M after 24 h incubation. Overall, LNPs are promising candidates for drug delivery applications, and the superparamagnetic behavior of Fe3O4-LNPs makes them promising for cancer therapy and diagnosis, such as magnetic targeting and magnetic resonance imaging. (C) 2017 Elsevier Ltd. All rights reserved.