Surface coating mediates the toxicity of polymeric nanoparticles towards human-like macrophages
Surface coating mediates the toxicity of polymeric nanoparticles towards human-like macrophages
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DOI：
10.1016/j.ijpharm.2014.11.042
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发表时间：
2015-03-30
影响因子：
5.8
通讯作者：
Fattal, Elias
中科院分区：
文献类型：
--
作者：
Grabowski, Nadege;Hillaireau, Herve;Fattal, Elias
本研究的目的是研究一系列聚（乳酸-羟基乙酸）（PLGA）纳米粒对类人THP-1巨噬细胞的毒性。以壳聚糖（CS）、泊洛沙姆188（PF 68）和聚乙烯醇（PVA）为稳定剂制备了带正电、带负电和中性的纳米粒（200 nm）。当在治疗相关浓度（体外高达0.1mg/mL）下使用时，所有测试的纳米颗粒都没有或几乎没有毒性迹象，如通过细胞线粒体活性、诱导凋亡和坏死、产生细胞内活性氧（ROS）和分泌促炎细胞因子所评估的。在高浓度（高于1 mg/mL）下，发现稳定剂的存在可诱导细胞毒性，无论稳定剂本身的毒理学模式如何。虽然无稳定剂的PLGA纳米颗粒没有细胞毒性，但当用作纳米颗粒稳定剂时，轻微细胞毒性的CS聚合物赋予PLGA纳米颗粒显著的细胞毒性;更令人惊讶的是，其它无害的PVA和PF 68聚合物也赋予PLGA纳米颗粒显著的细胞毒性。这些结果揭示了用于配制PLGA纳米颗粒的稳定剂在高浓度下使用时所起的关键毒理学作用，这可能对基于PLGA的纳米药物的局部毒性有影响，并提供了内化纳米颗粒的细胞毒性作用的额外见解。(C)2014爱思唯尔有限公司版权所有。
The purpose of this study was to investigate the toxicity of a series of poly(lactide-co-glycolic) (PLGA) nanoparticles on human-like THP-1 macrophages. Positively-, negatively-charged and neutral nanoparticles (200 nm) were prepared using chitosan (CS), poloxamer 188 (PF68) and poly(vinyl alcohol) (PVA) as stabilizer. Stabilizer-free PLGA nanoparticles were obtained as well.When used at therapeutically relevant concentrations (up to 0.1 mg/mL in vitro), all tested nanoparticles showed no or scarce signs of toxicity, as assessed by cell mitochondrial activity, induction of apoptosis and necrosis, production of intracellular reactive oxygen species (ROS) and secretion of pro-inflammatory cytokines. At high concentrations (above 1 mg/mL), cytotoxicity was found to be induced by the presence of stabilizers, whatever the toxicological pattern of the stabilizer itself. While stabilizer-free PLGA nanoparticles exerted no cytotoxicity, the slightly cytotoxic CS polymer conferred PLGA nanoparticles significant cytotoxicity when used as nanoparticle stabilizer; more surprisingly, the otherwise innocuous PVA and PF68 polymers also conferred a significant cytotoxicity to PLGA nanoparticles.These results unveiled the critical toxicological contribution played by stabilizers used for the formulation of PLGA nanoparticles when used at high concentrations, which may have implications for local toxicities of PLGA-based nanomedicine, and provided additional insight in cytotoxic effects of internalized nanoparticles. (C) 2014 Elsevier B.V. All rights reserved.