Metabolic Signatures of Surface-Modified Poly(lactic-co-glycolic acid) Nanoparticles in Differentiated THP-1 Cells Derived with Liquid Chromatography-Mass Spectrometry-based Metabolomics.
Metabolic Signatures of Surface-Modified Poly(lactic-co-glycolic acid) Nanoparticles in Differentiated THP-1 Cells Derived with Liquid Chromatography-Mass Spectrometry-based Metabolomics.
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DOI：
10.1021/acsomega.2c01660
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发表时间：
2022-08-23
期刊：
影响因子：
4.1
通讯作者：
Kim, Dong-Hyun
中科院分区：
文献类型：
--
作者：
Al-natour, Mohammad A.;Abdelrazig, Salah;Ghaemmaghami, Amir M.;Alexander, Cameron;Kim, Dong-Hyun
聚合物纳米颗粒（NPs）被广泛用于临床前药物递送研究，一些制剂现已进入临床。然而，许多纳米粒子在亚细胞水平的详细影响尚未得到充分研究。在这项研究中，我们使用分化的THP-1巨噬细胞作为模型，研究与使用具有不同表面涂层或缀合化学的聚（乳酸-羟基乙酸）（PLGA）纳米颗粒相关的代谢变化。对用普通、Pluronic（F-127、F-68和P-85）包被的和PEG-PLGA NP处理的分化的THP-1细胞的提取物（n = 6）和对照（未处理）进行基于液相色谱-质谱的代谢谱分析。进行主成分分析和正交偏最小二乘判别分析（OPLS-DA）结合单变量和途径分析，以鉴定与细胞暴露于NP相关的显著改变的代谢物和途径。与对照相比，研究中每个类别的OPLS-DA显示出明显的分离和聚类，交叉验证值R2和Q2 > 0.5。共有105种代谢物和脂质被发现在分化的THP-1细胞谱中由于NP暴露而显著改变，而超过20种代谢途径被发现受到影响。这些途径包括甘油磷脂、鞘脂、亚油酸、精氨酸和脯氨酸以及α-亚麻酸代谢。PLGA纳米颗粒被发现扰乱一些氨基酸代谢途径，并改变膜脂质在不同程度上。PLGA纳米颗粒对细胞的代谢作用与银氧化物纳米颗粒和其他无机纳米材料引起的代谢作用相当。然而，与Pluronic共聚物包被的PLGA和普通PLGA NP相比，PEG-PLGA NP表现出对细胞代谢的影响降低。
Polymeric nanoparticles (NPs) are widely used in preclinical drug delivery investigations, and some formulations are now in the clinic. However, the detailed effects of many NPs at the subcellular level have not been fully investigated. In this study, we used differentiated THP-1 macrophage cells, as a model, to investigate the metabolic changes associated with the use of poly (lactic-co-glycolic acid) (PLGA) NPs with different surface coating or conjugation chemistries. Liquid chromatography-mass spectrometry-based metabolic profiling was performed on the extracts (n = 6) of the differentiated THP-1 cells treated with plain, Pluronic (F-127, F-68, and P-85)-coated and PEG–PLGA NPs and control (no treatment). Principal component analysis and orthogonal partial least squares-discriminant analysis (OPLS-DA) in conjunction with univariate and pathway analyses were performed to identify significantly changed metabolites and pathways related to exposure of the cells to NPs. OPLS-DA of each class in the study compared to the control showed clear separation and clustering with cross-validation values of R2 and Q2 > 0.5. A total of 105 metabolites and lipids were found to be significantly altered in the differentiated THP-1 cell profiles due to the NP exposure, whereas more than 20 metabolic pathways were found to be affected. These pathways included glycerophospholipid, sphingolipid, linoleic acid, arginine and proline, and alpha-linolenic acid metabolisms. PLGA NPs were found to perturb some amino acid metabolic pathways and altered membrane lipids to a different degree. The metabolic effect of the PLGA NPs on the cells were comparable to those caused by silver oxide NPs and other inorganic nanomaterials. However, PEG–PLGA NPs demonstrated a reduced impact on the cellular metabolism compared to Pluronic copolymer-coated PLGA and plain PLGA NPs.
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10.1111/j.2517-6161.1995.tb02031.x
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