Echeverry-Rendón Mónica, Stančič Brina, Muizer Kirsten, Duque Valentina, Calderon Deanne Jennei, Echeverria Felix, Harmsen Martin C
IMDEA Materials Institute, C/Eric Kandel 2, Getafe, Madrid 28906, Spain.
University of Groningenn, University Medical Center Groningen, Department of Pathology and Medical Biology, Hanzeplein 1, EA11, NL-9713 GZ Groningen, The Netherlands.
ACS Omega. 2022 May 19;7(21):17528-17537. doi: 10.1021/acsomega.1c06515. eCollection 2022 May 31.
Magnesium-based nanoparticles have shown promise in regenerative therapies in orthopedics and the cardiovascular system. Here, we set out to assess the influence of differently functionalized Mg nanoparticles on the cellular players of wound healing, the first step in the process of tissue regeneration. First, we thoroughly addressed the physicochemical characteristics of magnesium hydroxide nanoparticles, which exhibited low colloidal stability and strong aggregation in cell culture media. To address this matter, magnesium hydroxide nanoparticles underwent surface functionalization by 3-aminopropyltriethoxysilane (APTES), resulting in excellent dispersible properties in ethanol and improved colloidal stability in physiological media. The latter was determined as a concentration- and time-dependent phenomenon. There were no significant effects on THP-1 macrophage viability up to 1.500 μg/mL APTES-coated magnesium hydroxide nanoparticles. Accordingly, increased media pH and Mg concentration, the nanoparticles dissociation products, had no adverse effects on their viability and morphology. HDF, ASCs, and PK84 exhibited the highest, and HUVECs, HPMECs, and THP-1 cells the lowest resistance toward nanoparticle toxic effects. In conclusion, the indicated high magnesium hydroxide nanoparticles biocompatibility suggests them a potential drug delivery vehicle for treating diseases like fibrosis or cancer. If delivered in a targeted manner, cytotoxic nanoparticles could be considered a potential localized and specific prevention strategy for treating highly prevalent diseases like fibrosis or cancer. Looking toward the possible clinical applications, accurate interpretation of in vitro cellular responses is the keystone for the relevant prediction of subsequent in vivo biological effects.
镁基纳米颗粒在骨科和心血管系统的再生治疗中显示出了前景。在此，我们着手评估不同功能化的镁纳米颗粒对伤口愈合细胞参与者的影响，伤口愈合是组织再生过程的第一步。首先，我们全面研究了氢氧化镁纳米颗粒的物理化学特性，其在细胞培养基中表现出低胶体稳定性和强烈聚集。为了解决这个问题，氢氧化镁纳米颗粒用3-氨丙基三乙氧基硅烷（APTES）进行了表面功能化，使其在乙醇中具有优异的分散性能，并在生理介质中提高了胶体稳定性。后者被确定为一种浓度和时间依赖性现象。高达1500μg/mL的APTES包覆氢氧化镁纳米颗粒对THP-1巨噬细胞活力没有显著影响。因此，纳米颗粒解离产物——培养基pH值和镁浓度的增加，对其活力和形态没有不利影响。人皮肤成纤维细胞（HDF）、脂肪干细胞（ASCs）和PK84对纳米颗粒毒性作用的抵抗力最高，而人脐静脉内皮细胞（HUVECs）、人肺微血管内皮细胞（HPMECs）和THP-1细胞的抵抗力最低。总之，上述氢氧化镁纳米颗粒的高生物相容性表明它们是治疗纤维化或癌症等疾病的潜在药物递送载体。如果以靶向方式递送，细胞毒性纳米颗粒可被视为治疗纤维化或癌症等高发性疾病的潜在局部和特异性预防策略。展望可能的临床应用，准确解释体外细胞反应是相关预测后续体内生物学效应的关键。
