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纳米颗粒性质对间充质干细胞携带和相互作用的影响。

Effects of Nanoparticle Properties on Kartogenin Delivery and Interactions with Mesenchymal Stem Cells.

机构信息

School of Engineering, Center for Biomedical Engineering, Institute for Molecular and Nanoscale Innovation, Brown University, 184 Hope Street, Providence, RI, USA.

Department of Chemistry, Brown University, 324 Brook Street, Providence, RI, USA.

出版信息

Ann Biomed Eng. 2020 Jul;48(7):2090-2102. doi: 10.1007/s10439-019-02430-x. Epub 2019 Dec 5.

Abstract

Clinical trials with mesenchymal stem cells (MSCs) have demonstrated potential to treat osteoarthritis, a debilitating disease that affects millions. However, these therapies are often less effective due to heterogeneous MSC differentiation. Kartogenin (KGN), a synthetic small molecule that induces chondrogenesis, has recently been explored to decrease this heterogeneity. KGN has been encapsulated in nanoparticles due to its hydrophobicity. To explore the effect of nanoparticle properties on KGN and MSC interactions, here we fabricated three nanoparticle formulations that vary in hydrophobicity, size, and surface charge using nanoprecipitation: KGN-loaded poly(lactic acid-co-glycolic acid) (PLGA) nanoparticles (hydrophobic surface, negative charge, ~ 167 nm), PLGA-poly(ethylene glycol) (PEG) nanoparticles (hydrophilic surface, positive charge, ~ 297 nm), and PLGA-PEG-hyaluronic acid (HA) nanoparticles (hydrophilic surface, negative charge, ~ 507 nm). We observed differences in KGN loading, release, and suspension stability, with the PLGA particles exhibiting ~ 50% drug loading and PLGA-PEG-HA particles releasing the most KGN. All nanoparticles were found to interact with MSCs with evidence of increased uptake in PLGA-PEG and PLGA-PEG-HA compared with surface association of PLGA particles. Over short times (~ 7 days), MSCs incubated with all KGN-loaded formulations exhibited a similar increase in sulfated glycosaminoglycans, characteristic of chondrogenic differentiation, compared with non-KGN loaded formulations.

摘要

临床试验表明间充质干细胞(MSCs)具有治疗骨关节炎的潜力,骨关节炎是一种影响数百万人的致残性疾病。然而,由于间充质干细胞分化的异质性,这些治疗方法往往效果较差。卡托金(KGN)是一种诱导软骨形成的合成小分子,最近被探索用于减少这种异质性。由于其疏水性,KGN 被包封在纳米颗粒中。为了研究纳米颗粒性质对 KGN 和 MSC 相互作用的影响,我们使用纳米沉淀法制备了三种在疏水性、大小和表面电荷方面不同的纳米颗粒制剂:载有 KGN 的聚(乳酸-共-乙醇酸)(PLGA)纳米颗粒(疏水性表面,负电荷,167nm)、PLGA-聚乙二醇(PEG)纳米颗粒(亲水性表面,正电荷,297nm)和 PLGA-PEG-透明质酸(HA)纳米颗粒(亲水性表面,负电荷,507nm)。我们观察到 KGN 负载、释放和悬浮稳定性存在差异,PLGA 颗粒的载药量约为 50%,PLGA-PEG-HA 颗粒释放的 KGN 最多。所有纳米颗粒都被发现与 MSCs 相互作用,与 PLGA 颗粒的表面结合相比,PLGA-PEG 和 PLGA-PEG-HA 中的细胞摄取量增加。在短时间内(7 天),与未加载 KGN 的制剂相比,所有加载 KGN 的制剂孵育的 MSC 中硫酸化糖胺聚糖的含量均增加,这是软骨分化的特征。

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