Nanoparticles (NPs) produced from amphiphilic derivatives of poly-N-vinylpyrrolidone (Amph-PVP), composed of various molecular weight polymeric hydrophilic fragments linked into hydrophobic n-alkyl chains of varying lengths, were previously shown to exert excellent biocompatibility. Although routes of administration can be different, finally, most nanosystems enter the blood circulation or lymphatic vessels, and by this, they establish direct contact with endothelial cells. In this study, Amph-PVP NPs and fluorescently labeled Amph-PVP-based NPs, namely “PVP” NPs (Amph-PVP-NPs (6000 Da) unloaded) and “F”-NPs (Amph-PVP-NPs (6000 Da) loaded with fluorescent FITC), were synthesized to study Amph-PVP NPs interactions with HMEC-1 endothelial cells. PVP NPs were readily uptaken by HMEC-1 cells in a concentration-dependent manner, as demonstrated by immunofluorescence imaging. Upon uptake, the FITC dye was localized to the perinuclear region and cytoplasm of treated cells. The generation of lipopolysaccharide (LPS)-induced activated endothelium model revealed an increased uptake of PVPNPs, as shown by confocal microscopy. Both unloaded PVP NPs and F-NPs did not affect EC viability in the 0.01 to 0.066 mg/mL range. Furthermore, we focused on the potential immunological activation of HMEC-1 endothelial cells upon PVPNPs treatment by assessing the expression of their E-Selectin, ICAM-1, and VCAM-1 adhesion receptors. None of the adhesion molecules were affected by NP treatments of both activated by LPS and nonactivated HMEC-1 cells, at the utilized concentrations (p = NS). In this study, PVP (6000 Da) NPs were used to encapsulate indomethacin, a widely used anti-inflammatory drug. The synthesized drug carrier complex did not affect HMEC-1 cell growth and expression of E-selectin, ICAM-1, and VCAM-1 adhesion receptors. In summary, PVP-based NPs are safe for use on both basal and activated endothelium, which more accurately mimics pathological conditions. Amph-PVP NPs are a promising drug delivery system.

中文翻译：

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评估两亲性聚-N-乙烯基吡咯烷酮纳米颗粒与体外内皮细胞的生物相容性和抗炎药物的递送

由聚N-乙烯基吡咯烷酮 (Amph-PVP) 的两亲衍生物制成的纳米颗粒 (NP) ，由连接到疏水n的各种分子量的聚合物亲水片段组成不同长度的 - 烷基链，先前已被证明具有出色的生物相容性。虽然给药途径可能不同，但最后，大多数纳米系统进入血液循环或淋巴管，并由此与内皮细胞建立直接接触。在这项研究中，Amph-PVP NPs 和荧光标记的 Amph-PVP NPs，即“PVP”NPs（Amph-PVP-NPs（6000 Da）卸载）和“F”-NPs（Amph-PVP-NPs（6000 Da） ) 加载荧光 FITC)，合成以研究 Amph-PVP NPs 与 HMEC-1 内皮细胞的相互作用。PVP NPs 很容易被 HMEC-1 细胞以浓度依赖的方式吸收，正如免疫荧光成像所证明的那样。摄取后，FITC 染料定位于处理细胞的核周区域和细胞质。如共聚焦显微镜所示，脂多糖 (LPS) 诱导的活化内皮模型的产生表明 PVPNPs 的吸收增加。在 0.01 至 0.066 mg/mL 范围内，未加载的 PVP NP 和 F-NP 均不影响 EC 活力。此外，我们通过评估其 E-选择素、ICAM-1 和 VCAM-1 粘附受体的表达，专注于 HMEC-1 内皮细胞在 PVPNPs 治疗后的潜在免疫激活。在所使用的浓度 (p = NS) 下，没有任何粘附分子受到 LPS 激活和未激活的 HMEC-1 细胞的 NP 处理的影响。在这项研究中，PVP (6000 Da) NPs 被用于封装吲哚美辛，一种广泛使用的抗炎药。合成的药物载体复合物不影响 HMEC-1 细胞生长和 E-选择素、ICAM-1 和 VCAM-1 粘附受体的表达。总之，基于 PVP 的 NPs 可安全用于基底和激活的内皮，更准确地模拟病理条件。Amph-PVP NPs 是一种很有前景的药物递送系统。