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评估多锚定糖缀合物功能化氧化铁纳米颗粒在正常人结肠细胞系CCD-18Co中的生物相容性。

Assessing the Biocompatibility of Multi-Anchored Glycoconjugate Functionalized Iron Oxide Nanoparticles in a Normal Human Colon Cell Line CCD-18Co.

作者信息

Raval Yash S, Samstag Anna, Taylor Cedric, Huang Guohui, Mefford Olin Thompson, Tzeng Tzuen-Rong Jeremy

机构信息

Department of Biological Sciences, Clemson University, Clemson, SC 29634, USA.

Department of Materials Science and Engineering, Clemson University, Clemson, SC 29634, USA.

出版信息

Nanomaterials (Basel). 2021 Sep 22;11(10):2465. doi: 10.3390/nano11102465.

Abstract

We have previously demonstrated that iron oxide nanoparticles with dopamine-anchored heterobifunctional polyethylene oxide (PEO) polymer, namely PEO-IONPs, and bio-functionalized with sialic-acid specific glycoconjugate moiety (Neu5Ac(α2-3)Gal(β1-4)-Glcβ-sp), namely GM3-IONPs, can be effectively used as antibacterial agents against target . In this study, we evaluated the biocompatibility of PEO-IONPs and GM3-IONPs in a normal human colon cell line CCD-18Co via measuring cell proliferation, membrane integrity, and intracellular adenosine triphosphate (ATP), glutathione GSH, dihydrorhodamine (DHR) 123, and caspase 3/7 levels. PEO-IONPs caused a significant decrease in cell viability at concentrations above 100 μg/mL whereas GM3-IONPs did not cause a significant decrease in cell viability even at the highest dose of 500 μg/mL. The ATP synthase activity of CCD-18Co was significantly diminished in the presence of PEO-IONPs but not GM3-IONPs. PEO-IONPs also compromised the membrane integrity of CCD-18Co. In contrast, cells exposed to GM3-IONPs showed significantly different cell morphology, but with no apparent membrane damage. The interaction of PEO-IONPs or GM3-IONPs with CCD-18Co resulted in a substantial decrease in the intracellular GSH levels in a time- and concentration-dependent manner. Conversely, levels of DHR-123 increased with IONP concentrations. Levels of caspase 3/7 proteins were found to be significantly elevated in cells exposed to PEO-IONPs. Based on the results, we assume GM3-IONPs to be biocompatible with CCD-18Co and could be further evaluated for selective killing of pathogens in vivo.

摘要

我们之前已经证明,具有多巴胺锚定的异双功能聚环氧乙烷(PEO)聚合物的氧化铁纳米颗粒,即PEO-IONPs,并用唾液酸特异性糖缀合物部分(Neu5Ac(α2-3)Gal(β1-4)-Glcβ-sp)进行生物功能化,即GM3-IONPs,可以有效地用作针对靶标的抗菌剂。在本研究中,我们通过测量细胞增殖、膜完整性以及细胞内三磷酸腺苷(ATP)、谷胱甘肽(GSH)、二氢罗丹明(DHR)123和半胱天冬酶3/7水平,评估了PEO-IONPs和GM3-IONPs在正常人结肠细胞系CCD-18Co中的生物相容性。当浓度高于100μg/mL时,PEO-IONPs导致细胞活力显著下降,而即使在最高剂量500μg/mL时,GM3-IONPs也未导致细胞活力显著下降。在存在PEO-IONPs的情况下,CCD-18Co的ATP合酶活性显著降低,但在存在GM3-IONPs时未降低。PEO-IONPs还损害了CCD-18Co的膜完整性。相比之下,暴露于GM3-IONPs的细胞显示出明显不同的细胞形态,但没有明显的膜损伤。PEO-IONPs或GM3-IONPs与CCD-18Co的相互作用导致细胞内GSH水平以时间和浓度依赖性方式大幅下降。相反,DHR-123的水平随着IONP浓度的增加而升高。在暴露于PEO-IONPs的细胞中,发现半胱天冬酶3/7蛋白水平显著升高。基于这些结果,我们认为GM3-IONPs与CCD-18Co具有生物相容性,并可进一步评估其在体内选择性杀死病原体的能力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/addc/8537094/99c2189b4b53/nanomaterials-11-02465-g001.jpg

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