体外评价 L-肽修饰的磁性脂质纳米粒作为鼻咽癌的靶向磁共振成像造影剂。

In vitro evaluation of the L-peptide modified magnetic lipid nanoparticles as targeted magnetic resonance imaging contrast agent for the nasopharyngeal cancer.

机构信息

1Biomedical Technology and Device Research Labs, Industrial Technology Research Institute, Hsinchu, Taiwan.

出版信息

J Biomater Appl. 2013 Nov;28(4):580-94. doi: 10.1177/0885328212466685. Epub 2012 Nov 22.

Abstract

The purpose of this study was to analyze the encapsulation of superparamagnetic iron oxide nanoparticles (SPION) by the lipid nanoparticle conjugated with the 12-mer peptides (RLLDTNRPLLPY, L-peptide), and the delivery of this complex into living cells. The lipid nanoparticles employed in this work were highly hydrophilic, stable, and contained poly(ethylene-glycol) for conjugation to the bioactive L-peptide. The particle sizes of two different magnetic lipid nanoparticles, L-peptide modified (LML) and non-L-peptide modified (ML), were both around 170 nm with a narrow range of size disparity. The transversal relaxivity, r2, for both LML and ML nanoparticles were found to be significantly higher than the longitudinal relaxivity r1 (r2/r1 > 20). The in vitro tumor cell targeting efficacy of the LML nanoparticles were evaluated and compared to the ML nanoparticles, upon observing cellular uptake of magnetic lipid nanoparticles by the nasopharyngeal carcinoma cells, which express cell surface specific protein for the L-peptide binding revealed. In the Prussian blue staining experiment, cells incubated with LML nanoparticles indicated much higher intracellular iron density than cells incubated with only the ML and SPION nanoparticles. In addition, the MTT assay showed the negligible cell cytotoxicity for LML, ML and SPION nanoparticles. The MR imaging studies demonstrate the better T2-weighted images for the LML-nanoparticle-loaded nasopharyngeal carcinoma cells than the ML- and SPION-loaded cells.

摘要

本研究旨在分析超顺磁性氧化铁纳米粒子(SPION)被与 12 个氨基酸肽(RLLDTNRPLLPY,L-肽)偶联的脂质纳米颗粒(LNP)包封,并将该复合物递送至活细胞中。本工作中使用的脂质纳米颗粒具有高度亲水性、稳定性,并含有聚乙二醇(PEG)以与生物活性 L-肽结合。两种不同磁性脂质纳米颗粒(L-肽修饰的 LML 和非 L-肽修饰的 ML)的粒径均约为 170nm,粒径差异范围较窄。发现 LML 和 ML 纳米颗粒的横向弛豫率 r2 明显高于纵向弛豫率 r1(r2/r1>20)。通过观察表达 L-肽结合特异性细胞表面蛋白的鼻咽癌细胞对磁性脂质纳米颗粒的细胞摄取,评估并比较了 LML 纳米颗粒的体外肿瘤细胞靶向效率与 ML 纳米颗粒。普鲁士蓝染色实验表明,与仅用 ML 和 SPION 纳米颗粒孵育的细胞相比,用 LML 纳米颗粒孵育的细胞具有更高的细胞内铁密度。此外,MTT 测定表明 LML、ML 和 SPION 纳米颗粒对细胞的细胞毒性可忽略不计。MR 成像研究表明,与 ML 和 SPION 纳米颗粒负载的鼻咽癌细胞相比,LML 纳米颗粒负载的鼻咽癌细胞的 T2 加权图像更好。

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