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涂覆有中性和带电聚乙二醇的金纳米星:体外生物相容性及其与SH-SY5Y神经母细胞瘤细胞相互作用的比较研究

Gold nanostars coated with neutral and charged polyethylene glycols: A comparative study of in-vitro biocompatibility and of their interaction with SH-SY5Y neuroblastoma cells.

作者信息

Pallavicini Piersandro, Cabrini Elisa, Cavallaro Gennara, Chirico Giuseppe, Collini Maddalena, D'Alfonso Laura, Dacarro Giacomo, Donà Alice, Marchesi Nicoletta, Milanese Chiara, Pascale Alessia, Sironi Laura, Taglietti Angelo

机构信息

Dipartimento di Chimica, Università di Pavia, Viale Taramelli, 12, 27100 Pavia, Italy.

Dipartimento di Chimica, Università di Pavia, Viale Taramelli, 12, 27100 Pavia, Italy.

出版信息

J Inorg Biochem. 2015 Oct;151:123-31. doi: 10.1016/j.jinorgbio.2015.05.002. Epub 2015 May 8.

Abstract

Gold nanostars (GNS) have been coated with four different polyethylene glycols (PEGs) equipped with a -SH function for grafting on the gold surface. These PEGs have different chain lengths with average MW=2000, 3000, 5000 and average number of -O-CH2-CH2 - units 44, 66, and 111, respectively. Two are neutral and two are terminated with -COOH and -NH2 functions, thus bearing negative and positive charges at physiological pH, thanks to the formation of carboxylate and ammonium groups. The negative charge of the GNS coated with PEG carboxylate has also been exploited to further coat the GNS with the PAH (polyallylamine hydrochloride) cationic polymer. Vitality tests have been carried out on SH-SY5Y cells treated with the five differently coated GNS for 4, 24, and 48 h, at Au concentrations ranging from 1.25 to 100 μg/mL. The same tests have been repeated with the pure PEGs and PAH. Excellent biocompatibility was found for all PEGs, independently on charge and chain length, both for coated GNS and for the pure polymers. On the contrary, poor biocompatibility was found for PAH overcoated GNS and for pure PAH, although the latter only at high concentrations. Exploiting the two-photon luminescence of GNS, we have found by confocal laser scanning microscopy that when GNS are coated with PEGs they do not enter SH-SY5Y cells, while when overcoated with PAH they massively penetrate into the cytoplasm. This causes cell death by dramatically changing cell morphology, as demonstrated also by atomic force microscopy.

摘要

金纳米星(GNS)已用四种不同的带有 -SH 官能团的聚乙二醇(PEG)进行包覆,以便接枝到金表面。这些 PEG 具有不同的链长,平均分子量分别为 2000、3000、5000,平均 -O-CH2-CH2 - 单元数分别为 44、66 和 111。其中两种是中性的,另外两种分别以 -COOH 和 -NH2 官能团终止,由于羧酸盐和铵基团的形成,在生理 pH 条件下分别带有负电荷和正电荷。用聚(烯丙胺盐酸盐)(PAH)阳离子聚合物进一步包覆带有 PEG 羧酸盐的 GNS 的负电荷也得到了利用。在用五种不同包覆的 GNS 处理 SH-SY5Y 细胞 4、24 和 48 小时后进行了活力测试,金浓度范围为 1.25 至 100 μg/mL。用纯 PEG 和 PAH 重复了相同的测试。发现所有 PEG 都具有出色的生物相容性,与电荷和链长无关,无论是包覆的 GNS 还是纯聚合物都是如此。相反,发现 PAH 包覆的 GNS 和纯 PAH 的生物相容性较差,尽管后者仅在高浓度时如此。利用 GNS 的双光子发光,我们通过共聚焦激光扫描显微镜发现,当 GNS 用 PEG 包覆时它们不会进入 SH-SY5Y 细胞,而当用 PAH 包覆时它们会大量渗透到细胞质中。这会通过显著改变细胞形态导致细胞死亡,原子力显微镜也证明了这一点。

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