文獻：Evaluation of the physicochemical properties and the biocompatibility of polyethylene glycol-conjugated gold nanoparticles: A formulation strategy for siRNA delivery

作者：Kamil Rahme a b c 1, Jianfeng Guo d 1, Justin D. Holmes a b, Caitriona M. O’Driscoll

文獻鏈接：https://www.sciencedirect.com/science/article/abs/pii/S092777651530148X

摘要：

Recently, the potential of gold nanoparticles (AuNPs) for transporting drugs, proteins and genetic materials has been demonstrated. Previously, our laboratory synthesised positively charged, surfactant-free AuNPs in water by the reduction of gold (III) chloride (AuCl3) using hydroxylamine hydrochloride (NH2OH·HCl) in the presence of l-cysteine methyl ester hydrochloride (HSCH2CH(NH2)COOCH3·HCl) as a capping agent. These AuNPs, which achieve higher cell viability in comparison to cetyl trimethyl ammonium bromide (CTAB, a surfactant)-capped counterparts, have demonstrated potential for siRNA delivery. However, it is well known that systemic administration of cationic delivery systems without biological stablising moieties causes non-specific binding with negatively charged serum proteins, resulting in particle aggregation and opsonisation. Consequently, highly stable AuNPs capped with l-cysteine methyl ester hydrochloride conjugated to poly(ethylene glycol) (PEG) were synthesised in this study. PEGylation enhanced the biocompatibility of the AuNPs by reducing toxicity in a range of cell types, by inhibiting interaction with serum proteins thus avoiding aggregation, and, by providing protection against degradation by nucleases. Moreover, these PEGylated AuNPs formed nanoparticles (NPs) with siRNA (which was first compacted with protamine), and had a diameter within the nanoscale range (～250 nm) and a near neutral surface charge (～10 mV). In the future a bifunctional PEG chain on the AuNPs (i.e., SH-PEG-NH2, SH-PEG-COOH) will be used to facilitate conjugation of a targeting ligand to enhance cell specific uptake.

金納米粒子（AuNP）在運輸藥物、蛋白質和遺傳物質方面的潛力得到了證實。以前，我們的實驗室在l-半胱氨酸甲酯鹽酸鹽（HSCH2CH（NH2）COOCH3·HCl）作為封端劑的存在下，使用鹽酸羥胺（NH2OH·HCl）還原氯化金（III）（AuCl3），在水中合成帶正電荷、無表面活性劑的AuNP。

與十六烷基三甲基溴化銨（CTAB，一種表面活性劑）封端的對應物相比，這些AuNP具有更高的細胞存活率，已經證明了siRNA遞送的潛力。

然而，沒有生物穩定部分的陽離子遞送系統的全身給藥會導致與帶負電荷的血清蛋白的非特異性結合，從而導致顆粒聚集和調理。因此，本研究合成了用與聚乙二醇（PEG）共軛的l-半胱氨酸甲酯鹽酸鹽封端的高度穩定的AuNP。

聚乙二醇化通過降低一系列細胞類型的毒性、抑制與血清蛋白的相互作用從而避免聚集，以及提供防止核酸酶降解的保護，增強了AuNP的生物相容性。

此外，這些聚乙二醇化的AuNP與siRNA（首先用魚精蛋白壓實）形成納米顆粒（NP），直徑在納米級范圍內（約250 nm），表面電荷接近中性（約10 mV）。未來，AuNP上的雙功能PEG鏈（即SH-PEG-NH2、SH-PEG-COOH）將用于促進靶向配體的偶聯，以增強細胞特異性攝取。

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