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金纳米粒子与树枝状聚赖氨酸和叶酸靶向聚乙二醇偶联用于前列腺癌的 siRNA 递送。

Gold Nanoparticles Conjugated with Dendrigraft Poly-L-lysine and Folate-Targeted Poly(ethylene glycol) for siRNA Delivery to Prostate cancer.

机构信息

Department of Sciences, Faculty of Natural and Applied Sciences, Notre Dame University - Louaize, Lebanon.

Faculty of Sciences, Fanar Campus, Chemistry & Physics Department, and Doctoral School, Lebanese University, Beirut, Lebanon.

出版信息

Nanotheranostics. 2023 Jan 9;7(2):152-166. doi: 10.7150/ntno.79050. eCollection 2023.

DOI:10.7150/ntno.79050
PMID:36793347
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9925352/
Abstract

Dendrigraft Poly-L-Lysine (d-PLL) coated gold nanoparticles (AuNPs) were synthesized by reducing Tetrachloroauric acid with ascorbic acid in the presence of d-PLL. AuNPs-d-PLL formed a stable colloidal solution that absorbs light at a maximum wavelength (λ) centered at 570 nm as demonstrated by UV-visible (UV-Vis) spectroscopy. From Scanning Electron Microscopy (SEM) analysis, AuNPs-d-PLL were spherical in shape with a mean diameter of 128 ± 47 nm. Dynamic Light scattering (DLS) analysis of the colloidal solution exhibited one size distribution with a hydrodynamic diameter of about 131 nm (size distribution by intensity). Zeta potential (ξ) measurements revealed positively charged AuNPs-d-PLL with ξ about 32 mV, an indicator of high stability in an aqueous solution. The AuNPs-d-PLL was successfully modified with either thiolated poly (ethylene glycol) SH-PEG-OCH (M 5400 g mol) or folic acid-modified thiolated poly (ethylene glycol) SH-PEG-FA of similar molecular weight as demonstrated via DLS and Zeta potential measurements. Complexation of PEGylated AuNPs-d-PLL with siRNA was confirmed by DLS and gel electrophoresis. Finally, we analyzed the functionalization of our nanocomplexes with folic acid via targeted cellular uptake to prostate cancer cells using flow cytometry and LSM imaging. Our findings implicate the broader applicability of folate-PEGylated AuNPs in siRNA-based therapeutics against prostate cancer and perhaps other types of cancer.

摘要

树枝状聚赖氨酸(d-PLL)包裹的金纳米粒子(AuNPs)是通过在 d-PLL 的存在下用抗坏血酸还原四氯金酸合成的。AuNPs-d-PLL 形成了一种稳定的胶体溶液,在最大波长(λ)处吸收光,中心位于 570nm,如紫外可见(UV-Vis)光谱所示。从扫描电子显微镜(SEM)分析来看,AuNPs-d-PLL 呈球形,平均直径为 128±47nm。胶体溶液的动态光散射(DLS)分析显示,存在一个尺寸分布,水动力直径约为 131nm(强度分布)。ζ电位(ξ)测量显示,AuNPs-d-PLL 带正电荷,ξ约为 32mV,这表明在水溶液中具有很高的稳定性。AuNPs-d-PLL 成功地用巯基化聚乙二醇 SH-PEG-OCH(M 5400gmol)或叶酸修饰的巯基化聚乙二醇 SH-PEG-FA 修饰,这两种物质的分子量相似,如 DLS 和 ζ 电位测量所示。通过 DLS 和凝胶电泳证实了 PEG 化的 AuNPs-d-PLL 与 siRNA 的复合物形成。最后,我们通过流式细胞术和 LSM 成像分析了我们的纳米复合物通过靶向细胞摄取与叶酸的功能化,用于前列腺癌细胞。我们的研究结果表明,叶酸-PEG 化的 AuNPs 在基于 siRNA 的治疗前列腺癌和其他类型癌症方面具有更广泛的适用性。

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