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首页> 外文期刊>RSC Advances >Surface-decorated nanoparticles clicked into nanoparticle clusters for oligonucleotide encapsulation
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Surface-decorated nanoparticles clicked into nanoparticle clusters for oligonucleotide encapsulation

机译：表面装饰的纳米颗粒点击纳米粒子簇，用于寡核苷酸包封

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Gold nanoparticles (AuNPs) are the predominant and representative metal nano-carriers used for the tumor-targeted delivery of therapeutics because they possess advantages such as biocompatibility, high drug loading efficiency, and enhanced accumulation at tumor sites via the size-dependent enhanced permeability and retention (EPR) effect. In this study, we designed an AuNP functionalized with block polymers comprising polyethylenimine and azide group-functionalized poly(ethyl glycol) for the electrostatic incorporation of cytosine–guanine oligonucleotide (CpG ODN) on the surface. The ODN-incorporated AuNPs were cross-linked to gold nanoparticle clusters (AuNCs) via click chemistry using a matrix metalloproteinase (MMP)-2 cleavable peptide linker modified with alkyne groups at both ends. In the presence of Cu( I ), azide groups and alkyne groups spontaneously cyclize to form a triazole ring with high fidelity and efficiency, and therefore allow single AuNPs to stack to larger AuNCs for increased EPR effect-mediated tumor targeting. ~(1) H-NMR and Fourier transform infrared spectroscopy revealed the successful synthesis of an azide–PEG-grafted branched polyethylenimine, and the size and morphology of AuNPs fabricated by the synthesized polymer were confirmed to be 4.02 ± 0.45 nm by field emission-transmission electron microscopy. Raman spectroscopy characterization demonstrated the introduction of azide groups on the surface of the synthesized AuNPs. Zeta-potential and gel-retardation analysis of CpG-loaded AuNPs indicated complete CpG sequestration by AuNPs when the CpG?:?AuNP weight ratio was higher than 1?:?2.5. The clustering process of the CpG-loaded AuNPs was monitored and was demonstrated to be dependent on the alkyne linker-to-AuNP ratio. Thus, the clicked AuNC can be tailored as a gene carrier where a high accumulation of therapeutics is required.
机译：金纳米颗粒（AUNP）是用于肿瘤靶向治疗剂的主要和代表性的金属纳米载体，因为它们具有诸如生物相容性，高药物负载效率，并且通过尺寸依赖性增强的渗透率和增强的肿瘤部位积累的优点保留（EPR）效应。在该研究中，我们设计了一种具有包含聚乙基和叠氮酰基官能化聚（乙基二醇）的嵌段聚合物官能化的AUNP，用于静电掺入表面上的胞嘧啶 - 鸟嘌呤寡核苷酸（CPG ODN）。通过在两端用炔烃基团改性的基质金属蛋白酶（MMP）-2可切割的肽连接物，通过点击化学与金纳米颗粒簇（Aunc）交联到金纳米颗粒簇（Aunc）的oUNP。在Cu（I）的存在下，叠氮基团和炔烃自发地环环化以形成具有高保真性和效率的三唑环，因此允许单个aUnps堆叠到较大的Auncs以增加EPR效应介导的肿瘤靶向。 〜（1）H-NMR和傅里叶变换红外光谱显示出成功合成叠氮化物 - PEG接枝的支化聚乙烯，并通过场发射确认由合成聚合物制造的AUNP的尺寸和形态为4.02±0.45nm-透射电子显微镜。拉曼光谱表征证明了在合成的AUNPS表面上引入叠氮基团。 CPG负载的AUNP的Zeta-POSILO和凝胶延迟分析表明CPG时的肛门血管完全被隔离？：？AUNP重量比高于1？：？2.5。监测CPG负载型AUNP的聚类过程，并证明了依赖于炔烃接头与AUNP比率。因此，点击的Aunc可以作为基因载体定制，其中需要高积累的治疗剂。

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