Delivery Order of Nanoconstructs Affects Intracellular Trafficking by Endosomes.
Delivery Order of Nanoconstructs Affects Intracellular Trafficking by Endosomes.
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纳米结构物的递送顺序影响内体的细胞内运输。
DOI：
10.1021/jacs.2c02276
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发表时间：
2022-03-30
影响因子：
15
通讯作者：
Odom, Teri W.
中科院分区：
文献类型：
--
作者：
Lee, Kwahun;Jung, Insub;Odom, Teri W.
本文报道了具有不同表面曲率的纳米颗粒（NP）结构的内体途径如何受到其递送顺序的影响。 CpG（胞嘧啶-磷酸-鸟嘌呤）缀合的尖刺和球形金纳米粒子与巨噬细胞的连续孵育导致核内体内边缘处的纳米结构比例不同。在球形纳米粒子之后应用尖刺纳米粒子加速了晚期内涵体的形成并导致更大的内涵体，并且球形纳米粒子被尖刺纳米粒子包围。相反，反向孵育顺序在较小的内体中产生了两种纳米结构形状的不对称分布。巨噬细胞内含较高比例的封闭球形纳米粒子，以及在内体边缘具有较大比例的尖刺与球形纳米粒子，可增强 Toll 样受体 (TLR) 9 的激活以及促炎细胞因子和趋化因子的分泌。我们的结果表明，囊泡靶向纳米结构的亚细胞运输受到其递送顺序和内体分布的影响。我们的研究还建立了一种使用传统电子显微镜纳米级监测细胞内治疗药物传递的新方法。
This paper reports how the endosomal pathways of nanoparticle (NP) constructs with different surface curvatures are affected by their order of delivery. Sequential incubation of CpG (cytosine-phosphate-guanine)-conjugated spiky and spherical gold NPs with macrophages resulted in different nanoconstruct ratios at the interior edges of endosomes. Spiky NPs applied after spherical NPs accelerated the formation of late-stage endosomes and resulted in larger endosomes, and the spherical NPs were enclosed by the spiky NPs. In contrast, the reverse incubation order produced an asymmetric distribution of the two nanoconstruct shapes in smaller endosomes. Macrophages with a higher proportion of the enclosed spherical NPs as well as a larger ratio of spiky to spherical NPs at the endosomal edge produced enhanced toll-like receptor (TLR) 9 activation and secretion of proinflammatory cytokines and chemokines. Our results indicate that the subcellular trafficking of targeting nanoconstructs by vesicles is affected both by their delivery order as well as endosomal distribution. Our study also establishes a new approach for nanoscale monitoring of intracellular therapeutics delivery with a conventional electron microscopy.
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