Fate of Antibody-Targeted Ultrasmall Gold Nanoparticles in Cancer Cells after Receptor-Mediated Uptake.
Fate of Antibody-Targeted Ultrasmall Gold Nanoparticles in Cancer Cells after Receptor-Mediated Uptake.
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DOI：
10.1021/acsnano.0c08128
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发表时间：
2021-06-22
期刊：
影响因子：
17.1
通讯作者：
Sokolov KV
中科院分区：
文献类型：
--
作者：
Han S;Zal T;Sokolov KV
与较大的纳米颗粒相比，超小尺寸（小于10 nm）的纳米颗粒在生物医学应用中具有许多优势，包括更好的肿瘤内分布，改善的药代动力学（PK）和有效的身体清除率。当用生物相容性涂层和靶特异性抗体功能化时，超小纳米颗粒代表了一个有吸引力的临床翻译平台。虽然有大量的工作致力于PK和各种纳米粒子的生物学效应，但对功能化纳米粒子的不同组分在生物环境（例如活细胞）中的命运知之甚少。在这里，我们使用5 nm的金纳米粒子（AuNPs）的发光特性来研究与由聚乙二醇（PEG）涂层和表皮生长因子受体（EGFR）靶向抗体组成的有机层功能化的AuNPs的细胞内运输和命运。我们表明，细胞内摄取的目标5纳米金纳米粒子的结果在一个强大的双光子发光（TPL），其特征在于广泛的发射和非常短的寿命相比，荧光的纳米粒子共轭的荧光团标记的抗体的荧光，从而允许选择性成像这些组件使用TPL和双光子激发荧光寿命显微镜（2 P-FLIM）。我们的研究结果表明，纳米颗粒的涂层是从细胞内的颗粒表面分离，导致形成具有强TPL的纳米颗粒簇。此外，我们还观察到细胞内颗粒的金核心和抗体涂层的光学分辨空间分离。我们使用的数据从双光子显微镜，2 P-FLIM，电子显微镜，并在体外试验，提出了一个模型的功能化5纳米金纳米粒子与活细胞的相互作用。
Nanoparticles with ultrasmall sizes (less than 10 nm) offer many advantages in biomedical applications compared to their bigger counterparts, including better intratumoral distribution, improved pharmacokinetics (PK), and efficient body clearance. When functionalized with a biocompatible coating and a target-specific antibody, ultrasmall nanoparticles represent an attractive clinical translation platform. Although there is a tremendous body of work dedicated to PK and the biological effects of various nanoparticles, little is known about the fate of different components of functionalized nanoparticles in a biological environment such as in live cells. Here, we used luminescence properties of 5 nm gold nanoparticles (AuNPs) to study the intracellular trafficking and fate of the AuNPs functionalized with an organic layer consisting of a polyethylene glycol (PEG) coating and epidermal growth factor receptor (EGFR)-targeting antibody. We showed that intracellular uptake of the targeted 5 nm AuNPs results in a strong two-photon luminescence (TPL) that is characterized by broad emission and very short lifetimes compared to the fluorescence of the nanoparticle-conjugated fluorophore-tagged antibody, thereby allowing selective imaging of these components using TPL and two-photon excited fluorescence lifetime microscopy (2P-FLIM). Our results indicate that the nanoparticle’s coating is detached from the particle’s surface inside cells, leading to formation of nanoparticle clusters with a strong TPL. Furthermore, we observed an optically resolved spatial separation of the gold core and the antibody coating of the particles inside cells. We used data from two-photon microscopy, 2P-FLIM, electron microscopy, and in vitro assays to propose a model of interactions of functionalized 5 nm AuNPs with live cells.
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DOI：
10.1016/j.jconrel.2013.09.013
发表时间：
2013-12-28
期刊：
Journal of controlled release : official journal of the Controlled Release Society
影响因子：
--
作者：
Ernsting MJ;Murakami M;Roy A;Li SD
通讯作者：
Li SD
影响因子：
10.8
作者：
Durr, Nicholas J.;Larson, Timothy;Ben-Yakar, Adela
通讯作者：
Ben-Yakar, Adela
影响因子：
7.4
作者：
Haiss, Wolfgang;Thanh, Nguyen T. K.;Fernig, David G.
通讯作者：
Fernig, David G.
影响因子：
17.1
作者：
Au L;Zhang Q;Cobley CM;Gidding M;Schwartz AG;Chen J;Xia Y
通讯作者：
Xia Y
影响因子：
2.8
作者：
Cavigli, Lucia;Centi, Sonia;Pini, Roberto
通讯作者：
Pini, Roberto