A Multiparametric Evaluation of Quantum Dot Size and Surface-Grafted Peptide Density on Cellular Uptake and Cytotoxicity.,Bioconjugate Chemistry

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A Multiparametric Evaluation of Quantum Dot Size and Surface-Grafted Peptide Density on Cellular Uptake and Cytotoxicity.
Bioconjugate Chemistry ( IF 4.0 ) Pub Date : 2020-03-25 , DOI: 10.1021/acs.bioconjchem.0c00078
Christy Maksoudian ₁ , Stefaan J Soenen ₁ , Kimihiro Susumu ₂ , Eunkeu Oh , Igor L Medintz , Bella B Manshian ₁

Affiliation

Despite the progress in nanotechnology for biomedical applications, great efforts are still being employed in optimizing nanoparticle (NP) design parameters to improve functionality and minimize bionanotoxicity. In this study, we developed CdSe/CdS/ZnS core/shell/shell quantum dots (QDs) that are compact ligand-coated and surface-functionalized with an HIV-1-derived TAT cell-penetrating peptide (CPP) analog to improve both biocompatibility and cellular uptake. Multiparametric studies were performed in different mammalian and murine cell lines to compare the effects of varying QD size and number of surface CPPs on cellular uptake, viability, generation of reactive oxygen species, mitochondrial health, cell area, and autophagy. Our results showed that the number of cell-associated NPs and their respective toxicity are higher for the larger QDs. Meanwhile, increasing the number of surface CPPs also enhanced cellular uptake and induced cytotoxicity through the generation of mitoROS and autophagy. Thus, here we report the optimal size and surface CPP combinations for improved QD cellular uptake.

中文翻译：

量子点大小和表面嫁接的肽密度对细胞摄取和细胞毒性的多参数评估。

尽管用于生物医学应用的纳米技术取得了进步，但仍在优化纳米粒子（NP）设计参数以提高功能性和最小化生物安全性方面进行了巨大的努力。在这项研究中，我们开发了CdSe / CdS / ZnS核/壳/壳量子点（QDs），它们被紧密配体包覆并用HIV-1衍生的TAT细胞穿透肽（CPP）类似物进行表面功能化，以改善两者生物相容性和细胞摄取。在不同的哺乳动物和鼠类细胞系中进行了多参数研究，比较了QD大小和表面CPP数量的变化对细胞摄取，活力，活性氧生成，线粒体健康，细胞面积和自噬的影响。我们的结果表明，与细胞相关的NP的数量及其各自的毒性对于较大的QD而言较高。同时，增加表面CPP的数量还通过产生mitoROS和自噬来增强细胞摄取并诱导细胞毒性。因此，在这里我们报告了改善QD细胞摄取的最佳大小和表面CPP组合。

更新日期：2020-04-23

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