Directly observing intracellular nanoparticle formation with nanocomputed tomography.

Zhang, Miaomiao; Guan, Yong; Dang, Zheng; Zhang, Pinggen; Zheng, Zhen; Chen, Liang; Kuang, Wen; Wang, Chenchen et al. · Sci Adv · 2020

basic_science · Level V

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Abstract

Directly observing intracellular nanostructure formation remains challenging. In this work, using a rationally designed small-molecule 4-nitrobenzyl carbamate-Cys(SEt)-Asp-Asp-Phe(iodine)-2-cyano-benzothiazole (NBC-Iod-CBT), we directly observed intracellular nanoparticle formation with nanocomputed tomography (nano-CT). In vitro, upon glutathione reduction and nitroreductase (NTR) cleavage, NBC-Iod-CBT undergoes a CBT-Cys click condensation reaction to self-assemble nanoparticles Iod-CBT-NPs with an average linear absorption coefficient (LAC) value of 0.182 ± 0.078 μm<sup>-1</sup> to x-ray. Nano-CT imaging of the NBC-Iod-CBT-treated, NTR-overexpressing HeLa cells showed the existence of Iod-CBT-NPs in their cytoplasm with an average LAC value of 0.172 ± 0.032 μm<sup>-1</sup> We anticipate that our strategy could help people to deeply understand the formation mechanism of intracellular nanostructures in the near future.