Directly observing intracellular nanoparticle formation with nanocomputed tomography

Miaomiao Zhang; Yong Guan; Zheng Dang; Pinggen Zhang; Zhen Zheng; Liang Chen; Wen Kuang; Chenchen Wang; Gaolin Liang

doi:10.1126/sciadv.aba3190

Directly observing intracellular nanoparticle formation with nanocomputed tomography

Sci Adv. 2020 Oct 23;6(43):eaba3190. doi: 10.1126/sciadv.aba3190. Print 2020 Oct.

Authors

Miaomiao Zhang¹, Yong Guan², Zheng Dang², Pinggen Zhang³, Zhen Zheng¹, Liang Chen², Wen Kuang¹, Chenchen Wang¹, Gaolin Liang^{4

5}

Affiliations

¹ Hefei National Laboratory of Physical Sciences at Microscale, Department of Chemistry, University of Science and Technology of China, 96 Jinzhai Road, Hefei, Anhui 230026, China.
² National Synchrotron Radiation Laboratory, University of Science and Technology of China, 42 Hezuohua South Road, Hefei, Anhui 230029, China.
³ School of Life Sciences, University of Science and Technology of China, 443 Huangshan Road, Hefei, Anhui 230027, China.
⁴ Hefei National Laboratory of Physical Sciences at Microscale, Department of Chemistry, University of Science and Technology of China, 96 Jinzhai Road, Hefei, Anhui 230026, China. gliang@ustc.edu.cn.
⁵ State Key Laboratory of Bioelectronics, School of Biological Sciences and Medical Engineering, Southeast University, 2 Sipailou Road, Nanjing, Jiangsu 210096, China.

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^-1 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^-1 We anticipate that our strategy could help people to deeply understand the formation mechanism of intracellular nanostructures in the near future.

Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).

Publication types

Research Support, Non-U.S. Gov't