{Reference Type}: Journal Article {Title}: Crystallographic facet-dependent stress responses by polyhedral lead sulfide nanocrystals and the potential "safe-by-design" approach {Author}: Chang, Yun; Li, Kai; Feng, Yanlin; Liu, Ning; Cheng, Yan; Sun, Xiujuan; Feng, Yuqing; Li, Xi; Wu, Zhijian; Haiyuan, Zhang {Journal}: Nano Research {ISBN/ISSN}: 1998-0124 {Year}: 2016 {Volume}: 9 {Issue}: 12 {Pages}: 3812-3827 {DOI}: 10.1007/s12274-016-1251-2 {Keywords}: nanomaterials {Keywords}: toxicity {Keywords}: facet {Keywords}: metal dissolution {Keywords}: safe-by-design {Abstract}: The particular physicochemical properties of nanomaterials are able to elicit unique biological responses. The property activity relationship is usually established for in-depth understanding of toxicity mechanisms and designing safer nanomaterials. In this study, the toxic role of specific crystallographic facets of a series of polyhedral lead sulfide (PbS) nanocrystals, including truncated octahedrons, cuboctahedrons, truncated cubes, and cubes, was investigated in human bronchial epithelial cells (BEAS-2B) and murine alveolar macrophages (RAW 264.7) cells. {100} facets were found capable of triggering facet-dependent cellular oxidative stress and heavy metal stress responses, such as glutathione depletion, lipid peroxidation, reactive oxygen species (ROS) production, heme oxygenase-1 (HO-1) and metallothionein (MT) expression, and mitochondrial dysfunction, while {111} facets remained inert under biological conditions. The {100}-facet-dependent toxicity was ascribed to {100}-facet-dependent lead dissolution, while the low lead dissolution of {111} facets was due to the strong protection afforded by poly(vinyl pyrrolidone) during synthesis. Based on this facet-toxicity relationship, a "safe-by-design" strategy was designed to prevent lead dissolution from {100} facets through the formation of atomically thin lead-chloride adlayers, resulting in safer polyhedral PbS nanocrystals. {URL}: https://www.sciopen.com/article/10.1007/s12274-016-1251-2 {Language}: en