Regulation of Cell Uptake and Cytotoxicity by Nanoparticle Core under the Controlled Shape, Size, and Surface Chemistries

Nanoparticle structural parameters, such as size, surface chemistry, and shape, are well-recognized parameters that affect biological activities of nanoparticles. However, whether the core material of a nanoparticle also plays a role remains unknown. To answer this long-standing question, we synthesized and investigated a comprehensive library of 36 nanoparticles with all combinations of three types of core materials (Au, Pt, and Pd), two sizes (6 and 26 nm), and each conjugated with one of six surface ligands of different hydrophobicity. Using this systematic approach, we were able to identify cellular perturbation specifically attributed to core, size, or surface ligand. We discovered that core materials exhibited a comparable regulatory ability as surface ligand on cellular ROS generation and cytotoxicity. Pt nanoparticles were much more hydrophilic and showed much less cell uptake compared to Au and Pd nanoparticles with identical size, shape, and surface ligands. Furthermore, diverse core materials also regulated levels of cellular redox activities, resulting in different cytotoxicity. Specifically, Pd nanoparticles significantly reduced cellular H2O2 and promoted cell survival, while Au nanoparticles with identical size, shape, and surface ligand induced higher cellular oxidative stress and cytotoxicity. Our results demonstrate that nanoparticle core material is as important as other structural parameters in nanoparticle–cell interactions, making it also a necessary consideration when designing nanomedicines.