The interactions of nanoparticles with the soft surfaces of biological systems like cells play key roles in executing their biomedical functions and in toxicity. The discovery or design of new biomedical functions, or the prediction of the toxicological consequences of nanoparticles in vivo, first require knowledge of the interplay processes of the nanoparticles with the target cells. This article focusses on the cellular uptake, location and translocation, and any biological consequences, such as cytotoxicity, of the most widely studied and used nanoparticles, such as carbon-based nanoparticles, metallic nanoparticles, and quantum dots. The relevance of the size and shape, composition, charge, and surface chemistry of the nanoparticles in cells is considered. The intracellular uptake pathways of the nanoparticles and the cellular responses, with potential signaling pathways activated by nanoparticle interactions, are also discussed.

With the potential wide uses of nanoparticles such as carbon nanotubes in biomedical applications, and the growing concerns of nanotoxicity of these engineered nanoparticles, the importance of nanoparticle-protein interactions cannot be stressed enough. In this study, we use both experimental and theoretical approaches, including atomic force microscope images, fluorescence spectroscopy, CD, SDS-PAGE, and molecular dynamics simulations, to investigate the interactions of single-wall carbon nanotubes (SWCNTs) with human serum proteins, and find a competitive binding of these proteins with different adsorption capacity and packing modes. The π-π stacking interactions between SWCNTs and aromatic residues (Trp, Phe, Tyr) are found to play a critical role in determining their adsorption capacity. Additional cellular cytotoxicity assays, with human acute monocytic leukemia cell line and human umbilical vein endothelial cells, reveal that the competitive bindings of blood proteins on the SWCNT surface can greatly alter their cellular interaction pathways and result in much reduced cytotoxicity for these protein-coated SWCNTs, according to their respective adsorption capacity. These findings have shed light toward the design of safe carbon nanotube nanomaterials by comprehensive preconsideration of their interactions with human serum proteins.competitive adsorption | nanoparticle-protein corona | hydrophobic interactions | conformational flexibility C arbon nanotubes (CNTs) have a broad range of potential applications, including nanoelectronics (1), biosensors (2), biomolecular recognition devices and molecular transporters (3, 4), and cancer therapy and diagnoses (5-7), because of their extraordinary mechanical, electronic, optical, geometric, and biological properties. Both the pharmacological (8, 9) and toxicological (10-15) profiles of CNTs have attracted much attention in recent years. Nanomedicine provides a great potential in fighting many diseases but a global effort is much needed to safely translate laboratory innovations into clinic trials. Seven grand challenges have been proposed for this endeavor (16). CNTbased multimodality imaging and therapy have been proposed for a variety of medical applications, such as carriers for chemotherapeutic drugs (17, 18), Raman detection and imaging (19,20), photoacoustic imaging, and photothermal therapy of cancers (6, 21). Meanwhile, of equal importance there is the emerging field of nanotoxicology, which aims to address the biosafety of these engineered nanoparticles, in particular, how these nanoparticles interact with human proteins in vivo (22)(23)(24)(25).Many studies have been performed on the biological effects of carbon nanotubes, and the interactions between proteins and CNTs (nanoparticle-protein corona) are believed to play an important role in the biological effects of CNTs (26-28). For example, CNTs could bind with pulmonary surfactant proteins A and D and then lead to susceptibility of lung infection and emphysema in mice (29). When the functionalized CNTs w...