Nanomedicine (Lond.) (Epub ahead of print) ISSN 1743-5889 part of Research Article 10.2217/nnm.15.103 © 2015 Future Medicine Ltd Aim: To investigate the influence of gold nanoparticle geometry on the biochemical response of Calu-3 epithelial cells. Materials & methods: Spherical, triangular and hexagonal gold nanoparticles (GNPs) were used. The GNP-cell interaction was assessed via atomic absorption spectroscopy (AAS) and transmission electron microscopy (TEM). The biochemical impact of GNPs was determined over 72 h at (0.0001–1 mg/ ml). Results: At 1 mg/ml, hexagonal GNPs reduced Calu-3 viability below 60%, showed increased reactive oxygen species production and higher expression of proapoptotic markers. A cell mass burden of 1:2:12 as well as number of GNPs per cell (2:1:3) was observed for spherical:triangular:hexagonal GNPs. Conclusion: These findings do not suggest a direct shape-toxicity effect. However, do highlight the contribution of shape towards the GNP-cell interaction which impacts upon their intracellular number, mass and volume dose. Keywords:฀ biocompatibility฀•฀caspases฀•฀Cathepsin-B฀•฀CD95฀(APO-1/Fas)฀•฀cell฀death฀•฀gold฀ nanoparticles฀•฀lung฀epithelial฀cells฀•฀nanoparticle฀shape฀•฀nanotoxicology฀•฀reactive฀oxygen฀ species฀ Due to their plasmonic properties, gold nanoparticles (GNPs) have been proposed as advantageous nanosized materials for use in the various diagnostic and therapeutic appli- cations, such as cell imaging, targeted drug delivery, thermal ablation, phototherapy [1–7] . To date, spherical GNPs have been proven as one of the most biocompatible NP models for biological-based applications [8–12] . Recently, it has been reported that the specific shape of GNPs can be exploited to advantageously tune these nanomaterials for any biomedi- cal application of choice [8,13] . Examples of such alternatively shaped GNPs being pro- duced include, amongst others, rods, trian- gles, hexagons, prisms, urchins, cubes and wires [11,14] . Triangular and hexagonal GNPs have been specifically reported as promising contrast agents for in vivo imaging applica- tions in place of the commonly used spherical GNPs [8,13,15] . The reason for this is the shift of the optical resonance of these differently shaped GNPs to the near-infrared region of the spectrum, which allows for a greater potential to penetrate deeper inside tissues without photobleaching [5,13,16] . Therefore, to envisage the use of these alternatively shaped GNPs within any poten- tial medical applications their biocompatibil- ity must be realized. In this regard, increased attention has recently been focused towards their cellular interaction [17] . Although it is well known that specific physicochemical characteristics (e.g., size, surface chemistry) of GNPs can indeed influence their cellular uptake and accumulation [10,18] , the ability for shape to play a significant role in their interaction of GNPs with mammalian cells in vitro is not fully understood. Many stud- ies have undertaken investigations into how differently shaped NPs may interact with, or be internalized by mammalian cells [19] , yet in order to fully comprehend the potential of alternatively shaped GNPs for biomedical applications, their biochemical impact must also be considered [20] . However, understand- Investigating the role of shape on the biological impact of gold nanoparticles in vitro Furong Tian ‡,1,2 , Martin JD Clift ‡,3 , Alan Casey 2 , Pablo del Pino 4 , Beatriz Pelaz 5 , João Conde 6 , Hugh J Byrne 2 , Barbara Rothen-Rutishauser 3 , Giovani Estrada 7 , Jesús M de la Fuente 8 & Tobias Stoeger* ,1 1 Comprehensive฀Pneumology฀Centre,฀ Institute฀of฀Lung฀Biology฀&฀Disease,฀ Helmholtz฀Zentrum฀München,฀ Neuherberg,฀Germany 2 Nanolab฀Research฀Centre,฀FOCAS฀ Research฀Institute,฀Dublin฀Institute฀of฀ Technology,฀Camden฀Row,฀Dublin,฀ Ireland 3 BioNanomaterials,฀Adolphe฀Merkle฀ Institute,฀University฀of฀Fribourg,฀ Switzerland 4 CIC฀biomaGUNE,฀San฀Sebastian,฀Spain 5 Fachbereich฀Physik,฀Philipps฀Universität฀ Marburg,฀Marburg,฀Germany 6 Massachusetts฀Institute฀of฀Technology,฀ Institute฀for฀Medical฀Engineering฀ &฀Science,฀Harvard-MIT฀Division฀for฀ Health฀Sciences฀&฀Technology,฀E25–449฀ Cambridge,฀MA,฀USA 7 Institute฀of฀Bioinformatics,฀Helmholtz฀ Zentrum฀München,฀Neuherberg,฀ Germany 8 Instituto฀de฀Ciencia฀de฀Materiales฀de฀ Aragon฀CSIC-Universidad฀de฀Zaragoza,฀ Spain *Author฀for฀correspondence:฀ tobias.stoeger@helmholtz-muenchen.de Authors฀contributed฀equally For reprint orders, please contact: reprints@futuremedicine.com