title: A safe-by-design approach to the development of gold nanoboxes as carriers for internalization into cancer cells.
abstract: Gold nanomaterials are currently raising a signiﬁcant interest for human welfare in the ﬁeld of clinical diagnosis, therapeutics for chronic pathologies, as well as of many other biomedical applications. In particular, gold nanomaterials are becoming a promising technology for developing novel approaches and treatments against widespread societal diseases such as cancer. In this study, we investigated the potential of proprietary gold nanoboxes (AuNBs) as carriers for their perspective translation into multifunctional, pre-clinical nano-enabled systems for personalized medicine approaches against lung cancer. A safe-by-design, tiered approach, with systematic tests conducted in the early phases on uncoated AuNBs and more focused testing on the coated, drug-loaded nanomaterial toward the end, was adopted. Our results showed that uncoated AuNBs could effectively penetrate into human lung adenocarcinoma (A549) cells when in simple (mono-cultures) or complex (co- and three-dimensional-cultures) in vitro microenvironments mimicking the alveolar region of human lungs. Uncoated AuNBs were biologically inert in A549 cells and demonstrated signs of biodegradability. Concurrently, preliminary data revealed that coated, drug-loaded AuNBs could efficiently deliver a chemotherapeutic agent to A549 cells, corroborating the hypothesis that AuNBs could be used in the future for the development of personalized nano-enabled systems for lung cancer treatment.
authors.affiliation: Centre for Research on Adaptive Nanostructures and Nanodevices (CRANN), Trinity College Dublin, Dublin, Ireland.
authors.forename: Dania
authors.initials: D
authors.lastname: Movia
authors.affiliation: Centre for Research on Adaptive Nanostructures and Nanodevices (CRANN), Trinity College Dublin, Dublin, Ireland; School of Chemistry, Trinity College Dublin, Dublin, Ireland.
authors.forename: Valerie
authors.initials: V
authors.lastname: Gerard
authors.affiliation: School of Medicine, Trinity College Dublin, Dublin, Ireland.
authors.forename: Ciaran Manus
authors.initials: CM
authors.lastname: Maguire
authors.affiliation: School of Medicine, Trinity College Dublin, Dublin, Ireland.
authors.forename: Namrata
authors.initials: N
authors.lastname: Jain
authors.affiliation: Advanced Microscopy Laboratory, Trinity College Dublin, Dublin, Ireland.
authors.forename: Alan P
authors.initials: AP
authors.lastname: Bell
authors.affiliation: Centre for Research on Adaptive Nanostructures and Nanodevices (CRANN), Trinity College Dublin, Dublin, Ireland; School of Chemistry, Trinity College Dublin, Dublin, Ireland; School of Physics, Trinity College Dublin, Dublin, Ireland.
authors.forename: Valeria
authors.initials: V
authors.lastname: Nicolosi
authors.affiliation: UCD Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, D4 Dublin, Ireland.
authors.forename: Tiina
authors.initials: T
authors.lastname: O'Neill
authors.affiliation: UCD Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, D4 Dublin, Ireland.
authors.forename: Dimitri
authors.initials: D
authors.lastname: Scholz
authors.affiliation: Centre for Research on Adaptive Nanostructures and Nanodevices (CRANN), Trinity College Dublin, Dublin, Ireland; School of Chemistry, Trinity College Dublin, Dublin, Ireland.
authors.forename: Yurii
authors.initials: Y
authors.lastname: Gun'ko
authors.affiliation: Centre for Research on Adaptive Nanostructures and Nanodevices (CRANN), Trinity College Dublin, Dublin, Ireland; School of Medicine, Trinity College Dublin, Dublin, Ireland.
authors.forename: Yuri
authors.initials: Y
authors.lastname: Volkov
authors.affiliation: Centre for Research on Adaptive Nanostructures and Nanodevices (CRANN), Trinity College Dublin, Dublin, Ireland; School of Medicine, Trinity College Dublin, Dublin, Ireland. Electronic address: prinamea@tcd.ie.
authors.forename: Adriele
authors.initials: A
authors.lastname: Prina-Mello
mesh_terms: D001672:Biocompatible Materials / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems / Q000379:methods*; D004705:Endocytosis; D005780:Gelatin / Q000737:chemistry; D006046:Gold / Q000737:chemistry* / Q000633:toxicity; D006801:Humans; D049329:Nanostructures / Q000737:chemistry* / Q000633:toxicity / Q000648:ultrastructure; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D013997:Time Factors
chemical_list: D001672:Biocompatible Materials; D004337:Drug Carriers; D006046:Gold; D005780:Gelatin
keywords: Gold nanoboxes; High content screening and He-ion microscopy; Lung cancer barrier; Safe-by-design; Three-dimensional culture; Tiered approach