A safe-by-design approach to the development of gold nanoboxes as carriers for internalization into cancer cells |
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Authors: | Dania Movia Valerie Gerard Ciaran Manus Maguire Namrata Jain Alan P. Bell Valeria Nicolosi Tiina O'Neill Dimitri Scholz Yurii Gun'ko Yuri Volkov Adriele Prina-Mello |
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Affiliation: | 1. Centre for Research on Adaptive Nanostructures and Nanodevices (CRANN), Trinity College Dublin, Dublin, Ireland;2. School of Medicine, Trinity College Dublin, Dublin, Ireland;3. School of Chemistry, Trinity College Dublin, Dublin, Ireland;4. Advanced Microscopy Laboratory, Trinity College Dublin, Dublin, Ireland;5. School of Physics, Trinity College Dublin, Dublin, Ireland;6. UCD Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, D4 Dublin, Ireland |
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Abstract: | Gold nanomaterials are currently raising a signi?cant interest for human welfare in the ?eld 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. |
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Keywords: | Gold nanoboxes Lung cancer barrier High content screening and He-ion microscopy Safe-by-design Tiered approach Three-dimensional culture |
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