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Synthesis and Characterization of Elongated-Shaped Silver Nanoparticles as a Biocompatible Anisotropic SERS Probe for Intracellular Imaging: Theoretical Modeling and Experimental Verification

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Quaresma, Pedro
Pereira, Eulália
Franco, Jaime
Pernia Leal, Manuel
García-Martín, Maria Luisa
Royo, José Luis
Pozo, David

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Progress in the field of biocompatible SERS nanoparticles has promising prospects for biomedical applications. In this work, we have developed a biocompatible Raman probe by combining anisotropic silver nanoparticles with the dye rhodamine 6G followed by subsequent coating with bovine serum albumin. This nanosystem presents strong SERS capabilities in the near infrared (NIR) with a very high (2.7 107) analytical enhancement factor. Theoretical calculations reveal the effects of the electromagnetic and chemical mechanisms in the observed SERS effect for this nanosystem. Finite element method (FEM) calculations showed a considerable near field enhancement in NIR. Using density functional quantum chemical calculations, the chemical enhancement mechanism of rhodamine 6G by interaction with the nanoparticles was probed, allowing us to calculate spectra that closely reproduce the experimental results. The nanosystem was tested in cell culture experiments, showing cell internalization and also proving to be completely biocompatible, as no cell death was observed. Using a NIR laser, SERS signals could be detected even from inside cells, proving the applicability of this nanosystem as a biocompatible SERS probe.

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This work was supported by the following grants: In Spain: P07-FQM-02595 (to CC), P10-FQM-06615 (to JMOM), P10-CTS-6928 (to DP) and PAIDI2020 Program (FQM319 to RFM and CTS677 to DP) from the Regional Ministry of Economy, Junta de Andalucía, Spain. PI-0070/2008 (to PZ) and PI-0068/2008 (to DP) from the Regional Ministry of Health, Junta de Andalucía, Spain. PI-14-1600 from the Spanish Ministry of Economy-Instituto de Salud Carlos III (to DP), and in Portugal: (a) Unidade de Ciências Biomoleculares Aplicadas-UCIBIO which is financed by Portuguese national funds from FCT/MEC (UID/Multi/04378/2013) and co-financed by the ERDF under the PT2020 Partnership Agreement (POCI-01-0145-FEDER-007728); (b) European Union (FEDER funds through COMPETE) and National Funds (FCT, Fundação para a Ciência e Tecnologia), under the Partnership Agreement PT2020 through project UID/QUI/50006/2013-POCI/01/0145/FEDER/007265 (LAQV/REQUIMTE), Programa Operacional Regional do Norte (ON.2 - O Novo Norte), under the Quadro de Referência Estratégico Nacional (QREN) and funded by Fundo Europeu de Desenvolvimento Regional NORTE-01-0145-FEDER-000011; and (c) Grants EXPL/CTM-NAN/0754/2013 and PTDC/CTM-NAN/2912/2014, and post-doctoral fellowship (SFRH/BPD/84018/2012) to PQ, all financed by Fundação para a Ciência e a Tecnologia, Portugal. Acknowledgments: The authors thank the Conservation and Restoration Department, FCT/UNL and LAQV, REQUIMTE for the use of the Jobin-Yvon Raman spectrometer. Special thanks to Maria Jesús Sayagues for TEM images and useful discussion. In remembrance of Jose Antonio Mejías Romero on the 10th anniversary of his death.

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Caro, C.; Quaresma, P.; Pereira, E.; Franco, J.; Pernia Leal, M.; García-Martín, M.L.; Royo, J.L.; Oliva-Montero, J.M.; Merkling, P.J.; Zaderenko, A.P.; et al. Synthesis and Characterization of Elongated-Shaped Silver Nanoparticles as a Biocompatible Anisotropic SERS Probe for Intracellular Imaging: Theoretical Modeling and Experimental Verification. Nanomaterials 2019, 9, 256. https://doi.org/10.3390/nano9020256

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