A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä
In vitro and in vivo assessment of heart-homing porous silicon nanoparticles
Tekijät: Mónica P.A. Ferreira, Sanjeev Ranjan, Alexandra M.R. Correia, Ermei M. Mäkilä, Sini M. Kinnunen, Hongbo Zhang, Mohammad-Ali Shahbazi, Patrick V. Almeida, Jarno J. Salonen, Heikki J. Ruskoaho, Anu J. Airaksinen, Jouni T. Hirvonen, Hélder A. Santos
Kustantaja: ELSEVIER SCI LTD
Julkaisuvuosi: 2016
Journal: Biomaterials
Tietokannassa oleva lehden nimi: BIOMATERIALS
Lehden akronyymi: BIOMATERIALS
Vuosikerta: 94
Aloitussivu: 93
Lopetussivu: 104
Sivujen määrä: 12
ISSN: 0142-9612
DOI: https://doi.org/10.1016/j.biomaterials.2016.03.046
Tiivistelmä
Chronic heart failure, predominantly developed after myocardial infarction, is a leading cause of high mortality worldwide. As existing therapies have still limited success, natural and/or synthetic nano materials are emerging alternatives for the therapy of heart diseases. Therefore, we aimed to functionalize undecylenic acid thermally hydrocarbonized porous silicon nanoparticles (NPs) with different targeting peptides to improve the NP's accumulation in different cardiac cells (primary cardiomyocytes, non-myocytes, and H9c2 cardiomyoblasts), additionally to investigate the behavior of the heart-targeted NPs in vivo. The toxicity profiles of the NPs evaluated in the three heart-type cells showed low toxicity at concentrations up to 50 mu g/mL. Qualitative and quantitative cellular uptake revealed a significant increase in the accumulation of atrial natriuretic peptide (ANP)-modified NPs in primary cardiomyocytes, non-myocytes and H9c2 cells, and in hypoxic primary cardiomyocytes and non-myocytes. Competitive uptake studies in primary cardiomyocytes showed the internalization of ANP-modified NPs takes place via the guanylate cyclase-A receptor. When a myocardial infarction rat model was induced by isoprene aline and the peptide-modified [In-111]NPs administered intravenously, the targeting peptides, particularly peptide 2, improved the NPs' accumulation in the heart up to 3.0-fold, at 10 min. This study highlights the potential of these peptide-modified nanosystems for future applications in heart diseases. (C) 2016 Elsevier Ltd. All rights reserved.
Chronic heart failure, predominantly developed after myocardial infarction, is a leading cause of high mortality worldwide. As existing therapies have still limited success, natural and/or synthetic nano materials are emerging alternatives for the therapy of heart diseases. Therefore, we aimed to functionalize undecylenic acid thermally hydrocarbonized porous silicon nanoparticles (NPs) with different targeting peptides to improve the NP's accumulation in different cardiac cells (primary cardiomyocytes, non-myocytes, and H9c2 cardiomyoblasts), additionally to investigate the behavior of the heart-targeted NPs in vivo. The toxicity profiles of the NPs evaluated in the three heart-type cells showed low toxicity at concentrations up to 50 mu g/mL. Qualitative and quantitative cellular uptake revealed a significant increase in the accumulation of atrial natriuretic peptide (ANP)-modified NPs in primary cardiomyocytes, non-myocytes and H9c2 cells, and in hypoxic primary cardiomyocytes and non-myocytes. Competitive uptake studies in primary cardiomyocytes showed the internalization of ANP-modified NPs takes place via the guanylate cyclase-A receptor. When a myocardial infarction rat model was induced by isoprene aline and the peptide-modified [In-111]NPs administered intravenously, the targeting peptides, particularly peptide 2, improved the NPs' accumulation in the heart up to 3.0-fold, at 10 min. This study highlights the potential of these peptide-modified nanosystems for future applications in heart diseases. (C) 2016 Elsevier Ltd. All rights reserved.
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