In vitro and in vivo assessment of heart-homing porous silicon nanoparticles

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• 作者：Mó ; nica P.A. Ferreira^a ; ^{monica.ferreira@helsinki.fi" class="auth_mail" title="E-mail the corresponding author} ; Sanjeev Ranjan^b ; Alexandra M.R. Correia^a ; Ermei M. M&auml ; kil&auml ; ^c ; Sini M. Kinnunen^d ; Hongbo Zhang^a ; ^e ; Mohammad-Ali Shahbazi^a ; Patrick V. Almeida^a ; Jarno J. Salonen^c ; Heikki J. Ruskoaho^d ; Anu J. Airaksinen^b ; Jouni T. Hirvonen^a ; ^{jouni.hirvonen@helsinki.fi" class="auth_mail" title="E-mail the corresponding author} ; Hé ; lder A. Santos^a ; ^{helder.santos@helsinki.fi" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Porous silicon ; Nanoparticles ; Targeting peptides ; Myocardial infarction ; In vivo ; Heart
• 刊名：Biomaterials
• 出版年：2016
• 出版时间：July 2016
• 年：2016
• 卷：94
• 期：Complete
• 页码：93-104
• 全文大小：2012 K

文摘

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 nanomaterials 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 μg/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 isoprenaline and the peptide-modified [¹¹¹In]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.