TY - JOUR
T1 - In Vitro and In Vivo Assessment of Heart-Homing Porous Silicon Nanoparticles
AU - Almeida Ferreira, Monica Patricia
AU - Ranjan, Sanjeev
AU - Correia, Alexandra
AU - Mäkilä, Ermei
AU - Kinnunen, Sini Marketta
AU - Zhang, Hongbo
AU - Shahbazi, Mohammad-Ali
AU - Vingadas Almeida, Patrick
AU - Salonen, Jarno
AU - Ruskoaho, Heikki Juhani
AU - Airaksinen, Anu
AU - Hirvonen, Jouni Tapio
AU - Almeida Santos, Helder
PY - 2016/7
Y1 - 2016/7
N2 - Chronic heart failure, predominantly developed after myocardial infarction, is a leading cause of highmortality worldwide. As existing therapies have still limited success, natural and/or synthetic nanomaterialsare emerging alternatives for the therapy of heart diseases. Therefore, we aimed to functionalizeundecylenic acid thermally hydrocarbonized porous silicon nanoparticles (NPs) with differenttargeting 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-targetedNPs in vivo. The toxicity profiles of the NPs evaluated in the three heart-type cells showed low toxicity atconcentrations up to 50 mg/mL. Qualitative and quantitative cellular uptake revealed a significant increasein 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. Competitiveuptake studies in primary cardiomyocytes showed the internalization of ANP-modified NPs takes placevia the guanylate cyclase-A receptor. When a myocardial infarction rat model was induced by isoprenalineand the peptide-modified [111In]NPs administered intravenously, the targeting peptides, particularlypeptide 2, improved the NPs' accumulation in the heart up to 3.0-fold, at 10 min. This studyhighlights the potential of these peptide-modified nanosystems for future applications in heart diseases
AB - Chronic heart failure, predominantly developed after myocardial infarction, is a leading cause of highmortality worldwide. As existing therapies have still limited success, natural and/or synthetic nanomaterialsare emerging alternatives for the therapy of heart diseases. Therefore, we aimed to functionalizeundecylenic acid thermally hydrocarbonized porous silicon nanoparticles (NPs) with differenttargeting 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-targetedNPs in vivo. The toxicity profiles of the NPs evaluated in the three heart-type cells showed low toxicity atconcentrations up to 50 mg/mL. Qualitative and quantitative cellular uptake revealed a significant increasein 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. Competitiveuptake studies in primary cardiomyocytes showed the internalization of ANP-modified NPs takes placevia the guanylate cyclase-A receptor. When a myocardial infarction rat model was induced by isoprenalineand the peptide-modified [111In]NPs administered intravenously, the targeting peptides, particularlypeptide 2, improved the NPs' accumulation in the heart up to 3.0-fold, at 10 min. This studyhighlights the potential of these peptide-modified nanosystems for future applications in heart diseases
KW - 317 Pharmacy
KW - Porous silicon
KW - Nanoparticles
KW - Targeting peptides
KW - Myocardial infarction
KW - In vivo
KW - Heart
KW - 216 Materials engineering
KW - 221 Nano-technology
U2 - 10.1016/j.biomaterials.2016.03.046
DO - 10.1016/j.biomaterials.2016.03.046
M3 - Article
SN - 0142-9612
VL - 94
SP - 93
EP - 104
JO - Biomaterials
JF - Biomaterials
ER -