Sammanfattning

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 mg/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
Originalspråkengelska
TidskriftBiomaterials
Volym94
Sidor (från-till)93–104
Antal sidor12
ISSN0142-9612
DOI
StatusPublicerad - jul 2016
MoE-publikationstypA1 Tidskriftsartikel-refererad

Vetenskapsgrenar

  • 317 Farmaci
  • 216 Materialteknik
  • 221 Nanoteknologi

Citera det här

@article{da3e77ea7adc490fb85d3b2bb000a42d,
title = "In Vitro and In Vivo Assessment of Heart-Homing Porous Silicon Nanoparticles",
abstract = "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",
keywords = "317 Pharmacy, Porous silicon, Nanoparticles, Targeting peptides, Myocardial infarction, In vivo, Heart, 216 Materials engineering, 221 Nano-technology",
author = "{Almeida Ferreira}, {Monica Patricia} and Sanjeev Ranjan and Alexandra Correia and Ermei M{\"a}kil{\"a} and Kinnunen, {Sini Marketta} and Hongbo Zhang and Mohammad-Ali Shahbazi and {Vingadas Almeida}, Patrick and Jarno Salonen and Ruskoaho, {Heikki Juhani} and Anu Airaksinen and Hirvonen, {Jouni Tapio} and {Almeida Santos}, Helder",
year = "2016",
month = "7",
doi = "10.1016/j.biomaterials.2016.03.046",
language = "English",
volume = "94",
pages = "93–104",
journal = "Biomaterials",
issn = "0142-9612",
publisher = "ELSEVIER SCI IRELAND LTD",

}

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

UR - http://www.journals.elsevier.com/biomaterials/

U2 - 10.1016/j.biomaterials.2016.03.046

DO - 10.1016/j.biomaterials.2016.03.046

M3 - Article

VL - 94

SP - 93

EP - 104

JO - Biomaterials

JF - Biomaterials

SN - 0142-9612

ER -