Abstrakti
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
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
Alkuperäiskieli | englanti |
---|---|
Lehti | Biomaterials |
Vuosikerta | 94 |
Sivut | 93–104 |
Sivumäärä | 12 |
ISSN | 0142-9612 |
DOI - pysyväislinkit | |
Tila | Julkaistu - heinäk. 2016 |
OKM-julkaisutyyppi | A1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä, vertaisarvioitu |
Tieteenalat
- 317 Farmasia
- 216 Materiaalitekniikka
- 221 Nanoteknologia
Laitteet
-
In vivo small animal SPECT/CT Imaging Laboratory
J. Arturo Garcia Horsman (Johtaja)
Farmasian tiedekuntaLaitteistot/tilat: Laitteet