In vitro and in vivo assessment of heart-homing porous silicon nanoparticles.
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 [(111)In]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.
Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, FI-00014 Helsinki, Finland. Electronic address: monica.ferreira@helsinki.fi.
Mónica P A
MP
Ferreira
Laboratory of Radiochemistry, Department of Chemistry, University of Helsinki, FI-00014 Helsinki, Finland.
Sanjeev
S
Ranjan
Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, FI-00014 Helsinki, Finland.
Alexandra M R
AM
Correia
Laboratory of Industrial Physics, Department of Physics and Astronomy, University of Turku, FI-20014 Turku, Finland.
Ermei M
EM
Mäkilä
Division of Pharmacology and Pharmacotherapy, Faculty of Pharmacy, University of Helsinki, FI-00014 Helsinki, Finland.
Sini M
SM
Kinnunen
Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, FI-00014 Helsinki, Finland; School of Applied Science and Engineering, Harvard University, 02138 Cambridge MA, USA.
Hongbo
H
Zhang
Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, FI-00014 Helsinki, Finland.
Mohammad-Ali
MA
Shahbazi
Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, FI-00014 Helsinki, Finland.
Patrick V
PV
Almeida
Laboratory of Industrial Physics, Department of Physics and Astronomy, University of Turku, FI-20014 Turku, Finland.
Jarno J
JJ
Salonen
Division of Pharmacology and Pharmacotherapy, Faculty of Pharmacy, University of Helsinki, FI-00014 Helsinki, Finland.
Heikki J
HJ
Ruskoaho
Laboratory of Radiochemistry, Department of Chemistry, University of Helsinki, FI-00014 Helsinki, Finland.
Anu J
AJ
Airaksinen
Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, FI-00014 Helsinki, Finland. Electronic address: jouni.hirvonen@helsinki.fi.
Jouni T
JT
Hirvonen
Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, FI-00014 Helsinki, Finland. Electronic address: helder.santos@helsinki.fi.
Hélder A
HA
Santos
D000327:Adsorption; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000378:metabolism; D001798:Blood Proteins / Q000378:metabolism; D002470:Cell Survival; D003102:Colloids; D006321:Heart / Q000502:physiology*; D006801:Humans; D008297:Male; D032383:Myocytes, Cardiac / Q000378:metabolism; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D010455:Peptides / Q000737:chemistry; D016062:Porosity; D017208:Rats, Wistar; D012825:Silicon / Q000737:chemistry*; D013696:Temperature; D015899:Tomography, Emission-Computed, Single-Photon; D014476:Undecylenic Acids / Q000737:chemistry
D001798:Blood Proteins; D003102:Colloids; D010455:Peptides; D014476:Undecylenic Acids; D009320:Atrial Natriuretic Factor; D012825:Silicon
Heart; In vivo; Myocardial infarction; Nanoparticles; Porous silicon; Targeting peptides