title: Injected nanoparticles: the combination of experimental systems to assess cardiovascular adverse effects.
abstract: When nanocarriers are used for drug delivery they can often achieve superior therapeutic outcomes over standard drug formulations. However, concerns about their adverse effects are growing due to the association between exposure to certain nanosized particles and cardiovascular events. Here we examine the impact of intravenously injected drug-free nanocarriers on the cardiovasculature at both the systemic and organ levels. We combine in vivo and in vitro methods to enable monitoring of hemodynamic parameters in conscious rats, assessments of the function of the vessels after sub-chronic systemic exposure to nanocarriers and evaluation of the direct effect of nanocarriers on vascular tone. We demonstrate that nanocarriers can decrease blood pressure and increase heart rate in vivo via various mechanisms. Depending on the type, nanocarriers induce the dilation of the resistance arteries and/or change the responses induced by vasoconstrictor or vasodilator drugs. No direct correlation between physicochemical properties and cardiovascular effects of nanoparticles was observed. The proposed combination of methods empowers the studies of cardiovascular adverse effects of the nanocarriers.
authors: School of Pharmacy, University of Eastern Finland, Kuopio, Finland. Electronic address: maria.vlasova@uef.fi.
authors: Maria A
authors: MA
authors: Vlasova
authors: Department of Human and Animal Physiology, M.V. Lomonosov Moscow State University, Moscow, Russia; State Research Center of the Russian Federation, Institute for Biomedical Problems RAS, Moscow, Russia. Electronic address: ost.msu@gmail.com.
authors: Olga S
authors: OS
authors: Tarasova
authors: Department of Applied Physics, University of Eastern Finland, Kuopio, Finland. Electronic address: joakim.riikonen@uef.fi.
authors: Joakim
authors: J
authors: Riikonen
authors: Department of Applied Physics, Aalto University School of Science, Aalto, Finland. Electronic address: janne.raula@tkk.fi.
authors: Janne
authors: J
authors: Raula
authors: Institute of Problems of Chemical Physics, Russian Academy of Science, Moscow Region, Russia. Electronic address: lobach@icp.ac.ru.
authors: Anatoly S
authors: AS
authors: Lobach
authors: State Research Center of the Russian Federation, Institute for Biomedical Problems RAS, Moscow, Russia. Electronic address: borzykh.anna@gmail.com.
authors: Anna A
authors: AA
authors: Borzykh
authors: Department of Biotechnology and Molecular Medicine, A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland. Electronic address: boris.smirin@uef.fi.
authors: Boris V
authors: BV
authors: Smirin
authors: Department of Applied Physics, Aalto University School of Science, Aalto, Finland. Electronic address: esko.kauppinen@tkk.fi.
authors: Esko I
authors: EI
authors: Kauppinen
authors: Russian Research Center "Kurchatov Institute", Moscow, Russia. Electronic address: eletskii@mail.ru.
authors: Alexander V
authors: AV
authors: Eletskii
authors: Institute of Biomedicine & Biocenter of Oulu, University of Oulu, Oulu, Finland; Department of Psychiatry, Kuopio University Hospital, Kuopio, Finland. Electronic address: karl-heinz.herzig@oulu.fi.
authors: Karl-Heinz
authors: KH
authors: Herzig
authors: Department of Physics and Astronomy, University of Turku, Turku, Finland. Electronic address: jarno.salonen@utu.fi.
authors: Jarno
authors: J
authors: Salonen
authors: Department of Biotechnology and Molecular Medicine, A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland. Electronic address: pasi.tavi@uef.fi.
authors: Pasi
authors: P
authors: Tavi
authors: Department of Applied Physics, University of Eastern Finland, Kuopio, Finland. Electronic address: vesa-pekka.lehto@uef.fi.
authors: Vesa-Pekka
authors: VP
authors: Lehto
authors: School of Pharmacy, University of Eastern Finland, Kuopio, Finland. Electronic address: kristiina.jarvinen@uef.fi.
authors: Kristiina
authors: K
authors: Järvinen
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D002320:Cardiovascular Physiological Phenomena / Q000187:drug effects*; D002319:Cardiovascular System / Q000187:drug effects*; D004730:Endothelium, Vascular / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D007275:Injections, Intravenous; D008297:Male; D053758:Nanoparticles / Q000008:administration & dosage / Q000009:adverse effects* / Q000737:chemistry; D037742:Nanotubes, Carbon / Q000009:adverse effects* / Q000737:chemistry; D010316:Particle Size; D011109:Polymethacrylic Acids / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry; D016062:Porosity; D017208:Rats, Wistar; D012825:Silicon / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry; D013499:Surface Properties; D014655:Vascular Resistance / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
chemical_list: D037742:Nanotubes, Carbon; D011109:Polymethacrylic Acids; C038300:methylmethacrylate-methacrylic acid copolymer; D012825:Silicon
keywords: Aorta ring; Blood pressure; Nanoparticles; Rat; Telemetry; Wire myography