Real-time in vivo monitoring of magnetic nanoparticles in the bloodstream by AC biosusceptometry.
BACKGROUND
We introduce and demonstrate that the AC biosusceptometry (ACB) technique enables real-time monitoring of magnetic nanoparticles (MNPs) in the bloodstream. We present an ACB system as a simple, portable, versatile, non-invasive, and accessible tool to study pharmacokinetic parameters of MNPs, such as circulation time, in real time. We synthesized and monitored manganese doped iron oxide nanoparticles in the bloodstream of Wistar rats using two different injection protocols. Aiming towards a translational approach, we also simultaneously evaluated cardiovascular parameters, including mean arterial pressure, heart rate, and episodes of arrhythmia in order to secure the well-being of all animals.


RESULTS
We found that serial injections increased the circulation time compared with single injections. Immediately after each injection, we observed a transitory drop in arterial pressure, a small drop in heart rate, and no episodes of arrhythmia. Although some cardiovascular effects were observed, they were transitory and easily recovered in both protocols.


CONCLUSIONS
These results indicate that the ACB system may be a valuable tool for in vivo, real-time MNP monitoring that allows associations with other techniques, such as pulsatile arterial pressure and electrocardiogram recordings, helping ensuring the protocol safety, which is a fundamental step towards clinical applications.
Biosciences Institute of Botucatu, São Paulo State University, Botucatu, São Paulo, Brazil.
André G
AG
Próspero
Biosciences Institute of Botucatu, São Paulo State University, Botucatu, São Paulo, Brazil.
Caio C
CC
Quini
Physics Institute, Federal University of Goiás, Goiânia, Goiás, Brazil. abakuzis@ufg.br.|Instituto de Física-Universidade Federal de Goiás, Goiânia, GO, 74690-900, Brazil. abakuzis@ufg.br.
Andris F
http://orcid.org/0000-0003-3366-106X
AF
Bakuzis
Biosciences Institute of Botucatu, São Paulo State University, Botucatu, São Paulo, Brazil.
Patrícia
P
Fidelis-de-Oliveira
Biosciences Institute of Botucatu, São Paulo State University, Botucatu, São Paulo, Brazil.
Gustavo M
GM
Moretto
Biosciences Institute of Botucatu, São Paulo State University, Botucatu, São Paulo, Brazil.
Fábio P F
FP
Mello
Biosciences Institute of Botucatu, São Paulo State University, Botucatu, São Paulo, Brazil.
Marcos F F
MF
Calabresi
Biosciences Institute of Botucatu, São Paulo State University, Botucatu, São Paulo, Brazil.
Ronaldo V R
RV
Matos
Biosciences Institute of Botucatu, São Paulo State University, Botucatu, São Paulo, Brazil.
Ednaldo A
EA
Zandoná
Physics Institute, Federal University of Goiás, Goiânia, Goiás, Brazil.
Nícholas
N
Zufelato
Ribeirão Preto School of Medicine, São Paulo University, Ribeirão Prêto, São Paulo, Brazil.
Ricardo B
RB
Oliveira
Biosciences Institute of Botucatu, São Paulo State University, Botucatu, São Paulo, Brazil.
José R A
JR
Miranda
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced; D001776:Blood Circulation Time; D001794:Blood Pressure; D004562:Electrocardiography; D005290:Ferric Compounds / Q000097:blood* / Q000493:pharmacokinetics; D006339:Heart Rate; D008280:Magnetics; D058185:Magnetite Nanoparticles / Q000737:chemistry*; D060306:Magnetometry / Q000379:methods*; D008297:Male; D010316:Particle Size; D051381:Rats; D017208:Rats, Wistar
D005290:Ferric Compounds; D058185:Magnetite Nanoparticles; C000499:ferric oxide
AC biosusceptometry; Cardiovascular analysis; Circulation time; Magnetic nanoparticles; Pharmacokinetics