Alginate-coated magnetic nanoparticles for noninvasive MRI of extracellular calcium.
Nanoparticles (NPs) have great potential to increase the diagnostic capacity of many imaging modalities. MRI is currently regarded as the method of choice for the imaging of deep tissues, and metal ions, such as calcium ions (Ca(2+)), are essential ingredients for life. Despite the tremendous importance of Ca(2+) for the well-being of living systems, the noninvasive determination of the changes in Ca(2+) levels in general, and extracellular Ca(2+) levels in particular, in deep tissues remains a challenge. Here, we describe the preparation and contrast mechanism of a flexible easy to prepare and selective superparamagnetic iron oxide (SPIO) NPs for the noninvasive determination of changes in extracellular Ca(2+) levels using conventional MRI. We show that SPIO NPs coated with monodisperse and purified alginate, having a specific molecular weight, provide a tool to selectively determine Ca(2+) concentrations in the range of 250 µm to 2.5 mm, even in the presence of competitive ions. The alginate-coated magnetic NPs (MNPs) aggregate in the presence of Ca(2+) , which, in turn, affects the T2 relaxation of the water protons in their vicinity. The new alginate-coated SPIO NP formulations, which have no effect on cell viability for 24 h, allow the detection of Ca(2+) levels secreted from ischemic cell cultures and the qualitative examination of the change in extracellular Ca(2+) levels in vivo. These results demonstrate that alginate-coated MNPs can be used, at least qualitatively, as a platform for the noninvasive MRI determination of extracellular Ca(2+) levels in myriad in vitro and in vivo biomedical applications.
School of Chemistry, The Raymond and Beverly Sackler Faculty of Exact Sciences, Tel Aviv University, Tel Aviv, Israel.
Amnon
A
Bar-Shir
Liat
L
Avram
Shani
S
Yariv-Shoushan
Debbie
D
Anaby
Smadar
S
Cohen
Niva
N
Segev-Amzaleg
Dan
D
Frenkel
Ofer
O
Sadan
Daniel
D
Offen
Yoram
Y
Cohen
D000464:Alginates / Q000737:chemistry*; D000818:Animals; D002118:Calcium / Q000032:analysis*; D002470:Cell Survival; D020723:Glucuronic Acid / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D008027:Light; D008279:Magnetic Resonance Imaging / Q000379:methods*; D058185:Magnetite Nanoparticles / Q000737:chemistry*; D008297:Male; D008810:Mice, Inbred C57BL; D017208:Rats, Wistar; D012542:Scattering, Radiation; D012815:Signal Processing, Computer-Assisted; D013997:Time Factors; D014867:Water
D000464:Alginates; D006603:Hexuronic Acids; D058185:Magnetite Nanoparticles; D014867:Water; D020723:Glucuronic Acid; D002118:Calcium
MRI; alginates; calcium sensing; contrast agents; magnetic nanoparticles; molecular MRI