Direct immobilization of manganese chelates on silica nanospheres for MRI applications.
The development of tissue specific magnetic resonance imaging (MRI) contrast agents (CAs) is very desirable to achieve high contrast ratio combined with excellent anatomical details. To this end, we introduce a highly effective manganese(II) containing silica material, with the aim to shorten the longitudinal (T1) relaxation time. The microporous silica nanospheres (MSNSs) with enlarged porosity and specific surface area were prepared by a surfactant assisted aqueous method. Subsequently, the surface silanol groups were amino-functionalized, reacted with diethylenetriaminepentaacetic (DTPA) dianhydride and finally deposited with Mn2+. After comprehensive characterization, the MRI properties of functionalized MSNSs were investigated. The resulting nanospheres demonstrated substantial contrast enhancement during the in vitro MRI investigations, which was also evidenced by significant contrast enhancement on T1-weighted MR images in vivo. Moreover, in vitro cytotoxicity assay of functionalized MSNSs on hepatocyte mono- and hepatocyte-Kuppfer cell co-cultures showed no significant decrease in cell viability. Our findings confirmed our hypothesis, that Mn2+-chelating MSNSs are appropriate candidates for liver-specific T1-weighted MRI CAs with high relaxivities (r1=7.18mM-1s-1).
Institute of Materials and Environmental Chemistry, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Magyar tudósok körútja 2, 1117 Budapest, Hungary.
Marcell
M
Pálmai
Institute of Materials and Environmental Chemistry, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Magyar tudósok körútja 2, 1117 Budapest, Hungary.
Adrienn
A
Pethő
Institute of Materials and Environmental Chemistry, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Magyar tudósok körútja 2, 1117 Budapest, Hungary; MTA-SE Molecular Biophysics Research Group, Tűzoltó utca 37-47, 1094 Budapest, Hungary.
Lívia Naszályi
LN
Nagy
Institute of Materials and Environmental Chemistry, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Magyar tudósok körútja 2, 1117 Budapest, Hungary.
Szilvia
S
Klébert
Institute of Materials and Environmental Chemistry, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Magyar tudósok körútja 2, 1117 Budapest, Hungary.
Zoltán
Z
May
Institute of Materials and Environmental Chemistry, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Magyar tudósok körútja 2, 1117 Budapest, Hungary.
Judith
J
Mihály
Institute of Materials and Environmental Chemistry, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Magyar tudósok körútja 2, 1117 Budapest, Hungary.
András
A
Wacha
Institute of Organic Chemistry, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Magyar tudósok körútja 2, 1117 Budapest, Hungary.
Katalin
K
Jemnitz
Institute of Organic Chemistry, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Magyar tudósok körútja 2, 1117 Budapest, Hungary.
Zsuzsanna
Z
Veres
Department of Biophysics and Radiation Biology, Semmelweis University, Tűzoltó utca 37-47, 1094 Budapest, Hungary.
Ildikó
I
Horváth
Department of Biophysics and Radiation Biology, Semmelweis University, Tűzoltó utca 37-47, 1094 Budapest, Hungary.
Krisztián
K
Szigeti
CROmed Translational Research Centers, Budapest, Hungary.
Domokos
D
Máthé
Institute of Materials and Environmental Chemistry, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Magyar tudósok körútja 2, 1117 Budapest, Hungary. Electronic address: varga.zoltan@ttk.mta.hu.
Zoltán
Z
Varga
D000588:Amines / Q000737:chemistry; D000818:Animals; D002460:Cell Line; D002470:Cell Survival; D002614:Chelating Agents / Q000737:chemistry*; D003287:Contrast Media / Q000737:chemistry*; D022781:Hepatocytes / Q000166:cytology; D006801:Humans; D008099:Liver / Q000000981:diagnostic imaging; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008345:Manganese / Q000737:chemistry*; D008810:Mice, Inbred C57BL; D054118:Nanospheres / Q000737:chemistry*; D010316:Particle Size; D004369:Pentetic Acid / Q000031:analogs & derivatives / Q000737:chemistry; D016062:Porosity; D017208:Rats, Wistar; D012822:Silicon Dioxide / Q000737:chemistry*; D013499:Surface Properties
D000588:Amines; D002614:Chelating Agents; D003287:Contrast Media; C060068:diethylenetriaminetetraacetic acid; D008345:Manganese; D012822:Silicon Dioxide; D004369:Pentetic Acid
DTPA; Manganese(II) chelate; Nanoparticulate MRI contrast agent; Silica nanospheres