Block copolymer cross-linked nanoassemblies improve particle stability and biocompatibility of superparamagnetic iron oxide nanoparticles.
OBJECTIVE
To develop cross-linked nanoassemblies (CNAs) as carriers for superparamagnetic iron oxide nanoparticles (IONPs).


METHODS
Ferric and ferrous ions were co-precipitated inside core-shell type nanoparticles prepared by cross-linking poly(ethylene glycol)-poly(aspartate) block copolymers to prepare CNAs entrapping Fe(3)O(4) IONPs (CNA-IONPs). Particle stability and biocompatibility of CNA-IONPs were characterized in comparison to citrate-coated Fe(3)O(4) IONPs (Citrate-IONPs).


RESULTS
CNA-IONPs, approximately 30 nm in diameter, showed no precipitation in water, PBS, or a cell culture medium after 3 or 30 h, at 22, 37, and 43°C, and 1, 2.5, and 5 mg/mL, whereas Citrate-IONPs agglomerated rapidly (> 400 nm) in all aqueous media tested. No cytotoxicity was observed in a mouse brain endothelial-derived cell line (bEnd.3) exposed to CNA-IONPs up to 10 mg/mL for 30 h. Citrate-IONPs (> 0.05 mg/mL) reduced cell viability after 3 h. CNA-IONPs retained the superparamagnetic properties of entrapped IONPs, enhancing T2-weighted magnetic resonance images (MRI) at 0.02 mg/mL, and generating heat at a mild hyperthermic level (40 ~ 42°C) with an alternating magnetic field (AMF).


CONCLUSIONS
Compared to citric acid coating, CNAs with a cross-linked anionic core improved particle stability and biocompatibility of IONPs, which would be beneficial for future MRI and AMF-induced remote hyperthermia applications.
Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, Kentucky 40536, USA.
Mo
M
Dan
Daniel F
DF
Scott
Peter A
PA
Hardy
Robert J
RJ
Wydra
J Zach
JZ
Hilt
Robert A
RA
Yokel
Younsoo
Y
Bae
D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry* / Q000633:toxicity; D001921:Brain / Q000166:cytology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D011232:Chemical Precipitation; D002951:Citrates / Q000737:chemistry / Q000633:toxicity; D003432:Cross-Linking Reagents / Q000737:chemistry / Q000633:toxicity; D006358:Hot Temperature; D060526:Magnetic Fields; D008279:Magnetic Resonance Imaging; D058185:Magnetite Nanoparticles / Q000737:chemistry* / Q000633:toxicity; D051379:Mice; D010316:Particle Size; D010455:Peptides / Q000737:chemistry* / Q000633:toxicity; D011092:Polyethylene Glycols / Q000737:chemistry* / Q000633:toxicity
D001672:Biocompatible Materials; D002951:Citrates; D003432:Cross-Linking Reagents; D058185:Magnetite Nanoparticles; D010455:Peptides; C017645:polyaspartate; D011092:Polyethylene Glycols