Multidentate Block-Copolymer-Stabilized Ultrasmall Superparamagnetic Iron Oxide Nanoparticles with Enhanced Colloidal Stability for Magnetic Resonance Imaging

Abstract

Ultrasmall superparamagnetic iron oxide nanoparticles (USPIOs) with diameters <5 nm hold great promise as T1-positive contrast agents for in vivo magnetic resonance imaging. However, control of the surface chemistry of USPIOs to ensure individual colloidal USPIOs with a ligand monolayer and to impart biocompatibility and enhanced colloidal stability is essential for successful clinical applications. Herein, an effective and versatile strategy enabling the development of aqueous colloidal USPIOs stabilized with well-defined multidentate block copolymers (MDBCs) is reported. The multifunctional MDBCs are designed to consist of an anchoring block possessing pendant carboxylates as multidentate anchoring groups strongly bound to USPIO surfaces and a hydrophilic block having pendant hydrophilic oligo(ethylene oxide) chains to confer water dispersibility and biocompatibility. The surface of USPIOs is saturated with multiple anchoring groups of MDBCs, thus exhibiting excellent long-term colloidal stability as well as enhanced colloidal stability at biologically relevant electrolyte, pH, and temperature conditions. Furthermore, relaxometric properties as well as in vitro and in vivo MR imaging results demonstrate that the MDBC-stabilized USPIO colloids hold great potential as an effective T1 contrast agent.

Iron Oxide Based Nanoparticles for Multimodal Imaging and Magnetoresponsive Therapy

“…The MR relaxivities of nanoparticles with different sizes, ranging from 3 to 8 nm, are investigated to study how the core size affects the relaxivity. 93 Magnetic nanoparticles can be used either as T 1 contrast agents or as T 2 contrast agents depending on their properties. Furthermore, the MR contrast effect can be tuned by changing their core size, surface states including surface atoms and coating, composition, and assembly of multiple nanoparticles.…”

Chain Length Effect of the Multidentate Block Copolymer Strategy to Stabilize Ultrasmall Fe3O4 Nanoparticles

“…MDBC-MM was chosen in place of MDBC-LM as it provides a direct comparison to our previous study on MDBC-stabilized USNPs as in vivo MRI contrast agents. [30] An alkaline stock solution of LA (sodium salt of lactic acid, pH 8.4) was prepared and mixed with aqueous MDBC/USNPs containing 150 mm NaCl. Figure 5 shows the evolution of the diameter of three colloids over 120 hours at 37 8C.…”

“…[28][29][30] The other tunable block varies with components that can promote compatibility with end-use applications. As such, MDBC stabilization is a versatile strategy in that SNP surfaces can be easily tuned through copolymerization, as well as conveniently functionalized with (bio)molecules during the polymerization for active targeting and dual optical imaging and MRI.…”

Rapid Nucleation of Iron Oxide Nanoclusters in Aqueous Solution by Plasma Electrochemistry

“…This magnetic behavior largely explains the lower relaxometric properties of ferritin (ferrihydrite) at lower iron concentrations, compared to USPIOs of maghemite/magnetite ( Figure 7). 28,30,55,56 In fact, USPIOs are superparamagnetic; the smallest of these nanoparticles (core = 3−5 nm diameter), such as Supravist (SHU-555C), have a longitudinal relaxivity of r 1 = 10.7 mM −1 s −1 and r 2 /r 1 = 3.6. 29 More recently, PEGylated USPIOs of smaller core diameters than Supravist have shown lower r 1 (4.5−4.8 mM −1 s −1 ) and r 2 /r 1 ratios in the order of 3.4−6.1.…”