In Vivo Positive Magnetic Resonance Imaging of Brain Cancer (U87MG) Using Folic Acid-Conjugated Polyacrylic Acid-Coated Ultrasmall Manganese Oxide Nanoparticles

Abstract

Ultrasmall nanoparticles are potential candidates for application as high-performance imaging agents. Herein, we present the synthesis and characterization of folic acid (FA)-conjugated polyacrylic acid (PAA)-coated MnO nanoparticles with an average particle diameter of 2.7 nm. FA conferred cancer-targeting ability, while PAA conferred good colloidal stability and low cellular cytotoxicity on the FA-PAA-coated MnO nanoparticles. Further, the nanoparticles exhibited a high relaxivity (r1) value of 9.3 s−1mM−1 (r2/r1 = 2.2). Their application potential as cancer-targeting T1 magnetic resonance imaging contrast agents was confirmed by their enhanced T1 contrast enhancements at the brain cancer (U87MG) site upon intravenous administration to mice tails.

Paramagnetic ultrasmall Ho2O3 and Tm2O3 nanoparticles: characterization of r2 values and in vivo T2 MR images at a 3.0 T MR field

“…The positive zeta potential of the PEGD250- and PEGD600-coated nanoparticles in slightly acidic suspension media (pH = 6.5–6.7) is due to partially protonated oxygens and carboxyl groups of PEGD, thus providing positive values and consistent with previous observations in PEGD600-coated Fe 3 O 4 nanoparticles, 49 whereas the negative zeta potential of the PAA1800-coated nanoparticles is due to numerous negative COO − groups of PAA1800 in basic suspension sample (pH = ∼9.0) and consistent with previous observations for nanoparticles grafted with numerous COO − group containing polymers. 35,50,51 The nanoparticle colloidal dispersions in aqueous media were confirmed via Tyndall effects, where laser light scattering was observed only for the nanoparticle suspension samples due to collisions between the nanoparticle colloids and laser light whereas it was not observed for triple-distilled water (Fig. 2e).…”

Mono and Multiple Tumor-Targeting Ligand-Coated Ultrasmall Gadolinium Oxide Nanoparticles: Enhanced Tumor Imaging and Blood Circulation

“…FA-PAA was first prepared as described previously ( Figure 1 a) [ 40 ]. To obtain FA-NH 2 -Boc, 0.9 mmol FA was dissolved in DMSO (15 mL) in a 100-mL three-neck round-bottom flask at 60 °C under N 2 flow with magnetic stirring.…”

Functionalized Lanthanide Oxide Nanoparticles for Tumor Targeting, Medical Imaging, and Therapy

“…Among the various methods currently available for the synthesis of ultrasmall Ln 2 O 3 nanoparticles, the synthesis in a polyol solvent is preferred for biomedical applications because ultrasmall nanoparticles are obtained (average particle diameter = 2.0 nm) and subsequent surface coating of the nanoparticles with hydrophilic and biocompatible ligands can be performed in one pot [17,31]. A general reaction scheme for the polyol synthesis is provided in Figure 1.…”

“…Various experimental techniques can be used to characterize the synthesized Ln 2 O 3 nanoparticles [17,31], as summarized in Table 1. The particle diameters, the hydrodynamic diameters of nanoparticles dispersed in water, and the crystal structure of the nanoparticles can be measured using a high-resolution transmission electron microscope (HRTEM) operating at high acceleration voltages (>200 kV), a dynamic light scattering (DLS) particle size analyzer, and a powder X-ray diffraction (XRD) spectrometer, respectively.…”

“…The accumulation amount and specificity to tumors can be enhanced by active targeting, which is commonly achieved by modifying contrast agents with tumor-targeting ligands that can selectively bind to receptors overexpressed on tumor-cell membranes. Such tumor-targeting ligands include small molecules, such as arginylglycylaspartic acids (Arg-Gly-Asp or RGDs) [27][28][29] and folic acid [30,31], peptides, such as chlorotoxin (CTX) [32,33], and biological molecules, such as antibodies [34]. Nanoparticles can provide a flexible platform to attach tumor-targeting ligands, thereby improving their specificity and effectiveness for tumor treatment.…”