Gadolinium-Loaded Poly(N-vinylcaprolactam) Nanogels: Synthesis, Characterization, and Application for Enhanced Tumor MR Imaging

Abstract

We report the synthesis of poly(N-vinylcaprolactam) nanogels (PVCL NGs) loaded with gadolinium (Gd) for tumor MR imaging applications. The PVCL NGs were synthesized via precipitation polymerization using the monomer N-vinylcaprolactam (VCL), the comonomer acrylic acid (AAc), and the degradable cross-linker 3,9-divinyl-2,4,8,10-tetraoxaspiro-[5,5]-undecane (VOU) in aqueous solution, followed by covalently binding with 2,2',2″-(10-(4-((2-aminoethyl)amino)-1-carboxy-4-oxobutyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triyl) triacetic acid (NH-DOTA-GA)/Gd complexes. We show that the formed Gd-loaded PVCL NGs (PVCL-Gd NGs) having a size of 180.67 ± 11.04 nm are water dispersible, colloidally stable, uniform in size distribution, and noncytotoxic in a range of the studied concentrations. The PVCL-Gd NGs also display a r relaxivity (6.38-7.10 mM s), which is much higher than the clinically used Gd chelates. These properties afforded the use of the PVCL-Gd NGs as an effective positive contrast agent for enhanced MR imaging of cancer cells in vitro as well as a subcutaneous tumor model in vivo. Our study suggests that the developed PVCL-Gd NGs could be applied as a promising contrast agent for T-weighted MR imaging of diverse biosystems.

Amylose‐Coated Biohybrid Microgels by Phosphorylase‐Catalyzed Grafting‐From Polymerization

“…Aqueous microgels are crosslinked porous polymer networks with a spherical shape which form colloidally stable dispersions in water . Special attention has been paid to microgels based on N ‐vinylcaprolactam (VCL) during the last years, since these exhibit outstanding properties like a high biocompatibility and temperature‐responsive behavior . PVCL microgels show a volume phase transition at a temperature of 32 °C, being swollen at temperatures below while losing water and thus collapsing at temperatures above.…”

“…PVCL microgels show a volume phase transition at a temperature of 32 °C, being swollen at temperatures below while losing water and thus collapsing at temperatures above. Due to the unique properties of PVCL microgels, numerous applications in the biomedical field were developed in the last years, for example, the use of PVCL‐based microgels for drug release or as contrast agent in tumor magnetic resonance (MR) imaging after gadolinium loading …”

In Situ Growth and Size Regulation of Single Gold Nanoparticles in Composite Microgels

“…PVCL‐ and PNIPAAm‐based MGs are temperature sensitive and exhibit a volume phase transition temperature of about 32 °C in water, which is close to body temperature . The big advantage of PVCL in comparison to PNIPAAm is that it shows superior biocompatibility . Numerous other monomers and cross‐linkers are known for their integration in the polymer network, to define the chemical composition of the MGs and to introduce various functional groups .…”

Functional Microgels: Recent Advances in Their Biomedical Applications

“…To achieve higher sensitivity and reduced leakage of contrast agent under physiological conditions, Sun et al developed acrylic acid‐functionalized PVCL‐based microgels via precipitation polymerization . The microgels were loaded with 2,2′,2″‐(10‐(4‐((2‐ aminoethyl)amino)‐1‐carboxy‐4‐oxobutyl)‐1,4,7,10‐tetraazacyclododecane‐1,4,7‐ triyl) triacetic acid (NH 2 ‐DOTA‐GA)/Gd complexes by covalent binding to avoid the leakage.…”

“…b) MR SNR of HeLa cells treated with the PVCL–Gd complex nanogels – 0.1% at different Gd concentrations for 4 h. c) In vivo T 1 ‐weighted MR images of the nude mice bearing subcutaneous HeLa tumors before and at different time points postinjection of the PVCL–Gd complex nanogels – 0.1%. Adapted with permission . Copyright 2017, American Chemical Society.…”