Biocompatibility of Gd-Loaded Chitosan-Hyaluronic Acid Nanogels as Contrast Agents for Magnetic Resonance Cancer Imaging

Abstract

Although the research on nanogels incorporating Gd chelates for theranostic applications has grown exponentially in recent years, knowledge about their biocompatibility is limited. We compared the biocompatibility of Gd-loaded hyaluronic acid-chitosan-based nanogels (GdCA⊂CS-TPP/HA) with two chitosan concentrations (2.5 and 1.5 mg·mL−1 respectively) using SVEC4-10 murine lymph node endothelial cells. The sulforhodamine B method and released lactate dehydrogenase (LDH) activity were used as cell viability tests. Reactive oxygen species (ROS), reduced glutathione (GSH) and malondialdehyde (MDA) were measured by spectrophotometric and fluorimetric methods. Nrf-2 protein expression was evaluated by Western blot analysis and genotoxicity by alkaline comet assay. After 24 h, the cells viability was not affected by all types and doses of nanogels. The increase of ROS induced a low decrease of GSH concentration and a time-dependent raise of MDA one was produced by citric GdDOTA⊂CS-TPP/HA with a chitosan concentration of 1.5 mg·mL−1, at the highest dose applied. None of the tested nanogels induced changes in Nrf-2 protein expression. A slight but significant genotoxic effect was caused only by citric GdDOTA⊂CS-TPP/HA where CS concentration was 1.5 mg·mL−1. Our results showed a better biocompatibility with lymph node endothelial cells for Gd-loaded hyaluronic acid-chitosan based nanogels with a concentration in chitosan of 2.5 mg·mL−1.

Peptide-Based Soft Hydrogels Modified with Gadolinium Complexes as MRI Contrast Agents

“…Commercial CAs show relaxivity values between 4 and 5 mM −1 s −1 at 20 MHz and 310 K. In the past few years, many efforts have been made to improve CAs performance in terms of relaxivity values, biodistribution profile, and clearance time. One of the proposed strategies is the employment of macromolecular (polymers [9,10] and dendrimers [11,12]) or supramolecular (micelles [13][14][15], liposomes [16,17], nanogels [18,19], nanotubes [20,21], and fibers [22,23]) nanostructures for the delivery of Gd(III)-CAs. Due to their size and to their slow reorientation time, each gadolinium complex embedded in the nanostructure has a relaxivity value 2-5-fold higher in respect of the values associated to classical low molecular weight Gd-complexes.…”

<p>Nanogel loaded with surfactant based nanovesicles for enhanced ocular delivery of acetazolamide</p>

“…The average particle size, polydispersity index (PDI), and zeta potential (ZP) were measured. Triplicate determinations for each formulation were carried out and the mean±SD was deduced 18…”

Systematic overview of soft materials as a novel frontier for MRI contrast agents

“…Very recently, Dinischiotu et al, in collaboration with Chuburu's group, thoroughly investigated the biocompatibility of these CH/TPP/HA nanogels prepared at two different concentrations of CH (2.5 and 1.5 mg mL À1 ) and loaded with Gd-DOTP or Gd-DOTA complexes. 80 Quantication of the gadolinium ions highlighted the better loading capability of the formulations containing 2.5 mg mL À1 of CH. The CH concentration, type of acid or gadolinium contrast agent did not affect the cell survival proles and the LDH release in SVEC4-10 murine lymph node endothelial cells.…”