Synthesis and characterization of Gd3+-loaded hyaluronic acid-polydopamine nanoparticles as a dual contrast agent for CT and MRI scans

Abstract

Magnetic resonance imaging and computed tomography (CT) suffer from low contrast sensitivity and potential toxicity of contrast agents. To overcome these limitations, we developed and tested a new class of dual contrast agents based on polydopamine nanoparticles (PDA-NPs) that are functionalized and targeted with hyaluronic acid (HA). These nanoparticles (NPs) are chelated with Gd³⁺ to provide suitable contrast. The targeted NPs were characterized through ultraviolet-visible spectroscopy (UV-vis), scanning electron microscopy (SEM), infrared Fourier transform (FTIR), and dynamic light scattering (DLS). The cytotoxicity was investigated on HEK293 cells using an MTT assay. The contrast property of synthesized Gd³⁺/PDA/HA was compared with Barium sulfate and Dotarem, as commercial contrast agents (CAs) for CT and MRI, respectively. The results illustrated that synthesized PDA-NPs have a spherical morphology and an average diameter of 72 nm. A distinct absorption peak around 280 nm in the UV-vis spectrum reported the self-polymerization of PDA-NPs. The HA coating on PDA-NPs was revealed through a shift in the FTIR peak of C=O from 1618 cm^-1 to 1635 cm^-1. The Gd³⁺ adsorption on PDA/HA-NPs was confirmed using an adsorption isotherm assay. The developed CA showed low in vitro toxicity (up to 158.98 µM), and created a similar contrast in MRI and CT when compared to the commercial agents. The r₁ value for PDA/HA/Gd³⁺ (6.5 (mg/ml)^-1 s^-1) was more than Dotarem (5.6 (mg/ml)^-1 s^-1) and the results of the hemolysis test showed that at concentrations of 2, 4, 6, and 10 mg/ml, the hemolysis rate of red blood cells is very low. Additionally, the results demonstrated that PDA/HA/Gd³⁺ could better target the CD₄₄⁺-expressing cancer cells than PDA/Gd³⁺. Thus, it can be concluded that lower doses of developed CA are needed to achieve similar contrast of Dotarem, and the developed CA has no safety concerns in terms of hemolysis. The stability of PDA/HA/Gd³⁺ has also been evaluated by ICP-OES, zeta potential, and DLS during 3 days, and the results suggested that Gd-HA NPs were stable.