Hyaluronic Acid-Coated SPIONs with Attached Folic Acid as Potential T2 MRI Contrasts for Anticancer Therapies.

in ACS applied materials & interfaces by Martyna Kasprzyk, Gabriela Opiła, Alicja Hinz, Sylwia Stankiewicz, Monika Bzowska, Karol Wolski, Joanna Dulińska-Litewka, Janusz Przewoźnik, Czesław Kapusta, Anna Karewicz

TLDR

  • The study developed a dual-targeted MRI contrast agent using SPIONs coated with hyaluronic acid and modified with folic acid, which showed superior performance in MRI and targeted cancer cells with reduced viability.

Abstract

Superparamagnetic iron oxide nanoparticles (SPIONs) are known to be good MRI contrasts, but they have a high tendency to aggregate and their biocompatibility is limited. Hyaluronic acid is highly biocompatible, can provide SPION with colloidal stability, and interacts specifically with tumor cells through the CD44 receptor; therefore, it was used as a stabilizing layer. We successfully obtained SPION coated with hyaluronic acid and further functionalized it with folic acid to construct a dual-targeted system. The physicochemical properties of the nanoparticles were investigated using DLS/ELS, AFM, XRD, and ATR-FTIR. Their magnetic characterization was performed by magnetometry, Mössbauer spectroscopy,H NMR T1 and T2 measurements, and MRI. The nanoparticles' biocompatibility was verified on blood and hepatocytes, and their cytotoxicity was tested on glioma and adenocarcinoma cells using the MTT assay. The nanoparticles were spherical, colloidally stable, and had low dispersity. Their cores were formed by 7 nm crystallites of magnetite in its oxidized form, maghemite. Our SPIONs were superparamagnetic and could potentially serve as effective T2 contrasts for MRI. The performance of SPIONs modified with folic acid was superior to that observed for commercial contrasts. Our nanoparticles were also hemocompatible and were efficiently taken up by glioblastoma cancer cells. Folic acid-modified SPIONs could also reduce viability of tumor cells in a dose-dependent manner. Thus, the proposed system has potential application as both a diagnostic tool and a therapeutic agent for targeted anticancer therapies.

Overview

  • The study aimed to develop a dual-targeted MRI contrast agent using superparamagnetic iron oxide nanoparticles (SPIONs) coated with hyaluronic acid and further modified with folic acid.
  • The nanoparticles were characterized using various techniques, including DLS/ELS, AFM, XRD, and ATR-FTIR, to investigate their physicochemical properties.
  • The biocompatibility and cytotoxicity of the nanoparticles were tested on different cells, and their potential for both diagnostic and therapeutic applications was explored.

Comparative Analysis & Findings

  • The SPIONs were found to be spherical, colloidally stable, and had low dispersity, with cores formed by 7 nm crystallites of magnetite in its oxidized form, maghemite.
  • The nanoparticles were superparamagnetic and could potentially serve as effective T2 contrasts for MRI, with superior performance compared to commercial contrasts.
  • Folic acid-modified SPIONs were found to efficiently take up by glioblastoma cancer cells and reduce viability of tumor cells in a dose-dependent manner.

Implications and Future Directions

  • The proposed system has potential application as a diagnostic tool and therapeutic agent for targeted anticancer therapies.
  • Future studies could explore the use of this system in other cancer types and its potential for imaging and treatment of tumors in combination with other therapies.
  • Additionally, the biocompatibility and biodistribution of the nanoparticles could be further investigated to optimize their use as a therapeutic agent.
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