Magnetic Dehydrodipeptide-Based Self-Assembled Hydrogels for Theragnostic Applications

Abstract

Self-assembled peptide hydrogels have emerged in recent years as the new paradigm in biomaterials research. We have contributed to this field the development of hydrogels based on dehydrodipeptides N-capped with naproxen. The dehydrodipeptide hydrogels can be loaded with drugs, thus being potential nanocarriers for drug delivery. In this work novel dehydrodipeptides containing tyrosine and aspartic acid amino acid residues N-capped with naproxen and C-terminal dehydrophenylalanine were prepared and characterized. Superparamagnetic iron oxide nanoparticles (SPIONs) were incorporated into the dehydrodipeptide-based hydrogels and their effect on the self-assembly, structure and rheological and magnetic properties of the hydrogels was studied. Magnetic hydrogels, with incorporated SPIONs, displayed concentration-dependent T2-MRI contrast enhancement. Moreover, upon magnetic excitation (alternating magnetic field –AMF–) the SPIONs were able to generate a significant amount of heat. Hence, magnetic hyperthermia can be used as a remote trigger for release of drug cargos and SPIONs incorporated into the self-assembled dehydrodipeptide hydrogels.

Biological Evaluation of Naproxen–Dehydrodipeptide Conjugates with Self-Hydrogelation Capacity as Dual LOX/COX Inhibitors

“…Here, we report for the first time the anti-inflammatory and anti-cancer properties of conjugates 3-8 ( Figure 2). We had previously reported the anti-inflammatory properties of compounds 1 and 2, but no results related to their effect on cancer cells or proteasome inhibitory activity [23]. Some previous biological results for compounds 1 and 2 will be presented alongside the results for compounds 3-8, where they are considered useful for comparison purposes.…”

“…The chemical synthesis and characterisation data for the compounds 1-4, 7 and 8 have been described previously [17,18,23]. The synthesis and characterisation data for compounds 5 and 6 are described in articles submitted for publication.…”

“…Upon magnetic excitation, the SPIONs generate heat, which causes the hydrogel to undergo a gel-to-solution phase transition. This means that magnetic hyperthermia can potentially be used as a remote trigger for the temporally and spatially controlled release of contrast agents [23].…”

“…Alternatively, the conjugates could display novel pharmacological properties not associated with the naproxen moiety. In a preliminary study [23], compounds 1 and 2 ( Figure 2) showed a modest ability to inhibit lipopolysaccharide (LPS)-induced production of nitric oxide ( • NO) radicals (a biomarker for inflammation) in RAW 264.7 cells. These compounds were also tested in enzymatic assays for their ability to inhibit key enzymes in the inflammatory cascade.…”

“…Upon magnetic excitation, the SPIONs generate heat, which causes the hydrogel to undergo a gel-to-solution phase transition. This means that magnetic hyperthermia can potentially be used as a remote trigger for the temporally and spatially controlled release of contrast agents [23]. While our previous work has focused on the ability of the hydrogels to act as delivery agents for incorporated drugs or diagnostic agents, we have also been keen to investigate the potential of naproxen-dehydrodipeptide conjugates as therapeutic agents by themselves, with obvious added potential for highly targeted topical applications as hydrogels.…”