Ultrashort Peptides-based Hydrogels Exposing Thiol Groups Forming Complexes with Peptide Nucleic Acid as Potential Tools for Smart Drug Release

Ultrashort aromatic peptide-based multicomponent hydrogels (HGs) have been used as biocompatible matrix for tissue engineering, drug delivery, and biosensor production. One of the most explored hydrogelators is the low molecular-weight Fmoc-FF (Nα-fluorenylmethoxycarbonyl-diphenylalanine) homodimer because of its ability to gel under physiological conditions such as of pH and ionic strength.1 Additional molecules, such as proteins, chemical compounds, or different peptide sequences, can be included into the Fmoc-FF hydrogel to create unique hydrogels with enhanced mechanical and functional characteristics. From this standpoint, a collection of unique multicomponent hydrogels based on Fmoc-FF that were doped with a range of concentrations of the tripeptide Fmoc-FFX, where X can be Cys, Ser, or Thr have been examined.2 Among these tripeptides, Fmoc-FFC was chosen as it generates hydrogels functionalized with thiol groups, which can be post-derived chemically with desirable bioactive compounds, such as biosensing, therapeutic or diagnostic agents. One of the most valuable nucleic acid mimetics is Peptide Nucleic Acid (PNA).3 Hybrid hydrogels are non-toxic and can serve as scaffolds for various applications in biotechnology, such as for controlled drug release in the presence of a reducing environment, such as the tumour microenvironment.4 In this regard, the functionalization of mixed (Cys)HG at different molar ratios compared to Fmoc-FF (1/5, 1/10 and 1/20, respectively) with (Cys)PNA molecules via specific and non-specific interactions is shown here, followed by the supramolecular characterization through several techniques, such as HPLC, MS, CD, FT-IR, NMR and microscopy.