Cationic and amphiphilic peptide-based hydrogels with dual activities as anticancer and antibacterial agents

The emergence of peptide-based functional biomaterials is on the rise. To fulfil this purpose, a series of amphiphilic peptides, such as H₂N-X-Met-Phe-C₁₂H₂₅, where X = L-lysine (CP1), X = L-histidine (CP2), and X = L-leucine (CP3), have been designed, synthesised, purified and fully characterised. Herein, we reported peptide-based supramolecular hydrogels with antibacterial and anticancer activities. An attempt has been made to investigate the antibacterial properties of these peptide-based hydrogels against Gram-positive (S. aureus and B. subtilis) and Gram-negative (E. coli and P. aeruginosa) bacteria. Investigations show that the L-lysine containing gelator, CP1, is active against both Gram-positive and Gram-negative bacteria and the L-histidine containing gelator, CP2, selectively inhibits the growth of Gram-negative bacteria. Interestingly, the L-leucine containing gelator, CP3, does not show any antibacterial properties. Moreover, the L-lysine containing gelator exhibits the best potency. Generation of reactive oxygen species (ROS) is a probable way to damage the bacterial membrane. To explore the cytotoxic properties and to determine the efficacy of the synthesized compounds in inhibiting cell viability, a comprehensive investigation was performed using three distinct cell lines: MDA-MB-231 (human triple-negative breast cancer), MDA-MB-468 (human triple-negative breast cancer) and HEK 293 (human embryonic kidney). Remarkably, the results of our study revealed a substantial cytotoxic impact of these peptide gelators on the MDA-MB-231 and MDA-MB-468 cell lines in comparison to the HEK 293 cells. Caspase 3/7 activity is the possible mechanistic path to determine the apoptotic rates of the cell lines. This finding emphasizes the promising potential of these peptide-based gelators in targeting and suppressing the growth of human triple negative breast cancer cells, while showing non-cytotoxicity towards non-cancerous HEK 293 cells. In a nutshell, these peptide-based materials are coming to light as next generation biomaterials.