Biocompatibility and Therapeutic Potential of Cinnamoyl‐Diphenylalanine Dipeptide: A Double‐Edged Sword

This study evaluates cinnamoyl-diphenylalanine dipeptide (Cin-FF), a newly introduced gelator, for its antimicrobial efficacy, biocompatibility, and potential anticancer properties in solution and gel forms. We show that Cin-FF exhibits antibacterial efficacy in the gel phase (0.2%, w/v), particularly against Escherichia coli, Acinetobacter baumannii, Staphylococcus aureus, and Bacillus subtilis, attributed to its sustained release and high concentration. In contrast, the solution phase has limited antimicrobial effects, particularly at lower concentrations (0.01% and 0.001%, w/v). The cytotoxicity of Cin-FF was evaluated across five mammalian cell lines: BJ human fibroblasts, SH-SY5Y neuroblastoma cells, mouse embryonic fibroblasts (MEF), HeLa cervical cancer cells, and Vero monkey kidney epithelial cells. Higher concentrations in the solution (0.1%, w/v) and in the gel phase (0.2%, w/v) are notably cytotoxic, particularly in the gel form. Lower concentrations in the solution form (0.01% and 0.001%, w/v) initially supported cell viability but induced delayed cytotoxicity by Day 4. Importantly, Cin-FF demonstrated potent cytotoxic effects against cancerous cell lines (HeLa and SH-SY5Y), suggesting its potential as a localized anticancer therapy. While Cin-FF in gel form shows considerable potential for both antimicrobial and anticancer applications, its cytotoxicity toward the noncancerous cells underscores the need for careful dosage control, formulation strategies, and targeted delivery to optimize therapeutic efficacy while minimizing harm to healthy tissues. This paves the way for further development as a multifunctional therapeutic agent.