Antimicrobial Peptide Papiliocin-Carbon Nanotube Hybrids: Potential Dual-Action Agents for Antimicrobial Activity and Apoptotic Cancer Cell Death.

The emerging threat of antibiotic-resistant pathogens and the limitations that conventional cancer chemotherapies display have created an urgent need for the development of innovative therapeutic strategies. Combining the pleiotropic biological roles of antimicrobial peptides (AMPs) and nanomaterials through their conjugation presents a promising possibility of targeting both microbial membranes and malignant cells. In the present study, we engineered a novel bioactive material by immobilizing the insect-derived AMP Papiliocin onto multi-walled-decorated with polyethylene-glycol-carbon nanotubes (PEG-MWCNTs) to prevent proteolytic degradation of the peptide and enhance its cellular delivery. Recombinant Papiliocin was cloned, heterologously expressed, purified and conjugated onto the PEG-MWCNT carrier. Successful expression and conjugation were validated via immunoblotting and Fourier transform infrared (FT-IR) spectroscopy, respectively. Further physicochemical characterization of the bionanocomposites was conducted using Dynamic Light Scattering (DLS) and Zeta potential measurements. Biologically, the biofunctionalized material exhibited potent, broad-spectrum antimicrobial activity both on Staphylococcus aureus and Escherichia coli, inhibiting almost 90% of the latter's growth, highlighting the bioconjugate's specific interactions with the Gram-negative pathogens' membranes. Furthermore, it significantly reduced biofilm formation in Candida albicans, as indicated by the TCP assay. In parallel with its antimicrobial effects, CNTs-PEG-Papiliocin significantly reduced cancer cell viability and induced apoptosis via the extrinsic apoptosis pathway in HeLa cells, a response assisted by efficient intracellular delivery. Notably, cytotoxicity assays demonstrated lesser cytotoxic effect against non-tumorigenic HaCaT cells relative to the cancerous cell line. Collectively, these findings indicate the Papiliocin-biofunctionalized CNTs as a versatile, dual-action therapeutic agent with potential for antimicrobial activity and anticancer mode of action.