Nisin and nisin-loaded nanoparticles: a cytotoxicity investigation

Nisin is an antibacterial peptide with anticancer properties, but the main drawback is its rapid enzymatic degradation and limited permeation across the cell membrane. This research aims to overcome these drawbacks by developing nisin-loaded nanoparticles (NPN) with improved cytotoxic effects.

PLGA nanoparticles are one of the most effective biodegradable and biocompatible drug delivery carriers. In the present study, nisin-loaded nanoparticles showed enhanced anticancer effects.

NPN was prepared by a double emulsion solvent evaporation method and characterized for different parameters. The cytotoxic investigation of NPN was carried out on various cell lines, including A549, SW-620, HT-29, PC-3, MDA-MB-231, MCF-7, MiaPaca-2, and fR2 by sulforhodamine B (SRB) assay. Mechanistic investigation of cellular cytotoxicity was performed by using bright-field microscopy, DAPI staining, intracellular reactive oxygen species (ROS), changes in mitochondrial membrane potential (ΔΨm), Western blotting and cellular uptake study. A comparative cytotoxicity study of nisin and NPN was performed on normal breast epithelial cells (fR2).

NPN showed spherical shape, 289.09 ± 3.63 nm particle size, and 63.37 ± 3.12% entrapment efficiency. NPN was more cytotoxic to the MDA-MB-231 cell line, showing higher nuclear fragmentation, ROS generation, depletion of ΔΨm, and enhanced intracellular uptake with apoptosis signs compared with nisin and with no cytotoxicity on normal cells.

The findings suggest that nisin delivery via PLGA nanoparticles can be used to treat cancer without significant effects on healthy cells.