Nisin and nisin-loaded nanoparticles: a cytotoxicity investigation

Abstract

Objective

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.

Significance

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.

Methods

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).

Results

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.

Conclusions

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

Keywords:

• Nisin
• cytotoxicity
• food preservative
• lantibiotics
• nanoparticles

Acknowledgments

T. Haider acknowledges the Indian Council of Medical Research (ICMR), New Delhi, for financial support as SRF funding (Grant number for T. Haider 45/7/2018-Nan/BMS). We also thank the Sophisticated Instrument Center of Dr. Harisingh Gour University, Sagar, India, for providing the instrumentation facility.

Author contributions

Tanweer Haider: Investigation, Formal analysis, Writing - Original Draft, Writing - Review & Editing, Conceptualization, Methodology, Validation, Software, Data Curation.

Vikas Pandey: Methodology, Software.

Chittaranjan Behera: Formal analysis, Methodology.

Pradeep Kumar: Methodology, Formal analysis, Software

Prem N. Gupta: Writing - Review & Editing, Resources, Supervision.

Vandana Soni: Conceptualization, Methodology, Validation, Investigation, Formal analysis, Writing - Original Draft, Writing - Review & Editing, Supervision, Project administration.

Disclosure statement

No potential conflict of interest was reported by the authors.

Data availability statement

Data and material are available upon request.

Additional information

Funding

Indian Council of Medical Research (ICMR), New Delhi, for financial support as SRF funding [Grant number for T. Haider 45/7/2018-Nan/BMS).