Stabilization and Anticancer Enhancing Activity of the Peptide Nisin by Cyclodextrin-Based Nanosponges against Colon and Breast Cancer Cells

Abstract

The great variability of cancer types demands novel drugs with broad spectrum, this is the case of Nisin, a polycyclic antibacterial peptide that recently has been considered for prevention of cancer cells growth. As an accepted food additive, this drug would be very useful for intestinal cancers, but the peptide nature would make easier its degradation by digestion procedures. For that reason, the aim of present study to investigate the protective effect of two different β-cyclodextrin-based nanosponges (carbonyl diimidazole and pyromellitic dianhydride) and their anti-cancer enhancement effect of Nisin-Z encapsulated with against colon cancer cells (HT-29). To extend its possible use, a comparison with breast (MCF-7) cancer cell was carried out. The physicochemical properties, loading efficiency, and release kinetics of Nisin complex with nanosponges were studied. Then, tricin-SDS-PAGE electrophoresis was used to understand the effect of NSs on stability of Nisin-Z in the presence of gastric peptidase pepsin. In addition, the cytotoxicity and cell membrane damage of Nisin Z were evaluated by using the MTT and LDH assay, which was complemented via Annexin-V/ Propidium Iodide (PI) by using flowcytometry. CD-NS are able to complex Nisin-Z with an encapsulation efficiency around 90%. A protective effect of Nisin-Z complexed with CD-NSs was observed in presence of pepsin. An increase in the percentage of apoptotic cells was observed when the cancer cells were exposed to Nisin Z complexed with nanosponges. Interestingly, Nisin Z free and loaded on PMDA/CDI-NSs is more selectively toxic towards HT-29 cells than MCF-7 cancer cells. These results indicated that nanosponges might be good candidates to protect peptides and deliver drugs against intestinal cancers.

Cyclodextrin-Based Nanosponges as Perse Antimicrobial Agents Increase the Activity of Natural Antimicrobial Peptide Nisin

“…In this study, we used the same conditions to prepare the complexes. However, the results of our previous study relatively confirmed the complex formation between nisin Z and both nanosponges by SEM techniques while providing the clearest evidence regarding DLS results and the effect of both NSs to change the release profile of nisin Z [ 33 ], as is supported by different publications [ 43 , 44 ]. In this study, a DSC method was carried out to determine the complex formation, with unsuccessful results; for this reason, we carried out FTIR as another validation test, but the results were unclear ( Figure 1 A).…”

“…Our previous report [ 33 ] demonstrated the possibility of complexing nisin with nanosponges as an effective way to stabilize the peptide. Indeed, good encapsulation efficiency of 90% was found under optimized conditions.…”

“…Nisin Z, through the freeze-drying method, was loaded on β-CD (5 mM), and CD-based NSs in the calculated amount of nisin Z in a weight ratio of 1:4 (drug:β-CD NS), as previously described in the literature [ 33 ].…”

“…In contrast to the procedure in our previous article, in which the release profile of nisin Z was examined at physiological pH [ 33 ], in this study, the release was examined at an acidic pH (pH = 4) over 48 h at 37 °C. Then, the nisin-Z content in the buffer solution was determined by the Bradford assay, as previously presented [ 38 ].…”

“…Our recent study provided evidence for the remarkable anticancer activity of nisin Z loaded on PMDA-NSs and CDI-NSs in comparison to nisin-Z-free forms, acting against colon and breast cancer cell lines [ 33 ]. Moreover, as nisin Z is considered an antimicrobial peptide, the antimicrobial activity of nisin-Z-loaded NSs needs to be investigated.…”