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.
Highlights
The SEM images showed that Nisin-Z should be included in the CD-NSs due to the morphological changes, from irregular structure to regular sphere (Figure 1B–E)
Based on the results of this study, we can conclude that pyromellitic dianhydride (PMDA) and carbonyl diimidazole (CDI)-NSs polymeric particles are able to carry Nisin Z, a peptide drug
This non-toxic delivery system showed notable uptake into MCF-7 and HT-29 cell lines, and the higher toxicity and cell membrane damage were shown by Nisin-Z encapsulated with NSs as compared to that of free Nisin Z
Summary
Colon cancer caused nearly 881,000 deaths in 2018 [2]. To overcome this challenge, the research of novel broad spectrum drugs is one of the most promising alternatives. There has been reported the anti-cancer effect of food preservative and bacteriocin agent, Nisin [3,4,5], a polycyclic antibacterial peptide containing 34-amino acid with rarely amino acids, such as dehydroalanine (Dha), dehydrobutirine (Dhb), lanthionine (Lan), and methyl-lanthionine (Melan) [2]. Thermal stability and antibacterial activity of Nisin are related to these unusual amino acids [2,6,7]
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