Cyclodextrin based Nanosponges increased the anticancer and antimicrobial properties of the natural peptide Nisin

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The considerable increase in of anticancer and antimicrobial drug resistance in the last years have created a difficult situation in the society. The classical drugs are decreasing its efficiency and the scientific community, among other strategies, are focused on developing novel drugs or increase the activity of existing ones. In this context, the polymer called Cyclodextrin based Nanosponge (CD-NS) is an interesting and multitasking material with relevant effects with drugs and nutraceuticals [1,2].
Using this material, the prof. Francesco Trotta group of the University of Turin have recently published two studies where the anticancer and antimicrobial properties of the peptide Nisin have been increased [3,4]. Two examples of beta-cyclodextrin (β-CD) carbonated NS made by carbonyldiimidazole (CDI) and pyromellitic anhydride (PMDA) with ratio 1:4 were used to complex Nisin. The characterization included FTIR, DSC, SEM, particle size and Z-potential distribution. Moreover, the complexation showed a slower release profile and a protection of the peptide in presence of pepsine. Then, the bioactivities were studied:
In the case of cancer [3], two different cell lines: breast and colon cancer cell lines were tested. The use of BCD-PYRO and βCD-CDI complexation enhanced the cytotoxicity of Nisin at the same concentration of drug, but only with statistical significance between both carriers in colon cancer cells. The study of the specific route of cell toxicity was carried out using flow cytometric and it occurred by apoptotic pathway, late apoptosis/necrosis for colon and early apoptotic for breast cancer.
The antimicrobial enhancement of Nisin loaded-NS was tested against Gram-positive (Staphylococcus aureus) and negative (Escherichia coli) bacteria [4]. As before, the bioactivity of the Nisin was significantly increased when the complexed form was used. An interesting point was the total viable counts (TVCs) obtained with coocked chicken meat: the values were considerably lower for 30 days in presence of complexes.
Remarkably, these works not only indicate a remarkable increase of bioactivity of complexes, but also demonstrate the multitasking capacity of CD-NS complexing macromolecules.


[1] Matencio, A., Hoti, G., Monfared, Y. K., Rezayat, A., Pedrazzo, A. R., Caldera, F., & Trotta, F. (2021). Cyclodextrin Monomers and Polymers for Drug Activity Enhancement. Polymers, 13(11), 1684.

[2] Krabicová, I., Appleton, S. L., Tannous, M., Hoti, G., Caldera, F., Rubin Pedrazzo, A., … & Trotta, F. (2020). History of cyclodextrin nanosponges. Polymers, 12(5), 1122.

[3] Khazaei Monfared, Y., Mahmoudian, M., Cecone, C., Caldera, F., Zakeri-Milani, P., Matencio, A., & Trotta, F. (2022). Stabilization and Anticancer Enhancing Activity of the Peptide Nisin by Cyclodextrin-Based Nanosponges against Colon and Breast Cancer Cells. Polymers, 14(3), 594.

[4] Khazaei Monfared, Y., Mahmoudian, M., Hoti, G., Caldera, F., López Nicolás, J. M., Zakeri-Milani, P., … & Trotta, F. (2022). Cyclodextrin-Based Nanosponges as Perse Antimicrobial Agents Increase the Activity of Natural Antimicrobial Peptide Nisin. Pharmaceutics, 14(3), 685.

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