Anticancer potency of nitric oxide-releasing liposomes

Autor: Mark H. Schoenfisch, Dakota J. Suchyta
Rok vydání: 2017
Předmět:
Zdroj: RSC Advances. 7:53236-53246
ISSN: 2046-2069
Popis: In this study, fast and slow nitric oxide (NO)-releasing liposomes (half-lives of 2.5 and >72 h, respectively) were prepared by encapsulation of N-propyl-1,3-propanediamine/NO (PAPA/NO) and diethylenetriamine/NO (DETA/NO), respectively, via reverse phase evaporation. The anticancer activity of the otherwise equivalent fast and slow NO-releasing systems was evaluated against several distinct pancreatic, colorectal, and breast cancer cell lines. The anticancer assays (via cytotoxicity) over 72 h revealed that the slower NO-releasing liposomes consistently required lower NO payloads (LD50 6 μg/mL) to elicit cytotoxicity. The mechanism of intracellular NO build-up in cancer cells was studied using confocal fluorescence microscopy and flow cytometry, the results of which indicated that a more gradual NO accumulation was characteristic of the slow NO-release system. Protein expression via Western blot analysis revealed that slower NO release resulted in more necrotic/apoptotic cells, while faster release reduced the number of mitotic cells to a greater extent. Overall, these studies demonstrate the potential of NO-releasing liposomes for anticancer therapy and highlight the significance of release kinetics (and NO payloads) required to induce cell death.
Databáze: OpenAIRE