dc.description.abstract | Background: Cancer is one of the leading causes of death worldwide. Effective approaches to prevent, diagnose, and treat cancer efficiently are yet to be discovered. To treat cancer, increasing drug delivery to tumor microenvironment and decreasing unspecific cytotoxicity are of paramount importance. To this end, nanotechnology tools are utilized. Recently, dendrimers have found numerous applications in drug delivery for cancer treatment. The aims of this study were to synthesize and characterize Dendrimer-Rapamycin nanoparticle, and to use it, along with 3-Bromopyruvate, for the treatment of MCF7 cell line with the aim of evaluating the effects of these treatments on cell viability.
Materials & Methods: 3-Bromopyruvate (3BrP) and Rapamycin (Rapa) were used to inhibit cancer cell growth in MCF7 breast cancer cells. G5 PAMAM Dendrimers were used to load Rapamycin and synthesize Rapamycin-loaded dendrimer nanoparticles. To determine cell viability, five treatment groups were considered for the MTT assay, including 3BrP, Rapa, Rapaloaded Dendrimers (Dend-Rapa), 3BrP along with Rapa (3BrP+R), and 3BrP along with DendRapa (3BrP+D).
Results: In the physico-Chemical evaluations of the synthesized nanoparticle, DLS results showed size in the range of 57.12nm and surface charge as +17.03. FTIR results were in the expected range. Drug loading was 50% and encapsulation efficiency was 69%. inhibition of cancer cell growth in the 3BrP+R group followed a synergistic effect in all timeframes (24H, 48H, and 72H). However, 3BrP+D group indicated synergistic effect only in 72H timeframe.
Conclusion These data exhibited that loading Rapa in dendrimers would lead to slow release of the drug in the environment, and thus decrease in the synergistic effect in 24H in 3BrP+D group. However, the data exhibited cytotoxic effects for the same treatment group in the long run (72H) in a synergistic manner. Such drug release pattern could increase specificity in killing cancer cells and decrease side effects. Loading Rapa in dendrimers does not essentially increase synergistic effects, but it creates a release pattern which allows the drug to exert its cytotoxic effects while decreasing side effects. The novelty of this study included employing the aforementioned drug combination along with the use of dendrimers in drug delivery. | en_US |