Examining the Anti-Tumor Activity of Dp44mT-Loaded Nanoparticles In Vitro

We have recently reported encapsulating an antitumor iron chelator, Dp44mT (Di-2-pyridylketone-4,4dimethyl-3-thiosemicarbazone), in nanoparticles (NPs) of poly(lactic-co-glycolic acid) (PLGA). In this paper, we examine the effectiveness of this nano-formulation, referred to as Dp44mT-NPs, against several cancer cell lines in vitro; specifically, we evaluate the cytotoxicity of this formulation in glioma (U87, U251), breast (MCF7), and colorectal (HT29) cancer cell lines. Cell viability results from treatment of glioma cells with Dp44mT-NPs for 24-72 hrs revealed that these NPs were highly toxic towards these malignant cells with very low IC
₅₀
values (<; 100 nM). Although addition of a PEG (poly(ethylene glycol)) layer to the surface of NPs reduced their toxicity in glioma cells, they remained highly toxic towards these cells (IC
₅₀
of 135-210 nM). Dp44mT-NPs were also toxic towards breast MCF7 and colorectal HT29 cells, but at higher dosages (IC
₅₀
>1 μM) compared to glioma cells. Addition of PEG to these NPs, again lowered their toxicity in these cells. Varying the percentage of PEG on NPs resulted in changes in their cytotoxicity, highlighting the necessity of further optimization of this parameter. This study, overall, demonstrates the therapeutic potential of Dp44mT-NPs against different malignant cells, with particularly promising results in highly-aggressive glioma tumor cells.