Abstract
The folate analogue pemetrexed (PEM) is an approved therapeutic for non-small cell lung cancer and malignant pleural mesothelioma with the potential for broader application in combination therapies. Here, we report the development of a nanoformulation of PEM and its efficacy against the CT26 murine colorectal cancer cell line in vitro and in vivo. Utilizing layer-by-layer deposition, we integrate PEM, along with folic acid (FA), onto a fluorescent polystyrene nanoparticle (NP) substrate. The final nanoformulation (PEM/FA-NP) has a size of ∼40 nm and a zeta potential of approximately −20 mV. Cell uptake studies indicated increased uptake in vitro for the PEM/FA-NP compared to the uncoated NP, likely due to the presence of PEM and FA. Viability studies were performed to determine the potency of the PEM/FA-NP formulation against CT26 cells. Syngeneic CT26 tumors in BALB/c mice showed reduced growth when treated once daily (2.1 mg/kg PEM) for 3 days with PEM/FA-NP versus the vehicle (uncoated) control, with no observable signs of systemic toxicity associated with the nanoformulation. Although the current study size is limited (n = 4 animals for each group), the overall performance and biocompatibility of the PEM/FA-NP observed suggest that further optimization and larger-scale studies may be warranted for this novel formulation.
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