O)] (CuL1), which has demonstrated anticancer activity, was encapsulated into Eudragit®-based nanoparticles to enhance its effects against TNBC cell lines (MDA-MB-231, 4 T1, and Hs 578 T). Two nanosystems were prepared by nanoprecipitation followed by ultrasonication, using Eudragit® E100/S100 (ES-CuL1) or Eudragit® E100/NE100D (ENE-CuL1). The physicochemical and morphologic properties were characterized by dynamic light scattering (DLS), transmission electron microscopy (TEM), fourier transformed infrared spectroscopy (FTIR), and small-angle X-ray scattering/wide-angle X-ray scattering (SAXS/WAXS). Both formulations showed encapsulation efficiencies of CuL1 above 90 % and in vitro controlled drug release over 72 h. Cytotoxicity and apoptosis were evaluated in 2D monolayers and 3D spheroids of TNBC. Notably, ES-CuL1 enhances the cytotoxic activity of CuL1, showing increased cytotoxicity across all 2D cell lines. Consistently, the encapsulated complex significantly reduced clonogenic survival from 0.5 µM onward and induced a higher proportion of late apoptotic cells in all tested lines. In 3D models, ES-CuL1 produced similar effects to the free drug in 4 T1 spheroids but elicited a stronger cytotoxic response in Hs 578 T spheroids, suggesting improved penetration and retention in tumor-like structures. The superior performance of ES-CuL1 supports its potential as effective nanocarrier for BC therapy and highlights the predictive value of 3D spheroids for nanodrug evaluation.
Boztepe et al. (Fri,) studied this question.