Background: Cancer therapeutics development has been a challenge in medical and scientific areas due to their toxicity, limited biocompatibility, and unfortunate side effects. However, despite advances in early detection and the study of novel treatments, the mortality rate for breast cancer remains high, making it a significant global health concern. Objectives: In this study, poly(methyl methacrylate) (PMMA) nanoparticles functionalized with acrylic acid (AA), fumaramide (FA), and curcumin (CUR) as chelating and inhibitor agents were synthesized by emulsion polymerization techniques. Methods and Results: Comprehensive physiochemical characterization studies based on gravimetry, dynamic light scattering (DLS), electrophoresis, Fourier transform infrared (FT-IR), ultraviolet–visible (UV–Vis) and photoluminescence (PL) spectroscopy, X-ray diffraction (XRD), and scanning electron microscopy (SEM) revealed a pH dependence of nanoparticles that exhibit structural changes upon interaction with calcium (Ca²⁺) and magnesium (Mg²⁺) ions. Calorimetric thermodynamic properties measured by isothermal titration calorimetry (ITC) confirmed chelating coordination and positive cooperativity between the nanoparticles and metal ions. In vitro studies showed the low cytotoxicity of nanoparticles by fibroblast proliferation, and their chelation process was observed by fluorescence microscopy, with the loss of interaction between cells. Conclusions: These results suggest that the functionalized nanoparticles have potential in drug delivery systems (DDS) for targeted breast cancer therapies, providing a promising polymer material for more efficient and less toxic treatments.

Cancer therapeutics development has been a challenge in medical and scientific areas by their toxicity, biocompatibility and unfortunate side effects on the human body. However, despite advances in early detection and the study of novel treatments, the mortality rate for breast cancer remains high, making it a significant global health concern. Thus, there is still a need for more effective and targeted therapies, where nanotechnology emerges as a promising solution in this field. For this reason, four series of core–shell for breast cancer remains poly(methyl methacrylate, MMA) nanoparticles functionalized with acrylic acid (AA), fumaramide (FA) and curcumin (CUR) as chelating agents were synthesized by emulsion polymerization techniques. Comprehensive physiochemical characterization studies based on gravimetry, dynamic light scattering (DLS), electrophoresis, Fourier transform infrared (FT-IR), ultraviolet-visible (UV-Vis) and photoluminescence (PL) spectroscopy, X-ray diffraction (XRD) and scanning electron microscopy (SEM) were made to analyze their pH-dependence. The calorimetric thermodynamic properties of interaction between the particles and calcium chloride (CaCl2) or magnesium chloride (MgCl2) solutions were evaluated by isothermal titration calorimetry (ITC). Among the most relevant results were that nanoparticles showed a strong pH-dependence by underwent structural changes when they interacted with calcium (Ca2+) and magnesium (Mg2+) ions. Furthermore, the interaction parameters such as intermolecular forces, binding constant (Kb), interaction enthalpies (H), and Gibbs free energy (G) confirmed a strong coordination bond between the functional groups and the metal ions. According to obtained results, nanoparticles could have the ability to chelate ions available in the medium, suggesting their potential use in improving drug delivery systems (DDS) for breast cancer therapies.