Cancer remains a leading global health challenge, causing nearly 10 million deaths annually. We report a multifunctional magnetite-based dendrimer nanocarrier (MAGSiAG1) and its ibuprofen-loaded form (IBU@MAGSiAG1) for synergistic anti-cancer, anti-inflammatory, hyperthermia, and diagnostic applications. FTIR, XRD, TGA, DLS, and zeta potential analyses confirm successful sequential functionalization, dendrimer formation, and ibuprofen loading, resulting in spherical nanocarriers with an average hydrodynamic size of 70 nm and near-neutral surface charge (−39 mV) suitable for tumor penetration and systemic stability. VSM measurements reveal superparamagnetic behavior with saturation magnetization decreasing from 75 emu/g to 35–40 emu/g, ensuring strong magnetic responsiveness while maintaining colloidal stability. Under an alternating magnetic field (150 Oe), IBU@MAGSiAG1 achieves therapeutic temperatures (∼45 °C) via Néel and Brownian relaxation. In vitro relaxivity measurements showcase high T2 relaxivity coefficient (r2 = 358.88 ± 5 mM−1 s−1 for MAGSiAG1, 335 ± 49.8 mM−1 s−1 for IBU@MAGSiAG1), empowering effective MRI contrast. Drug loading efficiency exceeds 90%, with pH-responsive release profile that demonstrates accelerated ibuprofen release in acidic conditions (tumor-mimicking pH 5.0–6.5) and slower release at physiological pH (∼7.4). Cytotoxicity studies on MCF-7 human cancer cells reveal good viability (85–90%) at 250–400 μg/mL of drug concentration range, while higher concentrations (∼400 μg/mL) reduce viability to ∼60%, indicating therapeutic potential. Good biocompatibility of the developed nanocarriers is attained using with EA.hy926 endothelial cells, ensuring safe systemic delivery. Overall, IBU@MAGSiAG1 showcases high multifunctionality by integrating hyperthermia, controlled drug release, and MRI contrast into a single platform, paving the way for novel therapeutic targeted treatments in cancers that might advance personalized medicine approaches.

Multifunctional dendrimer nanocarrier loaded with ibuprofen for synergistic personalized theranostics and targeted ablation in breast cancer

Dabagh, Shadab;Adinolfi, Barbara;Giannetti, Ambra;Chiavaioli, Francesco
2025

Abstract

Cancer remains a leading global health challenge, causing nearly 10 million deaths annually. We report a multifunctional magnetite-based dendrimer nanocarrier (MAGSiAG1) and its ibuprofen-loaded form (IBU@MAGSiAG1) for synergistic anti-cancer, anti-inflammatory, hyperthermia, and diagnostic applications. FTIR, XRD, TGA, DLS, and zeta potential analyses confirm successful sequential functionalization, dendrimer formation, and ibuprofen loading, resulting in spherical nanocarriers with an average hydrodynamic size of 70 nm and near-neutral surface charge (−39 mV) suitable for tumor penetration and systemic stability. VSM measurements reveal superparamagnetic behavior with saturation magnetization decreasing from 75 emu/g to 35–40 emu/g, ensuring strong magnetic responsiveness while maintaining colloidal stability. Under an alternating magnetic field (150 Oe), IBU@MAGSiAG1 achieves therapeutic temperatures (∼45 °C) via Néel and Brownian relaxation. In vitro relaxivity measurements showcase high T2 relaxivity coefficient (r2 = 358.88 ± 5 mM−1 s−1 for MAGSiAG1, 335 ± 49.8 mM−1 s−1 for IBU@MAGSiAG1), empowering effective MRI contrast. Drug loading efficiency exceeds 90%, with pH-responsive release profile that demonstrates accelerated ibuprofen release in acidic conditions (tumor-mimicking pH 5.0–6.5) and slower release at physiological pH (∼7.4). Cytotoxicity studies on MCF-7 human cancer cells reveal good viability (85–90%) at 250–400 μg/mL of drug concentration range, while higher concentrations (∼400 μg/mL) reduce viability to ∼60%, indicating therapeutic potential. Good biocompatibility of the developed nanocarriers is attained using with EA.hy926 endothelial cells, ensuring safe systemic delivery. Overall, IBU@MAGSiAG1 showcases high multifunctionality by integrating hyperthermia, controlled drug release, and MRI contrast into a single platform, paving the way for novel therapeutic targeted treatments in cancers that might advance personalized medicine approaches.
2025
Istituto di Fisica Applicata - IFAC
Breast cancer
Hyperthermia
Ibuprofen
MRI contrast agent
Multifunctional dendrimer nanocarrier
Theranostics
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.14243/601181
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