Multifunctional dendrimer-based magnetite nanocarrier for pH-responsive drug delivery and MRI hyperthermia in breast cancer theranostics

Introduction: Breast cancer remains a major global health challenge, motivating the development of multifunctional nanoplatforms that unify diagnosis and therapy. This study presents a novel dendrimer-functionalized magnetite nanocarrier (MAGSiAG₁) and its ibuprofen-loaded derivative (IBU@MAGSiAG₁) designed for synergistic chemotherapy, magnetic hyperthermia, and MRI-guided theranostics.

Methods: Magnetite nanoparticles are synthesized and sequentially coated with SiO₂, APTES, cyanuric chloride, and poly(amidoamine) (PAMAM) G₁ dendrimer. Ibuprofen was loaded through sonication-assisted adsorption. Structural and physicochemical characterization was performed using different spectroscopic and imaging- and potential-based techniques, like FTIR, XRD, TGA, DLS, zeta potential, VSM, and SEM/TEM. pH-responsive drug release was evaluated across physiological and tumor-mimicking conditions. T2 relaxation and hence r2 relaxivity were quantified in MRI phantoms, and hyperthermia treatment was assessed under alternating magnetic field conditions (200 kHz, 100–150 Oe). In vitro cytotoxicity and live/dead imaging were conducted on MCF-7 breast cancer and EA. hy926 endothelial cells.

Results: IBU@MAGSiAG₁ featured stable spherical nanocarriers (~70 nm, −39 mV) with high ibuprofen loading (>90%). Drug release was accelerated at acidic pH (5.0–6.5) mimicking a cancer microenvironment, while it was suppressed at physiological pH 7.4. The nanocarriers retained superparamagnetic (35–40 emu/g) features and achieved therapeutic hyperthermia temperatures (~45 °C) at 150 Oe. High relaxivity (358.9 ± 5 mM⁻¹ s⁻¹ for MAGSiAG₁; 335.0 ± 49.8 mM⁻¹ s⁻¹ for IBU@MAGSiAG₁) confirmed strong MRI contrast enhancement. MCF-7 viability decreased to ~60% at 400 µg/mL, while EA.hy926 cells remained highly viable at ≤300 µg/mL, indicating selective therapeutic action.

Conclusions: This multifunctional dendrimer nanocarrier integrated MRI contrast enhancement, magnetic hyperthermia, and pH-triggered ibuprofen release into a single platform, enabling targeted ablation of breast cancer cells with acceptable biocompatibility. These results highlight its strong potential for personalized and image-guided cancer theranostics.