Biogenic Magnetic Nanoplatform for Dual Tumor Microenvironment-Responsive Aripiprazole Delivery in Breast Cancer

Breast cancer remains a major global health challenge, highlighting the need for targeted drug delivery systems with improved therapeutic efficacy and reduced systemic toxicity. In this study, a green-synthesized dual-responsive magnetic nanoplatform, Iron oxide@Tween 80-PEG-ARI-NPs, was developed for targeted breast cancer therapy. Iron oxide nanoparticles were synthesized using Nephelium lappaceum (Rambutan) peel extract as an eco-friendly reducing and stabilizing agent, followed by functionalization with Tween 80, polyethylene glycol (PEG), and aripiprazole (ARI) loading. Comprehensive characterization using FTIR, XRD, SEM-EDX, HR-TEM, DLS, TGA/DTA, and VSM confirmed successful surface modification, spherical morphology, preserved crystallinity, superparamagnetic behavior, and enhanced colloidal stability. In vitro drug release studies demonstrated minimal ARI leakage at physiological pH 7.4 and accelerated release under acidic pH 5.5 and oxidative conditions, reaching 70.40% ± 0.55% and 90.35% ± 5.15% cumulative release after 60 h, respectively. Release kinetics followed anomalous non-Fickian diffusion under acidic conditions and quasi-Fickian diffusion at physiological pH. The nanoparticles exhibited significant anti-inflammatory activity and potent cytotoxicity against MCF-7 breast cancer cells, with an IC₅₀ of 40.2 ± 2.15 µg/mL, inducing pronounced apoptotic morphological changes. These findings demonstrate the potential of Iron oxide@Tween 80-PEG-ARI-NPs as an effective dual-responsive magnetic nanocarrier for targeted breast cancer therapy with enhanced therapeutic potential.