Theranostic Iron Oxide Nanoparticles for Controlled Oxaliplatin Release Under Simulated Circulation and Cytotoxicity Evaluation in Colorectal Cancer Cell Lines

Oxaliplatin (OXA) is a chemotherapeutic agent that suffers from poor pharmacokinetics and off-target toxicity. To enable controlled OXA release, we engineered a multi-functional iron oxide nanoparticle (IONPs) drug delivery system, based on pH-responsive mesoporous Fe3O4 (Fe3O4@MSN-NH2) nanoparticles (NPs), conjugated with folic acid (FA) for receptor-mediated targeting and guided by a magnetic robot platform (MRP) under simulated physiologically relevant dynamic circulation/flow system. For FA-conjugated NPs (Fe3O4@MSN-NH2/FA), ~29.73% OXA loading was achieved compared to ~10.3% in controls (Fe3O4@MSN-NH2/OXA), quantified by ICP-OES. Under dynamic circulation flow over 48 h, MRP enhanced pH-responsive OXA release (quantified by HPLC-UV), reaching ~92% and 88% (Fe3O4@MSN-NH2/OXA and Fe3O4@MSN-NH2/FA, respectively) at pH 5, versus 47% and 40% (Fe3O4@MSN-NH2/OXA and Fe3O4@MSN-NH2/FA, respectively) without MRP, demonstrating precise control in acidic tumor-mimicking conditions. MRI relaxometry exhibited strong T2-weighted contrast (T2 = 0.015 s at 50 μg/mL for Fe3O4@MSN-NH2/FA/OXA), confirming theranostic potential. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) studies revealed variable Folate receptor alpha (FOLR1) expression among colorectal cancer cell lines (Caco2, SW620, SW48, and T84), with Caco2 demonstrating high levels. MTT assays indicated selective targeting of FOLR1-positive cells by FA-functionalized NPs (Fe3O4@MSN-NH2/FA). This multi-functional drug delivery system integrates targeted delivery, MRP release, and real-time imaging, offering a promising technique for precision oncology.