Engineering triphenyl phosphonium conjugated iron oxide nanoparticles for Oxaliplatin loading: Application in cancer treatment

Cancer remains one of the most pervasive and lethal diseases globally, with conventional chemotherapy often failing to effectively eradicate tumors or prevent their progression (e.g., breast, ovarian, and colon cancers). Iron oxide nanoparticles (Fe3O4 NPs) have emerged as promising candidates for drug delivery in cancer treatment due to their excellent biocompatibility, versatile surface chemistry, tunable magnetic properties, and potential for multi-modal applications on a single platform. In this study, the unique contribution lies in the functionalisation of Fe3O4 NPs with (3-carboxypropyl) triphenylphosphonium bromide (TPP) and their subsequent loading with the chemotherapeutic agent oxaliplatin (OXA). TPP functionalization can enable mitochondrial targeting, providing a novel strategy to enhance drug delivery efficacy. The Fe3O4 NPs were synthesised via a co-precipitation reaction at elevated temperature (80 °C) and high pH (11), followed by coating with tetraethyl orthosilicate (TEOS) and 3-aminopropyltriethoxysilane (3-APTES), and functionalisation with TPP. Analytical characterisation (XPS, ICP-OE) confirmed the successful TPP functionalisation and loading of OXA. Notably, the nanoparticles exhibited good stability across a range of temperatures (4 °C, 25 °C, 37 °C, and 43 °C) and retained their superparamagnetic properties, highlighting their suitability for biomedical applications. Cell toxicity analysis has shown that the IC50 values (i.e. the concertation at which 50 % of cell growth is inhibited) of corresponding OXA concentration delivered by the NPs is comparable with the pure OXA, suggesting an effective drug delivery to the cells using NPs. It should be noted that the TPP modification was aimed at enabling mitochondrial targeting and promoting immunogenic cell death, both of which will be further investigated in future in vitro/in vivo studies.