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Precision medicine with minimal side effects remains the goal of cancer therapy. Iron oxide nanoparticles are non-toxic, successful carriers of substances, targeting tissues and delivering high payloads of conjugated agents. Interfering RNA (siRNA) disrupts protein expression, an effective treatment e.g. for hereditary amyloidosis. This study tested transferrin-conjugated dopamine-coated iron oxide nanoparticle (TF-dpFe3O4) delivery of siRNA to cells overexpressing transferrin receptor (TFR). Method Cells were cultured in FBS-DMEM/F12. Fe3O4 nanoparticles were prepared by co-precipitation, dopamine coated +/- transferrin conjugation. LDH/MTT assays assessed cell viability responses to [TF-dpFe3O4] or [dpFe3O4]. Protein expression was examined by PAGE, densitometry and immunofluorescence. Targeting efficacy was determined by MEK2 gene silencing using siRNA-conjugated TF-dpFe3O4 or dpFe3O4. Result T-47D cells expressed high levels of TFR and MEK2. No significant effect on cell viability was observed with ≤2.5mg/mL TF-dpFe3O4 or dpFe3O4. By conventional transfection, 10nM siRNA lowered MEK2 expression levels to 25% (48hr); levels rebounded to 50% by 72hr. 10nM siRNA-conjugated TF-dpFe3O4 (2.5mg/mL) reduced MEK2 expression by 50% (72hr) without rebound; expression of a-tubulin (control) was unaffected. In contrast, as MEK2 levels decreased, TFR levels increased 2.2-fold (72hrs). Conclusion TF-dpFe3O4 nanoparticles are safe/efficient vehicles for delivering siRNA to cancer cells over-expressing TFR. Over 72hrs, protein expression of MEK2 reduced by 50%, a target superior to conventional methods. Notably: as the MAPK pathway was inhibited, increases in TFR levels were observed, suggesting adaptations to damage or stress. Take-home message TF-dpFe3O4 nanoparticles are a safe and efficient vehicle for delivering siRNA to cancer cells over-expressing TFR, allowing for successful targeting and inhibition of MAPK pathway proteins, such as MEK2, that drive tumour growth.

O22: CONJUGATED IRON NANOPARTICLES AS THERAPEUTIC CARRIERS FOR SPECIFIC TARGETING OF CANCER CELLS