A new generation of pH-responsive magnetic theranostic nanovectors (NV) has been developed to deliver doxorubicin (DOX) to triple negative breast cancer (TNBC) cells which overexpress epidermal growth factor receptor EGFR. DOX was loaded onto functionalized NV using a pH-sensitive DOX-Fe2+ complex (hereafter called NVscFv-DOX). NVscFv-DOX consists of superparamagnetic iron oxide nanoparticles (SPIONs), labelled with DylightTM 680 fluorophore, and coated with a layer of covalently bound polyethylene-glycol (PEG) which is partially functionalized with anti-EGFR scFvs (average ratio is ≈12 scFv per nanovector). The physico-chemical characteristics of the new nanovectors were suitable for IV injection: hydrodynamic diameter DH below 150 nm, polydispersity index below 0.3 and slightly negative surface charge (≈ -10 mV). Thanks to the functional grafted scFvs, the NVscFv-DOX were able to recognize the EGFR antigen efficiently. Using preformed DOX-Fe2+ complex which binds to the SPION surface in a pH-dependent manner, about 6.5% w/w (DOX/iron oxide) of the drug were loaded onto the NVscFv-DOX. The drug loading and release in its native form at acidic pH were characterized by surface-enhanced Raman scattering (SERS) spectroscopy. The dual fluorescent response of both DylightTM680 and that of DOX was confirmed, which is promising for theranostic use of the nanovectors. Finally, the in vitro toxicity of NVscFv-DOX on the EGFR-overexpressing TNBC cell line MDA-MB-468 was confirmed and compared to that of free DOX and NVscFv without DOX. Together, all these properties of the NVscFv-DOX are promising for their potential use as theranostic platform for TNBC treatment.
Lameli et al. (Sun,) studied this question.
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