Abstract

Exploiting and combining different properties of nanomaterials is considered a potential route for next generation cancer therapies. Magnetic nanowires (NWs) have shown good biocompatibility and a high level of cellular internalization. We induced cancer cell death by combining the chemotherapeutic effect of doxorubicin (DOX)-functionalized iron NWs with the mechanical disturbance under a low frequency alternating magnetic field. (3-aminopropyl)triethoxysilane (APTES) and bovine serum albumin (BSA) were separately used for coating NWs allowing further functionalization with DOX. Internalization was assessed for both formulations by confocal reflection microscopy and inductively coupled plasma-mass spectrometry. From confocal analysis, BSA formulations demonstrated higher internalization and less agglomeration. The functionalized NWs generated a comparable cytotoxic effect in breast cancer cells in a DOX concentration-dependent manner, (~60% at the highest concentration tested) that was significantly different from the effect produced by free DOX and non-functionalized NWs formulations. A synergistic cytotoxic effect is obtained when a magnetic field (1 mT, 10 Hz) is applied to cells treated with DOX-functionalized BSA or APTES-coated NWs, (~70% at the highest concentration). In summary, a bimodal method for cancer cell destruction was developed by the conjugation of the magneto-mechanical properties of iron NWs with the effect of DOX producing better results than the individual effects.

Highlights

  • Exploiting and combining different properties of nanomaterials is considered a potential route for generation cancer therapies

  • It has been reported that magnetic nanowires (NWs) offer potential advantages over magnetic nanoparticles (MNPs) because of their larger surface area to volume ratio and higher magnetic moments originated from their strong shape anisotropy[23,24]

  • We introduce a new bimodal strategy for cancer cell death induction by combining the chemotherapeutic effect of doxorubicin (DOX)-functionalized Fe NWs with the mechanical disturbance exerted by them when a low frequency alternating magnetic field (AMF) is applied

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Summary

Results and Discussion

Based on these results, BSA-NWs and APTES-NWs were selected for further functionalization with DOX to evaluate their potential on cancer cell death induction by combining the chemotherapeutic effect with the magneto-mechanical one. These results confirm the high degree of biocompatibility of Fe NWs formulations and the possibility to kill cancer cells by magneto-mechanical stimulation at the field parameters tested This mechanical effect is generated by the contribution of both internalized and membrane embedded NWs. It can be suggested that BSA is a more efficient coating agent with respect to killing of cancer cells by this method. This is relevant from a safety point of view, but it reduces the power consumption by several orders of magnitude, making it very efficient in terms of costs and technical implementation

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