Magnetic core-shell nanowires as MRI contrast agents for cell tracking.

BACKGROUND: Identifying the precise location of cells and their migration dynamics is of utmost importance for achieving the therapeutic potential of cells after implantation into a host. Magnetic resonance imaging is a suitable, non-invasive technique for cell monitoring when used in combination with contrast agents. RESULTS: This work shows that nanowires with an iron core and an iron oxide shell are excellent materials for this application, due to their customizable magnetic properties and biocompatibility. The longitudinal and transverse magnetic relaxivities of the core-shell nanowires were evaluated at 1.5 T, revealing a high performance as T2 contrast agents. Different levels of oxidation and various surface coatings were tested at 7 T. Their effects on the T2 contrast were reflected in the tailored transverse relaxivities. Finally, the detection of nanowire-labeled breast cancer cells was demonstrated in T2-weighted images of cells implanted in both, in vitro in tissue-mimicking phantoms and in vivo in mouse brain. Labeling the cells with a nanowire concentration of 0.8 µg of Fe/mL allowed the detection of 25 cells/µL in vitro, diminishing the possibility of side effects. This performance enabled an efficient labelling for high-resolution cell detection after in vivo implantation (~ 10 nanowire-labeled cells) over a minimum of 40 days. CONCLUSIONS: Iron-iron oxide core-shell nanowires enabled the efficient and longitudinal cellular detection through magnetic resonance imaging acting as T2 contrast agents. Combined with the possibility of magnetic guidance as well as triggering of cellular responses, for instance by the recently discovered strong photothermal response, opens the door to new horizons in cell therapy and make iron-iron oxide core-shell nanowires a promising theranostic platform.

Iron-Based Core-Shell Nanowires for Combinatorial Drug Delivery and Photothermal and Magnetic Therapy.

Combining different therapies into a single nanomaterial platform is a promising approach for achieving more efficient, less invasive, and personalized treatments. Here, we report on the development of such a platform by utilizing nanowires with an iron core and iron oxide shell as drug carriers and exploiting their optical and magnetic properties. The iron core has a large magnetization, which provides the foundation for low-power magnetic manipulation and magnetomechanical treatment. The iron oxide shell enables functionalization with doxorubicin through a pH-sensitive linker, providing selective intracellular drug delivery. Combined, the core-shell nanostructure features an enhanced light-matter interaction in the near-infrared region, resulting in a high photothermal conversion efficiency of >80% for effective photothermal treatment. Applied to cancer cells, the collective effect of the three modalities results in an extremely efficient treatment with nearly complete cell death (∼90%). In combination with the possibility of guidance and detection, this platform provides powerful tools for the development of advanced treatments.

Functionalized magnetic nanowires for chemical and magneto-mechanical induction of cancer cell death.

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.