Clinical Translation of Inorganic Nanoparticles and Engineered Living Materials for Cancer Therapy.

A wide range of particle-based nano- to microsystems is currently under investigation for potential use in personalized nanomedicine. However, only a small fraction of these innovations is likely to make it to clinical use. In this concept article, we start by discussing the potential applications of inorganic nanoparticles in cancer treatment and diagnosis, and shed light on the challenges they must overcome to become clinically available. In the second part, we delve into engineered living materials, which have begun to revolutionize the way medical interventions could be performed. Finally, we share our insights and opinions to explain why, despite significant advancements in research on these technologies, their translation to clinical practice remains limited.

Intracellular transformation and disposal mechanisms of magnetosomes in macrophages and cancer cells.

Magnetosomes are magnetite nanoparticles biosynthesized by magnetotactic bacteria. Given their potential clinical applications for the diagnosis and treatment of cancer, it is essential to understand what becomes of them once they are within the body. With this aim, here we have followed the intracellular long-term fate of magnetosomes in two cell types: cancer cells (A549 cell line), because they are the actual target for the therapeutic activity of the magnetosomes, and macrophages (RAW 264.7 cell line), because of their role at capturing foreign agents. It is shown that cells dispose of magnetosomes using three mechanisms: splitting them into daughter cells, excreting them to the surrounding environment, and degrading them yielding less or non-magnetic iron products. A deeper insight into the degradation mechanisms by means of time-resolved X-ray absorption near-edge structure (XANES) spectroscopy has allowed us to follow the intracellular biotransformation of magnetosomes by identifying and quantifying the iron species occurring during the process. In both cell types there is a first oxidation of magnetite to maghemite and then, earlier in macrophages than in cancer cells, ferrihydrite starts to appear. Given that ferrihydrite is the iron mineral phase stored in the cores of ferritin proteins, this suggests that cells use the iron released from the degradation of magnetosomes to load ferritin. Comparison of both cellular types evidences that macrophages are more efficient at disposing of magnetosomes than cancer cells, attributed to their role in degrading external debris and in iron homeostasis.

Magnetic Anisotropy of Individual Nanomagnets Embedded in Biological Systems Determined by Axi-asymmetric X-ray Transmission Microscopy.

Over the past few years, the use of nanomagnets in biomedical applications has increased. Among others, magnetic nanostructures can be used as diagnostic and therapeutic agents in cardiovascular diseases, to locally destroy cancer cells, to deliver drugs at specific positions, and to guide (and track) stem cells to damaged body locations in regenerative medicine and tissue engineering. All these applications rely on the magnetic properties of the nanomagnets which are mostly determined by their magnetic anisotropy. Despite its importance, the magnetic anisotropy of the individual magnetic nanostructures is unknown. Currently available magnetic sensitive microscopic methods are either limited in spatial resolution or in magnetic field strength or, more relevant, do not allow one to measure magnetic signals of nanomagnets embedded in biological systems. Hence, the use of nanomagnets in biomedical applications must rely on mean values obtained after averaging samples containing thousands of dissimilar entities. Here we present a hybrid experimental/theoretical method capable of working out the magnetic anisotropy constant and the magnetic easy axis of individual magnetic nanostructures embedded in biological systems. The method combines scanning transmission X-ray microscopy using an axi-asymmetric magnetic field with theoretical simulations based on the Stoner-Wohlfarth model. The validity of the method is demonstrated by determining the magnetic anisotropy constant and magnetic easy axis direction of 15 intracellular magnetite nanoparticles (50 nm in size) biosynthesized inside a magnetotactic bacterium.

Unlocking the Potential of Magnetotactic Bacteria as Magnetic Hyperthermia Agents.

Magnetotactic bacteria are aquatic microorganisms that internally biomineralize chains of magnetic nanoparticles (called magnetosomes) and use them as a compass. Here it is shown that magnetotactic bacteria of the strain Magnetospirillum gryphiswaldense present high potential as magnetic hyperthermia agents for cancer treatment. Their heating efficiency or specific absorption rate is determined using both calorimetric and AC magnetometry methods at different magnetic field amplitudes and frequencies. In addition, the effect of the alignment of the bacteria in the direction of the field during the hyperthermia experiments is also investigated. The experimental results demonstrate that the biological structure of the magnetosome chain of magnetotactic bacteria is perfect to enhance the hyperthermia efficiency. Furthermore, fluorescence and electron microscopy images show that these bacteria can be internalized by human lung carcinoma cells A549, and cytotoxicity studies reveal that they do not affect the viability or growth of the cancer cells. A preliminary in vitro hyperthermia study, working on clinical conditions, reveals that cancer cell proliferation is strongly affected by the hyperthermia treatment, making these bacteria promising candidates for biomedical applications.