Magnetic nanomotors with integrated theranostic capabilities

(Nanowerk Spotlight) The role of artificial nanomotors integrated with therapeutic capabilities is a very promising field for clinical applications of medical nanotechnology. One example being developed by researchers is a ferromagnetic nanomotor that can be maneuvered in blood under rotating magnetic fields. In a previous Nanowerk Spotlight we have already reported on such magnetic nanovoyagers in human blood.
The system of ferrite coated nanomotors could have great potential in the field of cancer therapeutics where the temperature rise of the local cell environment leads to cell death in the case of cancer cells via cytotoxic effects.
Researchers at the Indian Institute of Science (IISc) in Bangalore now have demonstrated the integration of hyperthermia potential to nanomotors that can be remotely maneuvered. Reporting their findings in Nanoscale ("Single Coating of Zinc Ferrite Renders Magnetic Nanomotors Therapeutic and Stable against Agglomeration"), the team also tackled the problem of magnetic agglomeration associated with ferromagnetic nanomotors, which limits their biomedical application.
"Our work demonstrates the intelligent design of nanomotors with a single coating of ferrite, which act as a spacer layer as well as providing therapeutic potential by magnetic hyperthermia," Pooyath Lekshmy Venugopalan, a research associate at IISc Bangalore's Centre for Nano Science and Engineering, and first author of the paper, tells Nanowerk. "The two functionalities are inter-related since higher hyperthermia efficiency required a denser suspension, both of which were achieved in a single microwave-synthesized ferrite coating. This allows the scaling up of this system of magnetic nanomotors which is very essential for therapeutic applications."
Representative bright field microscopic images of HeLa cells with ferrite coated nanomotors  (a) before and (b) after hyperthermia run
Representative bright field microscopic images of HeLa cells with ferrite coated nanomotors (a) before and (b) after hyperthermia run following trypan blue staining. (Image: Indian Institute of Science, Bangalore) (click on image to enlarge)
The potential of magnetic hyperthermia using artificial nanomotors had not been explored so far, including their cytotoxic effects on cancer cells. The IISc team has been able to integrate this functionality to the nanomotors along with enhanced physical stability (against agglomeration) for over 6 months using a single microwave-synthesized ferrite coating, which acts as a steric layer.
These findings pave way for future therapeutic and diagnostic applications using these nanomotors, where their localized heating effect and long- term stability is very essential.
As the scientists demonstrated in their paper, incorporating a spacer layer around the helical nanomotor in a core-shell configuration can provide a promising route to achieve long term stability against agglomeration in a suspension of ferromagnetic nanomotors, similar to superparamagnetic systems.
"The addition of the ferrite layer improved the stability of the suspension by an order of magnitude while ensuring their propulsion efficiency was unchanged," explains Venugopalan. "The ferrite layer also provided additional therapeutic value in the form of magnetic hyperthermia potential. The ferrite thickness, here 150 nm, was a crucial part of the design which needed to be small enough such that the helical shape was retained, and large enough to provide significant hyperthermia potential, apart from acting as a spacer as mentioned before."
The ferrite layer allowed a higher concentration of ferromagnetic nanomotors, which resulted in stronger hyperthermia effect and consequent cytotoxicity on cancer cells.
"Although there has been prior demonstration of nanoparticles being used for magnetic hyperthermia, including those made of ferrites, as far as we know, this is the first demonstration of integration of hyperthermia potential to nanomotors that can be remotely maneuvered," Venugopalan points out.
Ferrite-coated nanomotors maneuvered in a dish containing adhered HeLa cells in culture media. (Video: Indian Institute of Science, Bangalore)
The main difference between the design reported by the IISc team and previous examples of magnetic nanomotors is in the use of the ferrite coating, incorporated as a steric layer around the ferromagnetic material (here, iron).
The ferrite coating on magnetic nanomotors promises new possibilities in the in vivo applicability of artificial nanomotors, especially with regard to integrating theranostic capabilities.
One could envision bringing the nanomotors in close proximity to a cancerous tissue, for diagnostic and simultaneous therapeutic applications. We are looking to engineer multifunctional intelligent nanomotor that can sense and detect bio environments, deliver drugs with in situ visualization, all functionalities incorporated on a single nanomotor.
"We are planning to further investigate the combined effects of hyperthermia with drug release from nanomotors as they would be more beneficial compared to individual effects," notes Venugopalan. "Along with biomedical applications, these nanomotors with their enhanced physical and chemical stabilities could be used to study collective phenomena in a dense suspension of nanomotors."
Having controlled motion in important biological environments automatically suggests a general platform towards diagnostic and therapeutic applications. It is possible to functionalize the nanomotors with appropriate bio-chemicals, which can be used to detect and treat diseases.
Functionalize nanomotors with various molecules also could be beneficial for imaging, sensing specific molecules of interest, drug molecules etc. The researchers are also looking at ways to improve the hyperthermia efficiency of these nanomotors by addition of dopants and modifying ferrite compositions.
Further research in this area will be directed towards in vivo experiments using ferrite coated nanomotors. Drug release in conjunction with magnetic hyperthermia is of great interest for local targeted therapy and further research would be directed along these lines which could have great implications for cancer therapeutics. However, for imaging these nanomotors in vivo would require the development of novel imaging techniques.
Michael Berger By – Michael is author of three books by the Royal Society of Chemistry:
Nano-Society: Pushing the Boundaries of Technology,
Nanotechnology: The Future is Tiny, and
Nanoengineering: The Skills and Tools Making Technology Invisible
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