BioMedical applications

Magnetically Targeted Drug Delivery is a Pill Version 2.0. Actually, it is something far greater than that. When you swallow a pill, the allied drug molecules are subjected to numerous dangers before they reach the target of their journey, whether it be tissue in an inflamed state or cancer cells, they are attacked many times and in many different fashions – seized by proteins, cracked and transformed by enzymes, excreted via various routes and as a result the actual efficiency of the drug can drop dramatically by as much as up to 10%.  Imagine the perfect situation where this problem is mitigated, where we steer and protect the drug throughout its entire journey within the body of a patient. In the not too distant future this could become reality. As the drug itself is susceptible to multiple attacks it must be loaded and anchored onto (by functionalization) or hidden inside (by encapsulation) the vehicle and if the vehicle is additionally equipped with a tiny magnet and steered by a magnetic field then the whole system becomes magnetically targeted and this is what is known as Magnetically Targeted Drug Delivery. The ideal candidate for such a carrier due to its unique combination of nano-needle aerodynamics, physicochemical and biological properties is Multi-wall Carbon Nanotube (MWCNT).

 

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However there are some fundamental questions that emerge: how safe is the carrier itself? How effectively does it cross the biological barriers – cell and nuclear membranes, especially if the drug must be delivered in close proximity to DNA. We have answered these questions by performing cytotoxicological in vitro assays (in collaboration with Dr. Karin Müller and Dr. Jeremy Skepper from the Department of Physiology, Development and Neuroscience, University of Cambridge, UK) which revealed that MWCNTs are non-toxic and can be safely eliminated (excreted) from the body and in particular after oxidative pre-treatment MWNCTs become dispersible in aqueous media; Alexander Star and colleagues (University of Pittsburgh, USA) have also been studying the possibility of enzymatic digestion of MWCNTs.  In summary, the nanotube carriers caneffectively cross cellular and nuclear membrane and are therefore capable of delivering a drug inside a cell.

Key questions are how to provide the carrier with a magnet and how to efficiently anchor, safely deliver and quantitatively unload the drug inside the target. We have investigated a variety of procedures for anchoring the drug to the outer surface of MWCNT carriers, e.g. via oxidative pre-treatment or cycloaddition reactions. We have also designed strength of the linkage by applying physical or chemical interactions between drug and carrier. We have achieved anchoring with anti-cancer drugs, i.e. 5-fluorouracil and purpurin derivatives to MWCNTs, and the drug-loads constituted as much as 30% per weight of the system (system = carrier + drug). In turn, the magnet is conveniently formed in the stage of synthesis of MWCNTs – since nanotubes require a catalyst for their growth, iron nanoparticles serve both as the catalyst and then as a ferromagnetic core in the nanotube.

We have designed and tested MWCNT-drug hybrids in preliminary in vitro assays and these biologically active hybrids were able to combat cancer cells (Human Melanoma Me-45 and epithelial colorectal cancer CaCo-2 cell lines) which is of significant importance for our future work focusing on using carbon nanostructures as Magnetically Targeted Drug Delivery systems. Whilst there are still significant challenges ahead, such as how to achieve aggregation of magnetic nanoparticules via magnetisation prior to in vivo trials, it is not such a leap of the imagination to envisage a time when efficient cell-penetrating, harmless and excretable nanotube vehicles bearing chemotherapeutics will transform the treatment of a wide range of cancers.