Development of magnetic nanoparticles for biomedical applications

The objective of this project is to design and synthesize magnetic nanoparticles with biocompatible coatings to which therapeutic molecules can be attached via a thermo-sensitive covalent bond. By applying an external alternating magnetic field (AMF), the superparamagnetic nanoparticles will generate heat, resulting in the breaking of the thermo-sensitive bonds. This will trigger the release of the attached organic moiety and therefore the concept can be employed for drug delivery applications.

Magnetic iron oxide nanoparticles (IONPs) represent one of the most promising innovations in the biomedical sector. Due to their small size and high surface-to-volume ratio they are endowed with a range of unique properties. In addition, IONPs are relatively easy and cheap to synthesize, non-toxic, biocompatible, chemically stable and can exhibit superparamagnetic behavior. Some of the recent developments of the IONPs in medicine include magnetic resonance imaging (MRI), hyperthermia treatment and drug delivery. When superparamagnetic nanoparticles are exposed to an external AMF, they generate magnetic energy that will dissipate in the form of heat, by Neel and/or Brownian relaxation. An AMF can thus be used to generate local heating for hyperthermia treatment, or to stimulate the release of therapeutic agents. Nanoparticles can be customized to combine therapeutic and diagnostic applications (theranostics) or multiple therapeutic functions (hyperthermia and drug delivery). In clinical trials it has been indicated that there is a synergistic effect of hyperthermia with chemotherapy, as this combination shows better efficacy than either hyperthermia or chemotherapy alone.

Targeted delivery can be achieved by attaching anticancer drugs to IONPs and injecting them intravenously. Nanoparticles accumulate passively in tumour tissue due to the ‘enhanced permeability and retention’ (EPR) effect. Besides this ‘passive’ targeting of the EPR effect, other ‘active’ targeting systems can be employed to improve the accumulation of IONPs in the target locations. Magnetic targeting is possible with IONPs because of their magnetic properties, by using an external magnetic field near the target to magnetically attract the nanoparticles to this location. Another possibility is to functionalize the nanoparticles with targeting agents or anti-bodies.

The drugs will be released by applying an AMF. However, it is challenging to monitor drug release by using standard analytical techniques. Therefore, optical probes such as luminescent lanthanide complexes and fluorescent dyes will be used in the first step to monitor the breaking of the thermo-sensitive bonds by AMF, and to demonstrate a proof-of-concept. This will also allow us to quantify the release mechanism for each thermo-sensitive bond. Once a suitable thermo-sensitive linkage has been identified and optimized, the therapeutical agents will be attached to NP by using the same linkage. Examples of drug molecules that we will attach are doxorubicin for cancer treatment or ibuprofen for treatment of inflammation, however this strategy can be used to attach many other therapeutic molecules. The toxicity and ability of these IONPs to specifically target cancer cells will be tested by performing cell studies.