Biomimetic magnetic nanoparticles for its use in biotechnological applications

Researchers of the University of Granada have carried out a study of functional improvement of the nanoparticles of chemical synthesis throughout the introduction of a recombinant protein in the aqueous solution where magnetite is formed. Then, a biomimetic magnetic nanoparticles are generated which solve requirements such as biocompatibility, surface charge of the nanoparticles and their size, which determine their magnetic properties. These properties make them show great advantages compared to other already existing in the market for biomedical use, as well as solving the existing bottleneck in production for ther commercial use. In that case, researchers have used a recombinant protein MamC mixed with other proteins of the magnetosome in magnetotactic bacteria which, in these bacteria, have a regulatory function in the process of in vivo  magnetite formation.

The production of magnetic nanoparticles generates millions of dollars every year in the United States. They are used in different clinical fields, such as polymorphisms detection, cell separation, purification and isolation of DNA, resonance imaging, early diagnosis and as nanotransporters for chemotherapy, immunotherapy and directed gene therapy.

The advantage of the magnetic nanoparticles againsts other nanoparticles is that they can be manipulated through an external magnetic field. The size of the nanoparticles is the limitating parameter because it determines their magnetic properties and the response to the external magnetic field. In order to increase the effectiveness of the biomedical treatments in different diseases such as, for example, cancer, is necessary that the nanoparticles have a hyperthermical response and be able to increase the medium tempresature where they are up to a value of 42-43 ºC in response either to radiation or an altern magnetic field.

The comercial nanoparticles produced through chemical synthesis have a very low size (<30nm), and show a superparamagnetic behavior with relatively low coercitivity values against external fields. On the contrary, the magnetosomes of magnetotactic bacteria would be the ideal magnetic nanoparticles, but they are not industrially viables because their production cannot be scaled.

Researchers have studied their response against hyperthermia with the necessary parameters of temperature and magnetic nanoparticles size, reaching the 43ºC on their rotation against a magnetic field, and comprised in the interval 30-120nm, meaning that they show a single magnetic domain and not a superparamagnetic characterization.

ADVANTAGES

• The biomimetic nanoparticles developed on this invention have a size of ~40 nm, which make them being singular magnetic domains, paramagnetics at room temperature in abscense of a field and, on the other hand, show a great coercivity in the presence of an external magnetic field, higher than the smallest commercial nanoparticles. That makes that these particles, in the absence of a magnetic field, will remain stable and not aggregate, while, when an external magnetic field is introduced in order to guide them to the target site, these nanoparticles show hyperthermia.
• When compared to magnetosomes, the biomimetic magnetic nanoparticles have the advantage that their production can be scaled.
• The biomimetic nanoparticles  of the present invention are charged at physiological pH and discharged at tumor pH, thanks to their surface proteins, Unlike tha commercial nanoparticles, which are discharged at physiological pH and charged at tumor pH. This facilitates their functionalization with the chosen molecule and its later liberation in response to a pH change that occurs in a natural manner when passing from bloodstream to the tumor
• The nanoparticles can be encapsulated forming magnetoliposomes, in a way that the transported molecule can be protected from degradation or if it is toxic. The magnetoliposomes can be functionalized in orde to recognize a marker and then make a selective transport.
• Both the biomimetic nanoparticles functionalized or not, and/or encapsulated in liposomes show a hypothermic response.
• They can be used for the next techniques:
  • Functionalized transporters
  • Contrast agents for imaging or magnetic resonance
  • Bone marrow purge techniques
  • DNA isolation

Particle separation

Current development status

Experimental technologies

Applications

cancer, immunotherapy, oncotherapy, directed therapies, imaging