Nanoformulation Design Including MamC-Mediated Biomimetic Nanoparticles Allows the Simultaneous Application of Targeted Drug Delivery and Magnetic Hyperthermia.

ABSTRACT

The design of novel nanomaterials that can be used as multifunctional platforms allowing the combination of therapies is gaining increased interest. Moreover, if this nanomaterial is intended for a targeted drug delivery, the use of several guidance methods to increase guidance efficiency is also crucial. Magnetic nanoparticles (MNPs) allow this combination of therapies and guidance strategies. In fact, MNPs can be used simultaneously as drug nanocarriers and magnetic hyperthermia agents and, moreover, they can be guided toward the target by an external magnetic field and by their functionalization with a specific probe. However, it is difficult to find a system based on MNPs that exhibits optimal conditions as a drug nanocarrier and as a magnetic hyperthermia agent. In this work, a novel nanoformulation is proposed to be used as a multifunctional platform that also allows dual complementary guidance. This nanoformulation is based on mixtures of inorganic magnetic nanoparticles (M) that have been shown to be optimal hyperthermia agents, and biomimetic magnetic nanoparticles (BM), that have been shown to be highly efficient drug nanocarriers. The presence of the magnetosome protein MamC at the surface of BM confers novel surface properties that allow for the efficient and stable functionalization of these nanoparticles without the need of further coating, with the release of the relevant molecule being pH-dependent, improved by magnetic hyperthermia. The BM are functionalized with Doxorubicin (DOXO) as a model drug and with an antibody that allows for dual guidance based on a magnetic field and on an antibody. The present study represents a proof of concept to optimize the nanoformulation composition in order to provide the best performance in terms of the magnetic hyperthermia agent and drug nanocarrier.