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

Ylenia Jabalera,Maria Prat,Guillermo R Iglesias,Alberto Sola-Leyva,Concepcion Jimenez-Lopez,Maria P Carrasco-Jiménez,Ana Peigneux,Francesca Oltolina

doi:10.3390/polym12081832

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.

Highlights

The need to combine therapies to increase efficiency is gaining relevance, especially in the context of cancer [1,2]
Results from the present study show that the nanoformulation here proposed, integrated by a combination of two different types of magnetic nanoparticles, one inorganic with an average size of ~15 nm, and the other biomimetic
The inorganic nanoparticles show good potential as magnetic hyperthermia agents, while the biomimetic nanoparticles are better suitable as nanocarrier, being able to be functionalized with a drug and a targeting probe by electrostatic interaction, being the release of the drug pH dependent

Summary

Introduction

The need to combine therapies to increase efficiency is gaining relevance, especially in the context of cancer [1,2]. In the context of cancer, this is especially relevant because all the most consolidated therapies (surgery, radiotherapy, chemotherapy, and photodynamic therapy) are not fully effective, especially chemo- and radiotherapy, which provoke severe side effects due to their lack of specificity [3]. For this reason, alternative strategies are becoming attractive, and among them, magnetic hyperthermia (MH). MH is the result of the application of an alternating magnetic field (AMF) to hyperthermia agents (such as iron oxide or gold nanoparticles) that, as a result, generate local heat at the tumor site. Such a local temperature increase induces the apoptosis or necrosis of tumor cells, which are more sensitive than normal healthy cells to the increased temperature of about 43 ◦ C [5,6]

Methods

Results

Conclusion