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.

Synergistic Photothermal-Chemotherapy Based on the Use of Biomimetic Magnetic Nanoparticles

“…The increase of temperature reached upon photothermia probably provided enough thermal energy to weaken the electrostatic bond that was keeping DOXO attached to BMNPs, thus accelerating the kinetics of DOXO release. These results are different than those occurring following magnetic hyperthermia with the same particles, where no DR increase was observed [40], but they are in accordance with that discussed above: the stronger effect of photothermia on BMNPs compared to that of magnetic hyperthermia.…”

“…The ability of the nanoassembly to perform as a drug nanocarrier was evaluated at pH 7.4 (physiological pH) and pH 5 (mimicking the environment in the endosomal/lysosomal compartment [43]), both with and without photothermia (Figure 3A, Table 1). During the first 30 min of the experiment, the DOXO release from the nanoassembly at physiological pH was very low, with release efficiency (DR) values that did not exceed 8% of the adsorbed drug, thus indicating the stability of the nanoformulation at physiological pH values, as it has been previously proven by other studies [32,40]. However, performing this experiment under sample irradiation, DR values increased up To evaluate sample homogeneity in terms of temperature increase, the temperature at three different positions within the samples was recorded.…”

Biomimetic Magnetite Nanoparticles as Targeted Drug Nanocarriers and Mediators of Hyperthermia in an Experimental Cancer Model

“…Although still not ideal, these BMNPs have improved colloidal stability compared to MNPs, even if they are larger (36 ± 12 nm) than the latter (<30 nm). After functionalization with DOXO, their size is only slightly increased (of about 4%) [39].…”

“…Although still not ideal, BMNPs have improved colloidal stability compared to MNPs, even if they are larger than the latter. Ways to improve colloidal stability that are presently investigated by our research group are embedding the BMNPs in liposomes [34], covering the BMNPs with protein corona from plasma [38], and/or mixing BMNPs and MNPs [39]. ) in female BALB/c mice, analyzed 3 and 5 days after one single injection of DOXO-BMNPs or not functionalized BMNPs ± AMF: Each group received one intratumor injection of 3 mg BMNPs/mouse on the first day of the treatment (day 0).…”

Improving the Cellular Uptake of Biomimetic Magnetic Nanoparticles

“…On one hand, their nano scale size makes them display a larger surface area that allows them to carry relatively large amounts of the relevant molecule. On the other hand, their magnetic properties allow an external guidance and/or concentration at the target site plus the combination of therapies, such as targeted drug delivery and magnetic hyperthermia [ 2 , 3 , 4 , 5 ].…”