Functionalized biomimetic magnetic nanoparticles as effective nanocarriers for targeted chemotherapy
Francesca Oltolina1, Ana Peigneux2, Concepcion Jimenez-Lopez2, Maria Prat1,3
1 Dept. Health Sciences, Università del Piemonte Orientale, Novara, Italy, 2 Dept. de Microbiología, Facultad de Ciencias, Universidad de Granada, Granada, Spain, 3 Centro di Biotecnologie per la Ricerca Medica Applicata (BRMA), Novara, Italy
Nanotechnology and nanoparticles (NPs) are becoming very attractive for their applications in different fields, comprising biology, medicine and oncology in particular. In this context, magnetite nanoparticles are even more interesting, since besides being multifunctional platforms, they can be manipulated by an external magnetic field, either continuous, which can direct them at peculiar chosen sites, or alternating, which can mediate hyperthermic ablation.
Herein, we describe a drug delivery system based on biomimetic magnetic nanoparticles (BMNPs) synthetized in presence of MamC protein from Magnetococcus marinus MC-1. This protein controls the morphology and size of the crystals, producing well faceted BMNPs of ~40 nm that are paramagnetic at room and body temperature while having a large magnetic moment per particle under an external magnetic field. Because of this protein, BMNPs have a negative surface charge at physiological pH values that allow an efficient coupling with different molecules. These BMNPs were functionalized with the DO-24 monoclonal antibody (mAb) directed against the ectodomain of the human Met/HGF receptor (overexpressed in many cancers) and the chemotherapeutic drug doxorubicin (DOXO). Unfunctionalized or mAb-coupled BMNPs were cytocompatibles while the DOXO-functionalized complexes were cytotoxic. DOXO-mAb-BMNPs discharged the drug within the cell nuclei more efficiently in cell overexpressing Met/HGFR and this effect was enhanced by the application of a continuous magnetic field.
When BMNPs were injected i.v.in mice, they showed high biocompatibility, since no organ morphological alterations were observed. Moreover, when DOXO-functionalized or not functionalized BMNPs were i.v. injected in mice bearing 4T1 induced mammary carcinomas, the application of the magnet on the tumor for 1 hour reduced the tumor size and this effect was enhanced by the presence of DOXO on BMNPs.
All together these data suggest that the controlled dual targeting (mAb-mediated and magnetic) exerted by the BMNPs on tumors could represent a promising approach for cancer therapy. Least, but not last, BMNPs could be exploited also for thermoablation.
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