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BIOMAG

Biomimetic Magnetic NanoParticles comprising magnetosome proteins

Description

Our technology consists on producing and functionalizing Biomimetic Magnetic NanoParticles (BMNPs), recently patented. These novel magnetic nanoparticles, composed of magnetite (Fe3O4), are produced by taking inspiration from nature, in particular, from the magnetosomes produced by magnetotactic bacteria.

These bacteria have optimized the production of single domain magnetic nanoparticles thought an exquisitely genetically controlled process in order to confer these nanoparticles with novel and specific features that maximize their sensing to an external magnetic field.

The novelty of BMNPs compared to traditional MNPs lies on changes on the size, magnetic properties, and surface properties of the former. These new characteristics of BMNPs are induced by the control over magnetite precipitation exerted by the protein MamC, a magnetosome-associated protein of Magnetococcus marinus MC-1, which is introduced in the reaction mixture from which magnetite forms. MamC chelates Fe cations and acts as template for magnetite nucleation (Ubago et al., 2019), which, in turn, results in superparamagnetic BMNPs nanoparticles, larger (35-40 nm) than those MNPs chemically produced (<20 nm). The size increase allows BMNPs to be superparamagnetic and to display a larger magnetic moment per particle than that displayed by MNPs. This characteristic ensures an enhanced magnetic response once an external magnetic field is applied for guidance and/or concentration, and favors a non-magnetic behavior of BMNPs in the absence of an external magnetic field which prevents BMNPs aggregation (García Rubia et al., 2018).

In terms of surface charge, the advantage of using BMNPs versus MNPs is mainly related to the greater ease in the process of functionalization. MNPs usually have an isoelectric point close to 7, thus they need to be coated to successfully bind the relevant molecule and to keep stable the nano-assembly at physiological pH. Instead, in the case of BMNPs, MamC confers to the nanoparticles surface functional groups, which switch their isoelectric point to 4.5 (García Rubia et al., 2018; Peigneux et al., 2019). This is important, since being the nanoparticle negatively charged at physiological pH, drug binding by electrostatic interaction and nano-assembly stability at this pH value is ensured, while drug release is triggered in acidic environments (as those related to tumors and many bacterial infections), as BMNPs become uncharged, BMNPs behaving as a stimulus-response drug delivery system. Furthermore, BMNPs are hyperthermia agents, able to locally raise the temperature to the hyperthermia therapeutic range (41-45°C) following upon the application of an alternating magnetic field (AMF) or to laser in the NIR, which, moreover, further increases drug release at the target (i.e., papers from Jabalera et al., listed in the references].

MamC-mediated BMNPs are cytocompatible and have proven in vivo (mice model) to be suitable nanocarriers for a directed combined therapy (Oltolina et al., 2020). Moreover, they can be embedded in liposomes (Jabalera et al., 2020; Garcia-Pinel et al., 2020) or in PLGA (Vurro et al., 2020) maintaining their functionality and ability for a directed chemotherapy combined with hyperthermia.

Current needs

This program has been designed with disruptive biotech and medtech start-ups in mind. The team of mentors is acquinted with this kind of start-up, and what are the main barriers to success. The program has been designed with all this experience in mind.

Meet the team

Actuación del Campus de excelencia cofinanciadas por la Unión Europea a través del Fondo Europeo de Desarrollo Regional (FEDER) y la Consejería de Economía, Conocimiento, Empresas y Universidad, Junta de Andalucía.

Proyecto Singular ILIBERIS: Actuaciones Singulares de Transferencia de Conocimiento en el CEI BIOTIC.

Marco por el que se impulsa el desarrollo de Proyectos Singulares de actuaciones de transferencia en los Campus de Excelencia Internacional en las áreas de la Estrategia de Investigación e Innovación para la Especialización Inteligente de Andalucía (RIS3) con cargo al Programa Operativo FEDER 2014-2020 de Andalucía.