Magnetic iron oxide nanoparticles (MNP) hold great promise for biomedical applications such as targeted drug delivery, imaging (magnetic resonance imaging, MRI, and magnetic particle imaging, MPI), and cancer treatment via hyperthermia. Their effectiveness depends on precise physical and chemical properties - especially size, shape, and crystallinity - which influence both magnetic behavior and biological interactions. Different applications require different particle sizes: superparamagnetic particles under 30 nm are ideal for drug delivery, while larger particles (35 - 40 nm) are better for hyperthermia. For magnetic imaging, optimal sizes vary, with MPI requiring highly specific magnetic characteristics in addition to size constraints. Current chemical synthesis methods struggle to produce uniform, biocompatible MNPs with tailored properties, often resulting in inconsistent quality and potential toxicity due to chemical residuals. Thus, in principle, the reliable production of multifunctional, high-performance MNPs has remained an unresolved challenge.
Magnetotactic bacteria (MTB) naturally produce magnetic nanoparticles (magnetosomes) with superior properties - uniform size, high crystallinity and strong magnetization. Unlike chemically synthesized MNPs, magnetosomes possess a genetically encoded blueprint and can be precisely engineered for specific functions. Their biological membrane envelope can be harnessed to anchor a wide spectrum of functional moieties to their surface by genetic means, a substantial advantage for the generation of versatile “theranostic” (both diagnostic and therapeutic) MNP. Thus, these biogenic MNP particles offer a level of precision and versatility that synthetic methods cannot match.
However, purification of magnetosomes in high yield from native MTB poses challenges due to cumbersome cultivation and low productivity of these strains. One of the main achievements of earlier ERC-funded research in our AdG-project Syntomagx was the successful transplantation of the complex biosynthetic pathway for magnetosomes from native MTB to novel host microbial host organisms, among them several biotechnologically more amenable strains. Syntomagx has also laid the technological groundwork for the creation of designer MNP with customizable features, such as enzyme or antibody attachments.
The aim of the present project, BacToMagicle, was to unlock the commercial potential of high-quality magnetic nanoparticles from bioengineered, synthetically magnetized bacteria (SynBacMag) by testing scalability of their production and validating their performance and safety in clinical imaging applications like MPI.
