Engineered Bacteria with Genetic Circuits Accumulating Nanomagnets as MRI Contrast Agents

• Published in: Small (Weinheim an der Bergstrasse, Germany) Germany), 2022-07, Vol.18 (26), p.e2200537-n/a
• Main Authors: Yavuz, Merve, Ütkür, Mustafa, Kehribar, Ebru Şahin, Yağız, Ecrin, Sarıtaş, Emine Ülkü, Şeker, Urartu Özgür Şafak
• Format: Article
• Language: English
• Subjects: Accumulation; Bacteria; Binding; Biocompatibility; Biomedical materials; Cancer; Combinatorial analysis; Contrast agents; E coli; genetic circuits; Geomagnetic field; Hyperthermia; Iron; iron oxide nanoparticles; magnetic bacteria; Magnetic properties; Magnetic resonance imaging; magnetic resonance imaging contrast agents; Magnetite; Nanocrystals; nanomagnets; Nanoparticles; Nanotechnology; Peptides; Proteins; Side effects; synthetic biology
• ISSN: 1613-6810; 1613-6829
• DOI: 10.1002/smll.202200537

The demand for highly efficient cancer diagnostic tools increases alongside the high cancer incidence nowadays. Moreover, there is an imperative need for novel cancer treatment therapies that lack the side effects of conventional treatment options. Developments in this aspect employ magnetic nanoparticles (MNPs) for biomedical applications due to their stability, biocompatibility, and magnetic properties. Certain organisms, including many bacteria, can synthesize magnetic nanocrystals, which help their spatial orientation and survival by sensing the earth's geomagnetic field. This work aims to convert Escherichia coli to accumulate magnetite, which can further be coupled with drug delivery modules. The authors design magnetite accumulating bacterial machines using genetic circuitries hiring Mms6 with iron‐binding activity and essential in magnetite crystal formation. The work demonstrates that the combinatorial effect of Mms6 with ferroxidase, iron transporter protein, and material binding peptide enhances the paramagnetic behavior of the cells in magnetic resonance imaging (MRI) measurements. Cellular machines are also engineered to display Mms6 peptide on the cell surface via an autotransporter protein that shows augmented MRI performance. The findings are promising for endowing a probiotic bacterium, able to accumulate magnetite intracellularly or extracellularly, serving as a theranostics agent for cancer diagnostics via MRI scanning and hyperthermia treatment. By employing synthetic biology, Escherichia coli is engineered to harbor genetic circuitries for the purpose of accumulating magnetite crystals inside/on the cell surface as a potentially alternative way with minimal side effects to healthy cells to enhance in vivo cancer targeting for MRI imaging, hyperthermia, or drug delivery.