DroneMTB · Directed and Responsive Oncology Nanoparticle-releasing microrobots from Engineered MagnetoTactic Bacteria

Given the prevalence of cancer, it is of utmost importance to develop new strategies to treat it. One of the most ambitious approaches is the use of microrobots, self-propelled microscopic devices capable of propelling themselves and being guided towards tumours where they can then effectuate a therapeutic action. Magnetotactic bacteria (MTB) are non-pathogenic aquatic microorganisms that synthesize intracellular magnetite nanoparticles within organelles called magnetosomes, and are ideal candidates to serve as microrobots for cancer theranostics. Suitably, they are highly motile, have preference for low oxygen conditions such as the inside of tumours, and can be externally guided, detected, and actuated by magnetic fields thanks to their chain of magnetosomes.In this project I propose a new approach to boost the therapeutic abilities of MTB by genetically engineering MTB to express immunotherapy-mediators on the surface of magnetosomes, and to create a triggered-release mechanisms to deliver these magnetosomes within the tumour microenvironment. This strategy, yet to be exploited, is more sustainable and cost-effective than the chemical-based approaches proposed to date. Specifically, new generations of MTB will maintain the genetic modifications without further need of surface modification or therapeutic loading steps. The perfomance and effectiveness of genetically modified MTB to swim towards and release the immunotherapy-mediating magnetosomes will be tested in vitro in 3D cancer cell models placed within microfluidic devices to mimic tumours and surrounding vasculature.DroneMTB is a highly interdisciplinary project that combines methods from materials science, microbiology, genetic engineering, biochemistry, microfluidics, microscopy, and cell biology. After carrying out the project I will have acquired necessary skills to become an independent scientist and to lead research projects in the field of biomaterials and biomedical applications.