Scalable liposomes functionalization via membrane lipid exchange mechanisms

Abstract

Extracellular vesicles are pivotal in intercellular communication and hold significant promise for medical applications. However, limitations in their mass production and challenges in replicating their complex functions with artificial liposomes necessitate innovative solutions. We functionalize liposomes by combining the scalable production advantages of artificial liposomes with the vesicle fusion and formation mechanisms of bacteria. By incubating the gram-negative Shewanella oneidensis MR-1, known for its electrochemically active outer membrane cytochromes (OMCs), with liposomes containing 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine for 24 hours, we achieved a substantial yield of membrane-integrated liposomes (MILs) incorporating OMCs. Circular dichroism spectroscopy confirmed the preservation of redox activity and strong inter-heme exciton coupling in the OMCs. These components were successfully delivered to Escherichia coli K-12 by incubation with MILs, retaining their functionality. Furthermore, the slow membrane exchange process did not result in cellular viability loss or lysis, allowing for the recycling of microbial cells and minimizing contaminants from lysed cells, which is advantageous for scaling up. Building on our previous work where MIL-coated titanium dioxide nanoparticles significantly enhanced radical production and effectively treated orthotopic liver tumors in vivo, our methodology to generate the MIL has promising potential to spearhead novel integrations of synthetic and biological systems for medical technologies.