Can Bottom-Up Synthetic Biology Generate Advanced Drug-Delivery Systems?

Abstract

Nanomedicine has demonstrated the potential of nanotechnology in treating diseases by selectively targeting pathogenic cells and releasing their cargo on site, but the complexity of molecular engineering such drug-delivery vehicles impedes their broad application and clinical translation. New methodologies to generate more advanced and intelligent systems are required.Bottom-up synthetic biology, empowered by microfluidics, allows the conception of multifunctional cell-mimicking structures – such as synthetic exosomes – that showcase its ability to create sophisticated systems.Recently, considerable progress has been made towards the assembly of complex structures that can dynamically release therapeutics, sustain protein biosynthesis, and sense and interact with the nearby environment. These functionalities will propel the creation of advanced drug-delivery platforms. Creating a magic bullet that can selectively kill cancer cells while sparing nearby healthy cells remains one of the most ambitious objectives in pharmacology. Nanomedicine, which relies on the use of nanotechnologies to fight disease, was envisaged to fulfill this coveted goal. Despite substantial progress, the structural complexity of therapeutic vehicles impedes their broad clinical application. Novel modular manufacturing approaches for engineering programmable drug carriers may be able to overcome some fundamental limitations of nanomedicine. We discuss how bottom-up synthetic biology principles, empowered by microfluidics, can palliate current drug carrier assembly limitations, and we demonstrate how such a magic bullet could be engineered from the bottom up to ultimately improve clinical outcomes for patients. Creating a magic bullet that can selectively kill cancer cells while sparing nearby healthy cells remains one of the most ambitious objectives in pharmacology. Nanomedicine, which relies on the use of nanotechnologies to fight disease, was envisaged to fulfill this coveted goal. Despite substantial progress, the structural complexity of therapeutic vehicles impedes their broad clinical application. Novel modular manufacturing approaches for engineering programmable drug carriers may be able to overcome some fundamental limitations of nanomedicine. We discuss how bottom-up synthetic biology principles, empowered by microfluidics, can palliate current drug carrier assembly limitations, and we demonstrate how such a magic bullet could be engineered from the bottom up to ultimately improve clinical outcomes for patients. Paul Ehrlich, considered to be the pioneer and founder of modern chemotherapy, envisaged a therapeutic capable of directly interreacting with its intended disease-causing cellular structure while remaining harmless to the surrounding healthy cell population. Depicted as a magic bullet, his idea has greatly influenced and fascinated various fields of science for more than a century [1.Strebhardt K. Ullrich A. Paul Ehrlich's magic bullet concept: 100 years of progress.Nat. Rev. Cancer. 2008; 8: 473-480Crossref PubMed Scopus (747) Google Scholar]. Among them, the field of nanomedicine (see Glossary) – which relies on nanotechnologies to improve passive and active accumulation of drugs nearby target pathogens or cell populations – was expected to achieve this highly coveted goal. Despite its major focus on oncology, nanomedicine has also triggered the engineering of an arsenal of novel nanotechnologies and functionalization strategies. Overall, these innovations have resulted in a variety of enhanced bio- and physico-chemical properties for inorganic-, polymer-, and lipid-based nanometric carriers. 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