Bacteria-driven biohybrid microswimmers (bacteriabots) combine synthetic cargo with motile living bacteria that enable propulsion and steering. Although fabrication and potential use of such bacteriabots have attracted much attention, existing methods of fabrication require an extensive sample preparation that can drastically decrease the viability and motility of bacteria. Moreover, chemotactic behavior of bacteriabots in a liquid medium with chemical gradients has remained largely unclear. To overcome these shortcomings, we designed Escherichia coli to autonomously display biotin on its cell surface via the engineered autotransporter antigen 43 and thus to bind streptavidin-coated cargo. We show that the cargo attachment to these bacteria is greatly enhanced by motility and occurs predominantly at the cell poles, which is greatly beneficial for the fabrication of motile bacteriabots. We further performed a systemic study to understand and optimize the ability of these bacteriabots to follow chemical gradients. We demonstrate that the chemotaxis of bacteriabots is primarily limited by the cargo-dependent reduction of swimming speed and show that the fabrication of bacteriabots using elongated E. coli cells can be used to overcome this limitation.

Bacteria-driven biohybrid microswimmers (bacteriabots), which integrate motile bacterial cells and functional synthetic cargo parts (e.g., microparticles encapsulating drug), are recently studied for targeted drug delivery. However, adhesion of such bacteriabots to the tissues on the site of a disease (which can increase the drug delivery efficiency) is not studied yet. Here, this paper proposes an approach to attach bacteriabots to certain types of epithelial cells (expressing mannose on the membrane), based on the affinity between lectin molecules on the tip of bacterial type I pili and mannose molecules on the epithelial cells. It is shown that the bacteria can anchor their cargo particles to mannose-functionalized surfaces and mannose-expressing cells (ATCC HTB-9) using the lectin–mannose bond. The attachment mechanism is confirmed by comparing the adhesion of bacteriabots fabricated from bacterial strains with or without type I pili to mannose-covered surfaces and cells. The proposed bioadhesive motile system can be further improved by expressing more specific adhesion moieties on the membrane of the bacteria.

There is a growing interest in transdermal delivery systems because of their noninvasive, targeted, and on-demand delivery of gene and drugs. However, efficient penetration of therapeutic compounds into the skin is still challenging largely due to the impermeability of the outermost layer of the skin, known as stratum corneum. Recently, there have been major research activities to enhance the skin penetration depth of pharmacological agents. This article reviews recent advances in the development of various strategies for skin penetration enhancement. We show that approaches such as ultrasound waves, laser, and microneedle patches have successfully been employed to physically disrupt the stratum corneum structure for enhanced transdermal delivery. Rather than physical approaches, several non-physical route have also been utilized for efficient transdermal delivery across the skin barrier. Finally, we discuss some clinical applications of transdermal delivery systems for gene and drug delivery. This paper shows that transdermal delivery devices can potentially function for diverse healthcare and medical applications while further investigations are still necessary for more efficient skin penetration of gene and drugs.

The use of bacterial cells as agents of medical therapy has a long history. Research that was ignited over a century ago with the accidental infection of cancer patients has matured into a platform technology that offers the promise of opening up new potential frontiers in medical treatment. Bacterial cells exhibit unique characteristics that make them well-suited as smart drug delivery agents. Our ability to genetically manipulate the molecular machinery of these cells enables the customization of their therapeutic action as well as its precise tuning and spatio-temporal control, allowing for the design of unique, complex therapeutic functions, unmatched by current drug delivery systems. Early results have been promising, but there are still many important challenges that must be addressed. We present a review of promises and challenges of employing bioengineered bacteria in drug delivery systems and introduce the biohybrid design concept as a new additional paradigm in bacteria-based drug delivery.