High-performance, multifunctional bacteria-driven microswimmers are introduced using an optimized design and fabrication method for targeted drug delivery applications. These microswimmers are made of mostly single Escherichia coli bacterium attached to the surface of drug-loaded polyelectrolyte multilayer (PEM) microparticles with embedded magnetic nanoparticles. The PEM drug carriers are 1 μm in diameter and are intentionally fabricated with a more viscoelastic material than the particles previously studied in the literature. The resulting stochastic microswimmers are able to swim at mean speeds of up to 22.5 μm/s. They can be guided and targeted to specific cells, because they exhibit biased and directional motion under a chemoattractant gradient and a magnetic field, respectively. Moreover, we demonstrate the microswimmers delivering doxorubicin anticancer drug molecules, encapsulated in the polyelectrolyte multilayers, to 4T1 breast cancer cells under magnetic guidance in vitro. The results reveal the feasibility of using these active multifunctional bacteria-driven microswimmers to perform targeted drug delivery with significantly enhanced drug transfer, when compared with the passive PEM microparticles.

Articles you may be interested inMultiple-robot drug delivery strategy through coordinated teams of microswimmers Appl. Phys. Lett. 105, 083705 (2014); 10.1063/1.4893695Magnetic approaches to study collective three-dimensional cell mechanics in long-term cultures (invited)

Bio-hybrid devices, which integrate biological cells with synthetic components, have opened a new path in miniaturized systems with the potential to provide actuation and control for systems down to a few microns in size. Here, we address the challenge of remotely controlling bio-hybrid microswimmers propelled by multiple bacterial cells. These devices have been proposed as a viable method for targeted drug delivery but have also been shown to exhibit stochastic motion. We demonstrate a method of remote magnetic control that significantly reduces the stochasticity of the motion, enabling steering control. The demonstrated microswimmers consist of multiple Serratia marcescens (S. marcescens) bacteria attached to a 6 μm-diameter superparamagnetic bead. We characterize their motion and define the parameters governing their controllability. We show that the microswimmers can be controlled along two-dimensional (2-D) trajectories using weak magnetic fields (≤10 mT) and can achieve 2-D swimming speeds up to 7.3 μm s(-1). This magnetic steering approach can be integrated with sensory-based steering in future work, enabling new control strategies for bio-hybrid microsystems.

The tumor suppressor gene BRCA1 maintains genomic integrity by protecting cells from the deleterious effects of DNA double-strand breaks (DSBs). Through its interactions with the checkpoint kinase 2 (Chk2) kinase and Rad51, BRCA1 promotes homologous recombination, which is typically an error-free repair process. In addition, accumulating evidence implicates BRCA1 in the regulation of nonhomologous endjoining (NHEJ), which may involve precise religation of the DSB ends if they are compatible (i.e., error-free repair) or sequence alteration upon rejoining (i.e., error-prone or mutagenic repair). However, the precise role of BRCA1 in regulating these different subtypes of NHEJ is not clear. We provide here the genetic and biochemical evidence to show that BRCA1 promotes error-free rejoining of DSBs in human breast carcinoma cells while suppressing microhomologymediated error-prone end-joining and restricting sequence deletion at the break junction during repair. The repair spectrum in BRCA1-deficient cells was characterized by an increase in the formation of >2 kb deletions and in the usage of long microhomologies distal to the break site, compared with wild-type (WT) cells. This error-prone repair phenotype could also be revealed by disruption of the Chk2 phosphorylation site of BRCA1, or by expression of a dominant-negative kinase-dead Chk2 mutant in cells with WT BRCA1. We suggest that the differential control of NHEJ subprocesses by BRCA1, in concert with Chk2, reduces the mutagenic potential of NHEJ, thereby contributing to the prevention of familial breast