Bacterial Minicell-Based Biohybrid Sub-micron Swimmers for Targeted Cargo Delivery

Bacterial biohybrid microrobots possess significant potential for targeted cargo delivery and minimally invasive therapy. However, many challenges, such as biocompatibility, stability, and effective cargo loading, remain. Bacterial membrane vesicles, also referred to as minicells, offer a promising alternative for creating sub-micron scale biohybrid swimmers (minicell biohybrids) due to their active metabolism, non-dividing nature, robust structure, and high cargo-carrying capacity. Here, a biohybrid system is reported that utilizes motile minicells, ≈400 nm in diameter, generated by aberrant cell division of engineered Escherichia coli (E. coli), for the first time. Achieving over 99% purification from their parental bacterial cells, minicells are functionalized with magnetic nanoparticles (MNPs) to enable external magnetic control. Minicell biohybrids are capable of swimming at an average speed of up to 13.3 µm s^-1 and being steered under a uniform magnetic field of 26 mT. Furthermore, they exhibit a significantly high drug loading capacity (2.8 µg mL^-1) while maintaining their motility and show pH-sensitive release of anticancer drug doxorubicin hydrochloride (DOX) under acidic conditions. Additionally, drug-loaded minicell biohybrids notably reduce the viability of SK-BR-3 breast cancer cells in vitro. This study introduces minicell biohybrids and establishes their potential as magnetically guided, drug-loaded biohybrid systems for targeted therapies in future medical applications.