Enzyme-powered Janus platelet cell robots for active and targeted drug delivery

Abstract

Transforming natural cells into functional biocompatible robots capable of active movement is expected to enhance the functions of the cells and revolutionize the development of synthetic micromotors. However, present cell-based micromotor systems commonly require the propulsion capabilities of rigid motors, external fields, or harsh conditions, which may compromise biocompatibility and require complex actuation equipment. Here, we report on an endogenous enzyme-powered Janus platelet micromotor (JPL-motor) system prepared by immobilizing urease asymmetrically onto the surface of natural platelet cells. This Janus distribution of urease on platelet cells enables uneven decomposition of urea in biofluids to generate enhanced chemophoretic motion. The cell surface engineering with urease has negligible impact on the functional surface proteins of platelets, and hence, the resulting JPL-motors preserve the intrinsic biofunctionalities of platelets, including effective targeting of cancer cells and bacteria. The efficient propulsion of JPL-motors in the presence of the urea fuel greatly enhances their binding efficiency with these biological targets and improves their therapeutic efficacy when loaded with model anticancer or antibiotic drugs. Overall, asymmetric enzyme immobilization on the platelet surface leads to a biogenic microrobotic system capable of autonomous movement using biological fuel. The ability to impart self-propulsion onto biological cells, such as platelets, and to load these cellular robots with a variety of functional components holds considerable promise for developing multifunctional cell-based micromotors for a variety of biomedical applications.

Medical Micro/Nanorobots in Precision Medicine

“…[184,185] More recently, a fully organic microrobot consisting of urease-powered Janus platelet micromotor was engineered by immobilizing enzyme onto the surface of natural platelet cells toward selective adhesion to cancer cells and subsequent delivery of doxorubicin. [186] Microorganism-driven micro/nanorobots have also been used as targeted drug delivery systems. Motile sperm loaded with doxorubicin were integrated into a 3D-printed magnetic tubular microstructure that permitted magnetic guidance and assistance to push against the tumor site.…”

<p>Size-Dependent Antibacterial Immunity of <em>Staphylococcus aureus</em> Protoplast-Derived Particulate Vaccines</p>

“…Altogether, the elevated production of IFN-γ but not IL-4 suggested strong Th1 biased cell responses against the S. aureus bacteria infection. [43][44][45] On the contrary, Th2 biased cell response are usually associated with extracellular parasite infections or asthma, which was not activated by PDNVs immunization.…”

Cell‐Membrane‐Display Nanotechnology

“…[120] There are also natural cell motors, which are biocompatible and capable of active movement, utilize the ability of urease to catalyze the hydrolysis of urea as biofuel and generate effective propulsion forces in the presence of urea containing biological fluids. [121] In recent years, cell-membrane-display nanotechnology can be utilized to modify nanomotors to bestow them with celllike functions. [122] To bestow nanomotors with dual membrane functions, including the toxin neutralization of RBC membranes and the pathogen-binding ability of platelet membranes, de Ávila et al constructed a hybrid membrane of RBC and platelets through 5 min ultrasonication and coated them onto acoustic gold nanowires (AuNWs).…”