Motion for Medicine: Enzyme-Driven Active Systems for Drug Delivery

Enzyme-driven micro/nanomotors (MNMs), a prominent class of active matter systems, have been extensively studied over the past two decades for their unique dynamics in substrate-rich media and their potential for biomedical applications such as cargo delivery and sensing. A wide variety of motors have been fabricated with diverse shapes, sizes, chassis materials, and enzyme immobilization strategies. While a large number of reviews have focused on the current developments of these motors, this Review examines several promising research directions that have, to date, received relatively little attention. We highlight several fundamental studies that are still needed to determine the efficacy of these motors over extended operation periods in vivo. This Review also discusses the need to understand how enzyme orientation and surface distribution evolve during motor operation and influence MNM dynamics. Challenges encountered by enzyme-coated MNMs in biological environments, such as long-term operational stability and enzyme coating lifetime, may be addressed through the incorporation of smart responsive materials for the motor chassis and the development of multifunctional motors. Most importantly, expanding the enzyme library beyond the few used so far, such as catalase and urease, to include enzymes with bioavailable substrates and clinical relevance could drive a paradigm shift in the development of MNMs with promising therapeutic applications. We also highlight the challenges the motors are likely to encounter following in vivo administration, including crossing biological barriers in different parts of the body. Lastly, we provide a roadmap to guide the development of enzyme-coated MNMs for realistic and efficient biomedical applications.