Improving extracellular matrix penetration with biocatalytic metal-organic framework nanomotors

Abstract

The development of self-propelled nanomotors offers a promising strategy to enhance targeted drug delivery efficiency in cancer therapy. Active motion is believed to aid nanomotors in overcoming the physical barriers of the tumor microenvironment, allowing for deep tissue penetration; however, this crucial concept lacks detailed mechanistic understanding. In this study, we report catalase and collagenase dual-enzyme functionalized Zeolitic Imidazolate Framework-90 (ZIF-90) nanomotors. Catalase enables the nanomotors with self-propulsion in the presence of low amount of hydrogen peroxide, while collagenase enables catalytic decomposition of collagen, a major component of the extracellular matrix (ECM), thereby enhancing motility and facilitating deeper penetration into the ECM. Experimental and computational studies elucidated the detailed mechanisms governing ECM penetration kinetics. Using a three-dimensional tumor spheroid model, the nanomotors demonstrated enhanced tissue penetration, leading to improved drug delivery and a significant reduction in cell viability. These findings underscore the potential of self-propelled nanomotors to improve drug delivery efficiency in solid tumors by leveraging both biocatalytic activity and active motion to navigate biological barriers.