Multifunctional surface microrollers for targeted cargo delivery in physiological blood flow

Abstract

Mobile microrobots offer great promise for minimally invasive targeted medical theranostic applications at hard-to-access regions inside the human body. The circulatory system represents the ideal route for navigation; however, blood flow impairs propulsion of microrobots especially for the ones with overall sizes less than 10 micrometers. Moreover, cell- and tissue-specific targeting is required for efficient recognition of disease sites and long-term preservation of microrobots under dynamic flow conditions. Here, we report cell-sized multifunctional surface microrollers with similar to 3.0 and similar to 7.8-micrometer diameters, inspired by leukocytes in the circulatory system, for targeted drug delivery into specific cells and controlled navigation inside blood flow. The leukocyte-inspired spherical microrollers are composed of magnetically responsive Janus microparticles functionalized with targeting antibodies against cancer cells (anti-HER2) and light-cleavable cancer drug molecules (doxorubicin). Magnetic propulsion and steering of the microrollers resulted in translational motion speeds up to 600 micrometers per second, around 76 body lengths per second. Targeting cancer cells among a heterogeneous cell population was demonstrated by active propulsion and steering of the microrollers over the cell monolayers. The multifunctional microrollers were propelled against physiologically relevant blood flow (up to 2.5 dynes per square centimeter) on planar and endothelialized microchannels. Furthermore, the microrollers generated sufficient upstream propulsion to locomote on inclined three-dimensional surfaces in physiologically relevant blood flow. The multifunctional microroller platform described here presents a bioinspired approach toward in vivo controlled propulsion, navigation, and targeted active cargo delivery in the circulatory system.