Biohybrid Microrobots Based on Jellyfish Stinging Capsules and Janus Particles for In Vitro Deep-Tissue Drug Penetration.

Abstract

Microrobots engineered from self-propelling active particles extend the reach of robotic operations to submillimeter dimensions and are becoming increasingly relevant for various tasks, such as manipulation of micro/nanoscale cargo, particularly targeted drug delivery. However, achieving deep-tissue penetration and drug delivery remains a challenge. This work develops a novel biohybrid microrobot consisting of jellyfish-stinging capsules, which act as natural nanoinjectors for efficient penetration and delivery, assembled onto an active Janus particle (JP). While microrobot transport and navigation is externally controlled by magnetic field-induced rolling, capsule loading onto the JP surface is controlled by electric field. Following precise navigation of the biohybrid microrobots to the vicinity of target tissues, the capsules are activated by a specific enzyme introduced to the solution, which then triggers tubule ejection and release of the preloaded molecules. Use of such microrobots for penetration of and delivery of the preloaded drug/toxin to targeted cancer spheroids and live Caenorhabditis elegans is demonstrated in vitro. The findings offer insights for future development of bioinspired microrobots capable of deep penetration and drug delivery. Future directions may involve encapsulation of various drugs within different capsule types for enhanced versatility. This study may also inspire in vivo applications involving deep tissue drug delivery.