Oncolytic adenovirus-loaded magnetic-driven Janus tumor cell robots for active and targeted virotherapy of homologous carcinoma

Abstract

This work presents oncolytic adenovirus (OA)-loaded Janus tumor cell-based microrobots fabricated by asymmetrically coating OA-infected tumor cells with Fe3O4 nanoparticles (NPs), capable of homologous adhesion, active virotherapy, and magnetic navigation in complex topography. The cellular resources allow the infected OA to replicate inside the host cell, further inducing cytolysis to release the viral progeny for persistent and specific tumor infection and killing. The resulting cell robots preserve the intrinsic feature of tumor cells with cognate adhesion to homologous cancerous cells. The effective magnetic propulsion coupling with homologous binding of Janus cell robots greatly enhance their binding and penetration to three-dimensional (3D) homologous tumor cell spheroid with improved cell-killing efficacy. Moreover, cell robots can be navigated across the confined space and migrate from the bladder to the renal area through the ureter in the excised rabbit urinary system upon magnetic manipulation. Imparting tumor cells with magnetic propulsion force and virus cargos generates a motile therapeutic platform with the capability of tumor-specific killing and binding, and robust and steerable motion, holding great potential to cross the inherent barriers inside living body and achieve efficient drug delivery toward hard-to-reach sites upon minimized invasion and toxicity to healthy tissues.