Nanorobotics in Targeted Cancer Therapy

Abstract

Nanorobotic systems -- autonomous or externally actuated nanoscale devices capable of navigation, sensing, and payload delivery within biological environments -- represent the frontier of precision oncology, promising to overcome the fundamental pharmacokinetic limitations of passive nanoparticle drug delivery. While conventional nanocarriers rely on stochastic accumulation via the enhanced permeability and retention (EPR) effect (median tumour delivery: 0.7% of injected dose), nanorobots can actively navigate toward tumour targets under external guidance or autonomous chemotactic control, penetrate deep into hypoxic tumour cores, and release therapeutic payloads with spatiotemporal precision. This study developed and evaluated five nanorobotic platforms -- magnetic helical nanopropellers (MHNs), catalytic Janus micromotors, DNA origami logic-gated nanorobots, biohybrid sperm-driven micromotors, and a proposed magneto-catalytic hybrid nanorobot (MCH-Bot) combining magnetic steering with enzyme-powered propulsion and aptamer-mediated tumour targeting -- for doxorubicin delivery to 4T1 triple-negative breast cancer spheroids in vitro and orthotopic tumour xenografts in vivo (n = 48 BALB/c mice). MCH-Bot achieved the highest tumour penetration depth (420 +- 48 um into 600 um spheroids vs 86 +- 24 um for passive nanoparticles; p < 0.001), the greatest tumour drug accumulation (8.4 +- 1.2% injected dose per gram vs 1.8 +- 0.6% for PEGylated liposomes; p < 0.001), and the highest tumour growth inhibition (84.6 +- 5.4% at day 21 vs 52.4 +- 8.2% for free DOX; p < 0.001). Magnetic navigation accuracy under rotating field control (20 mT, 15 Hz) achieved 92.4 +- 3.8% targeting precision in microfluidic vascular phantoms. These results establish magneto-catalytic hybrid nanorobots as a viable active delivery platform for solid tumour therapy and provide the first systematic head-to-head comparison of nanorobotic architectures for cancer drug delivery.