Active micro- and nanorobots for controlled immune modulation in protected pathological niches.

Immune therapies often underperform in anatomically protected sites. Dense tumour stroma, mucus, biofilms, fibrin-rich matrices and intracellular compartments can prevent an intervention from reaching the cells that determine outcome. Organ-level exposure may still be measurable. Conventional nanocarriers improve cargo stability and biodistribution, but usually provide little control after deposition. Micro- and nanorobotic systems add propulsion, steering, mechanical work or triggered release. Their value depends on the bottleneck being addressed and on the performance of the best matched passive or regional comparator. This Review asks three linked questions. Can the platform cross the relevant barrier? Can it increase productive encounters with target cells? Can it control the timing and location of immune activation? We distinguish direct immune-modulation evidence, immune-relevant delivery evidence and contextual benchmark evidence. We also use an author-proposed framework to assess support for each stated claim. Current evidence favours local redistribution, matrix disruption and gated stimulation over systemic navigation or motion-dependent immune causality. Recurrent gaps include actuation-off controls, matched carriers, active-fraction measurements, propulsion-lifetime measurements and explicit dose definitions. Active delivery is most credible when it solves a defined transport problem in an accessible or regionally treatable niche. In other settings, its added complexity remains insufficiently justified.