Achieving the targeted retention of nanomotors via a controllable "braking" mechanism based on molecularly programmed...

Nanomotors have unique autonomous mobility capabilities, offering significant advantages for promoting deep penetration of drugs into pathological sites. However, achieving on-demand "braking" and active retention within target areas remains a critical challenge for efficient, intelligent delivery. The absence of controllable braking mechanisms may cause the nanomotor to continue moving and rapidly dissipate after reaching the target site, hindering effective local enrichment and sustained therapy. In this study, a peptide nucleic acid (PNA)-triggered, in vivo-controlled, engine-disassembly-based active braking mechanism is proposed for nanomotors. This nanomotor anchors the different catalytic engine (catalase, urease, glucose oxidase, and Pt) to the carrier surface via programmable PNA complementary, thus accommodating various application scenarios. After reaching the target area and achieving deep penetration, the injected exogenous complementary chains competitively displace the engine, triggering precise "braking." This braking mechanism relies on PNA sequence-specific base-complementary pairing and competitive displacement, enabling on-demand braking in vivo. Experimental results demonstrate that the drug-loaded nanomotor exhibits excellent tumor-targeting accumulation and tissue penetration capabilities in tumor-bearing mouse models. Following the intravenous injection of PNA to trigger braking, it produces the strongest tumor suppression effect. This study provides a novel strategy for developing intelligent nanomotor therapeutic systems that combine deep penetration with long-lasting retention capabilities.