"Tethered interventions, such as aspiration catheters and stent retrievers, are the current standard for large‑vessel occlusion," explains Professor Ben Wang. "They offer stable positioning, rapid debulking and reliable retrieval. However, they cannot reach tortuous distal branches or the microcirculation, and dense, fibrin‑rich thrombi often resist treatment." Newer tethered devices address some of these limitations: the "milli‑spinner" thrombectomy device applies compressive and shear loading to compact a clot to about 10% of its original volume, enabling ultrafast removal even in pulmonary and cerebral arteries (in vitro and porcine studies). Ultrasound‑assisted catheter‑directed thrombolysis (USAT), such as the EKOS system, uses low‑energy acoustic waves to loosen fibrin bundles and improve drug penetration. In the ERASE PE registry, this approach reduced the right‑to‑left ventricular ratio from 1.41 to 1.03 with an in‑hospital mortality of only 3.2% and an intracranial hemorrhage rate of 1.0%. "But even these advanced catheters cannot resolve micro‑emboli that cause the 'no‑reflow' phenomenon," adds Professor Wang.
This is where untethered systems come in. "Injectable micro‑ and nanoscale carriers can be designed to circulate, target, penetrate and release thrombolytics on demand," says Professor Qinglong Wang. The review classifies six carrier classes – lipid‑based, polymer‑based, inorganic/nanomaterial, biomimetic, hydrogel and bubble‑based – each with distinct strengths. Lipid carriers prolong circulation, polymer systems enable stimulus‑responsive release, and biomimetic carriers (e.g., platelet‑membrane‑coated particles) leverage natural adhesion to fibrin. However, passive carriers alone cannot overcome the dense fibrin barrier. Therefore, the field is moving toward actively actuated micro/nanorobots powered by magnetic, acoustic or optical fields.
"Magnetic fields allow us to assemble a swarm of nanorobots that can stir, penetrate and mechanically disrupt the clot while delivering drugs," explains Professor Ben Wang. For example, heparinoid‑polymer‑brush‑grafted magnetic nanorobots form navigable swarms under a rotating field, enhancing thrombolysis and then disassembling for safer clearance. In a striking demonstration, Fe₃O₄@mSiO₂ nanorobots loaded with tPA are released from a catheter, assembled into a microswarm by an external magnetic field, and guided into submillimeter M3/M4 branches to achieve recanalization that would otherwise be impossible. After treatment, the swarm is aspirated back – an integrated "deliver, amplify, retrieve" workflow.
Ultrasound offers another powerful tool. Nanoparticle‑shelled microbubbles can be triggered by diagnostic ultrasound to cavitate, creating microjets that physically loosen the thrombus and drive drugs deep inside. "This is a true closed‑loop approach: ultrasound localizes the clot, activates the carriers, and simultaneously monitors the therapy," notes Professor Qinglong Wang. Optical (near‑infrared) systems provide precise local heating to soften fibrin and enhance drug diffusion, though their depth penetration is limited.
Imaging is the glue that ties tethered and untethered strategies together. "Closed‑loop control requires real‑time feedback on thrombus burden, device position and treatment response," says Professor Ben Wang. Multiparametric MRI can characterize clot composition (e.g., T1 mapping, diffusion‑weighted imaging) to predict lytic susceptibility, while high‑frame‑rate ultrasound velocity vector imaging captures micro‑recirculation zones. In one robotic demonstration, Doppler ultrasound tracked the rotation of a helical microrobot and automatically adjusted the magnetic field to navigate against blood flow in a branched vascular model – all while B‑mode imaging monitored thrombolysis progress.
"The future is not a competition between tethered and untethered – it is synergy," concludes Professor Qinglong Wang. A tethered catheter will provide proximal access, energy delivery and procedural safety, while untethered micro/nanoagents perform distal intervention and microenvironment modulation. Artificial intelligence‑assisted control and image‑driven feedback will enable adaptive, patient‑specific thrombolysis. However, key barriers remain: robust navigation under complex hemodynamics, clear post‑treatment clearance routes (active retrieval, biodegradation or renal elimination), standardized safety windows for field‑assisted interventions, and seamless integration into existing interventional workflows. Addressing these challenges will turn proof‑of‑concept micro/nanorobots into clinically deployable platforms.
"By bridging two complementary technology paths under unified imaging guidance, we can achieve faster, more complete and safer recanalization – from large vessels down to the microcirculation," says Professor Ben Wang. "This review provides an actionable roadmap for researchers and clinicians to accelerate translation."
Authors of the paper include Jiajun He, Zhixin Xia, Lipeng Liao, Xu Li, Xuhao Wu, Jie Shen, Qinglong Wang, and Ben Wang.
This work was supported by the National Natural Science Foundation of China (grant number 52475308), the Shenzhen Medical Research Fund (SMRF) (A2303074), the Guangdong Basic and Applied Basic Research Foundation (2026B1515020076 and 2025A1515012211), and the Shanghai Key Laboratory of Flexible Medical Robotics (grant no. SKLFMR-101).
The paper "Micro/Nanorobotic Systems for Imaging-Guided Closed-Loop Thrombus Recanalization" was published in the journal Cyborg and Bionic Systems on Jun. 5, 2026, at DOI: 10.34133/cbsystems.0592.
