Micro/Nanorobotic Systems for Imaging-Guided Closed-Loop Thrombus Recanalization

Figures

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  Fig. 1.. Common thrombotic occlusions in the human body and 2 major recanalization modalities: tethered endovascular intervention (right) and untethered micro/nanoagent-based therapy (left). Figure created with BioRender.com.

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  Fig. 2.. Comparison of conventional tethered thrombectomy modalities and representative next-generation tethered mechanical approaches. (A) The CANADAPT catheter removes thrombi via aspiration driven by externally applied negative pressure, typically relying on catheter lumen size and sustained suction to extract clot material [36]. (B) Schematic of stent retriever thrombectomy: the stent is deployed across the thrombus, embeds within the clot network, and is subsequently retrieved to remove the clot en bloc; performance can depend on clot composition/adhesion and may be associated with clot fragmentation. Figure created with BioRender.com. In contrast to these conventional mechanical strategies (A and B), which primarily rely on bulk extraction by suction and/or traction, (C and D) depict next-generation mechanical thrombectomy concepts that emphasize controlled local mechanical loading and actuation. (C) Millimeter-scale rotational thrombectomy, where coupled compressive and shear loading compacts the loose fibrin network, thereby reducing thrombus volume and facilitating removal [6]. (D) Operating principle of a magnetically actuated microcatheter system, enabling controlled distal…

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  Fig. 3.. Representative drug-carrier platforms for thrombolysis. Schematic overview of major carrier classes (e.g., lipid-, polymer-, hydrogel-, inorganic-, biomimetic-, and bubble-based systems) developed to improve thrombolytic drug delivery and clot dissolution. In general, these platforms aim to enhance local accumulation at thrombi, prolong circulation, and enable controlled or stimuli-responsive release to reduce systemic exposure and bleeding risk. Each carrier class offers distinct strengths while also presenting trade-offs (e.g., loading/protection, release controllability, targeting/field responsiveness, biocompatibility and safety, and in vivo stability); therefore, only a high-level summary is provided here without detailed discussion. Figure created with BioRender.com.

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  Fig. 4.. Untethered combinatorial strategies for thrombolytic therapy. Schematic summary of 4 representative mechanisms that enhance thrombolysis via external fields or autonomous motion: magnetic field-guided targeting and mechanical agitation (A), optical/near-infrared (NIR) photothermal heating to accelerate clot microstructural loosening and drug penetration (B), acoustic (ultrasound) enhancement for localization, triggered release, and improved intraclotal transport (C), and self-propelled chemical/micromotor action enabling active penetration and thrombus-directed accumulation (D). (A) Heparinoid polymer brush-grafted magnetic nanorobots (HPB-NRs) based on MB@PSS nanoparticles, highlighting biosafety, drug-loading capacity, and magnetically targeted thrombolysis [80]. (B) Photothermal-assisted thrombolysis enabled by fucoidan/S-nitrosoglutathione/melanin@microcapsules (FGM@MCs) under NIR irradiation [81]. (C) Precision delivery combining magnetic localization with ultrasound-triggered tPA release from magnetic microbubbles coated with SiO2 and loaded with tPA (MMB–SiO2–tPA) [71]. (D) Self-propelled targeted thrombolysis mediated by GOx-powered Janus platelet nanoparticles (GPNP–PAs)…

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  Fig. 5.. Imaging-driven closed-loop framework for thrombosis intervention. Imaging supports (i) thrombus localization and risk assessment [87], (ii) navigation of therapeutic devices or micro/nanoagents [88], and (iii) real-time therapy monitoring with feedback-regulated control [89].

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  Fig. 6.. Closed-loop thrombus characterization, registration, and autonomous navigation framework. (A) Pre-lysis multi-sequence thrombus imaging (MSTI) combining T1 mapping, diffusion-weighted imaging/apparent diffusion coefficient (DWI/ADC), and magnetization transfer imaging to quantify thrombus composition and estimate lysis probability [87]. (B) Multimodal MRI–ultrasound registration aligns preoperative 3D vessel geometry with intraoperative 2D ultrasound through iterative spatial optimization, enabling accurate localization [88]. (C) A mobile actuation platform (hybrid torque–force control to counter blood flow) co-moves with a mobile ultrasound probe for real-time Doppler tracking, supporting closed-loop localization and autonomous navigation during thrombus intervention [89].