Removing nanomachines post-treatment challenges all endovascular therapies employing injectable nanobots. A groundbreaking hybrid thrombosis treatment system from the University of Hong Kong, now in preclinical study, propels research forward.
In Los Angeles, Bionaut aims to advance its nanobots, designed for delivering medication for a genetic central nervous system disorder, from preclinical to human trials. Concurrently, in China, researchers at the University of Hong Kong’s Department of Mechanical and Automation Engineering have initiated in vivo studies to assess “retrievable nanobots,” designed to be removed after application in blood vessels for thrombolytic therapy.
This initiative, detailed in “tPA-anchored nanorobots for in vivo arterial recanalization at submillimeter-scale segments” (Science Advances, January 31, 2024), addresses an enduring challenge in the field: conducting high-precision therapy within the complex network of blood vessels. Despite their ability to navigate minute sections, the partially non-biodegradable makeup of nanobots necessitates their removal, presenting significant challenges.
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Nanobot Thrombolytic Therapy – Understanding Thrombolytic Therapy and Nanobot Support
Thrombolytic therapy targets “thrombi,” solid blood masses that obstruct blood vessels, stopping nutrient and oxygen flow to organs, leading to heart attacks, strokes, and pulmonary embolisms [source: Thrombosis: symptoms and causes – Heart Research Institute].
Treatments vary, from surgical thrombectomy to thrombolysis, using “fibrinolytic” drugs administered intravenously or via catheter directly at the thrombus site [source: Intravenous Thrombolysis for Acute Ischemic Stroke – National Library of Medicine]. Researchers highlight that catheter-based delivery offers precise drug dosing, mitigating bleeding risks inherent in thrombolysis.
Originally termed “nanomotors,” these nanobots, designed over two decades ago for targeted and confined drug delivery, provide a superior solution to catheter use alone. They navigate blood vessel obstructions, especially in small, deep segments, with sizes ranging from 0.1 to 10 micrometers and precise movement control.
“Nanobots provide a more precise approach than solely using a catheter for directly targeting obstructions in blood vessels, especially within small segments situated in deep regions. This is attributed to their diminutive size—ranging from 0.1 to 10 micrometers—and the superior control over their movement.”
Challenges of Nanobots in Blood Vessels
Recent developments in thrombolytic therapy nanobots aim to enhance movement control in blood vessels, focusing on maintaining direction, reaching targets without damaging vessel walls, precise drug release, and safe return.
Innovations include chemotaxis-driven nanobots for targeted drug transport [source: Chemotaxis-Guided Hybrid Neutrophil Micromotors for Targeted Drug Transport – National Library of Medicine] and those balancing hydrodynamic and magnetic properties for precise navigation [source: “A novel tissue culture tray for the study of magnetically induced rotation and translation of iron oxide nanoparticles” – IEEE Xplore]. A 2020 study developed a porous silica and platinum nanobot for deep thrombus drug delivery, using near-infrared light for movement [source: “Platelet-derived porous nanomotor for thrombus therapy” – ScienceAdvances], yet these remained at the in vitro phase.
Nanobots relying solely on hydrodynamics, though faster in drug release, risk dispersing medication outside the target area, potentially causing hemorrhages and thus, are deemed unsafe. This led to exploring “hybrid” methodologies for safely retrieving nanomachines post-task, distinguishing them from fully biodegradable nanoparticles that cannot navigate independently.
Retrievable Nanobot Micro-swarm for Thrombolytic Therapy
The Chinese research team has designed a thrombolytic therapy system featuring a retrievable colloidal micro-swarm of Fe3O4@mSiO2 nanobots anchored to the “tissue Plasminogen Activator” (tPA), injected directly into the target site via catheter with magnetic guidance and X-ray fluoroscopy imaging.
Fe3O4@mSiO2 denotes ferrous-ferric oxide nanostructures coated with mesoporous silica [source: Facile synthesis of core\shell Fe3O4@mSiO2(Hb) and its application for organic wastewater treatment – ScienceDirect]., blending natural colloids with magnetic ferrous-ferric oxide to enable swift, precise bloodstream navigation.
The catheter positions the swarm; then, external magnetic fields guide the tPA-nbots are released and directed towards the clot by an external magnetic field. Their collective movement is specifically initiated by rotating magnetic fields, compelling the magnetized nanobots to assemble into ‘chains.’ Once in formation, they make contact with the thrombus, triggering the thrombolysis process,” the team elucidates.
Post-therapy, the nanobots return to the catheter for removal, showcasing efficient retrieval.
Glimpses of futures
Researchers from the Department of Mechanical and Automation Engineering at the University of Hong Kong have commenced animal trials of the tPA-nbot micro-swarm for endovascular thrombolytic therapy. Provided that no significant obstacles emerge, it is anticipated that several years will be required to complete these studies successfully and possibly advance to human trials. At present, the animal testing of nanobots for drug delivery is in its early stages, advancing slowly due to the complexity and specific characteristics of the diseases being examined, which include vascular, ophthalmic, orthopedic, gastrointestinal, and oncological conditions [source: “Biosafety, functionalities, and applications of biomedical micro/nanomotors” – National Library of Medicine].
“The research group has indicated that initial tests have shown that our retrievable micro-swarm of nanobots can dissolve a thrombus in vitro (not within a living organism) in approximately twenty minutes, and ex vivo (on living tissue outside of the organism), specifically in the human placenta, in 30 minutes,” aiming to enhance these timings in further animal studies. Regarding the nanobots’ retrieval after use, the team has managed to recover 80% of tPA-nbots near the catheter, subsequently extracting them from the bloodstream. These encouraging outcomes signal potential advancements, though research must still overcome challenges related to controlling nanobot movements within blood vessels and achieving precise thrombolytic drug delivery without dispersion.
Let us now attempt to forecast future scenarios using the STEPS matrix, which enables us to outline the impacts, across various fronts, of employing the removable nanobot micro-swarm in humans for endovascular thrombolytic therapy.
S – SOCIAL: thrombolytic therapy with the injection, into the blood vessels, of a micro army of nanobots that return to the base after performing their task, just as a team of flesh-and-blood surgeons would do, would mean a less invasive, quicker and, above all, safer intervention for patients because of a more targeted dosage of scoagulants than the traditional method, resulting in a shorter recovery of their function after thrombosis.
T – TECHNOLOGY: the evolution of the method developed by the Chinese working group for the design of its nanobots – which combines an aqueous substance such as colloidal and ferrous-ferric oxide – could in the future have a positive impact on those strands of biomedical research that study the use of nanomachines within fluid, submillimetre, impervious and branched environments such as blood vessels. One thinks, for example, of the treatment of those tumour masses located in organs particularly supplied with blood such as the lungs and liver.
E – ECONOMY: in addition to the positive impact that an intervention such as the one described above would have on the duration of hospitalisation, which would become shorter, with a related reduction in costs for healthcare systems, in a future scenario in which the injection of nanobots into human blood vessels would become a recognised and official practice, it will be essential to create the figure of the biomedical engineer specialised in nanorobotics within hospitals, to support the medical staff dedicated to endovascular thrombolytic therapy.
P – POLITICAL: from a regulatory point of view, the adoption of nanobots for thrombolytic therapy on humans would raise a whole series of questions concerning their safety, both from the point of view of the materials used for their manufacture (which must be non-toxic), and with regard to the techniques for their insertion and recovery. In this regard, in a future scenario, a legislative framework regulating these aspects and a special Supervisory Commission to carry out periodic inspections of healthcare facilities where nanorobotics are practised for endovascular operations should be envisaged.
S – SUSTAINABILITY: in the future, the evolution of techniques of targeted administration of thrombolytic drug by nanobots – only where necessary, directly into the thrombus, in order to scoagulate it in situ – will increasingly avoid the risk of drug dispersion (with a positive impact on the reduction of its side effects) and, consequently, its waste. We can say, in the long run, drug dlivery applied to human thrombolytic endovascular therapywill contribute to the sustainable use of fibrinolytic drugs, with positive repercussions on the sustainability of global healthcare.
