Guiding Drug Through Interrupted Bloodstream for Potentiated Thrombolysis by C‐Shaped Magnetic Actuation System In Vivo

Abstract

Fast and effective thrombolysis using tissue plasminogen activator (tPA) is limited by the poor delivery efficiency of thrombolytic drugs, which is induced by an interrupted bloodstream and delayed recanalization. Existing magnetic micro/nanodrug‐loaded robots used for targeted thrombotic therapy are limited by the complexity of the clinical verification of nanodrugs and the limited space of magnetic actuation systems. Herein, a general drug delivery strategy based on mass transportation theory for thrombolysis is presented, and an open space C‐shaped magnetic actuation system with laser location and ultrasound imaging navigation for in vivo evaluation is developed. tPA can be guided through an interrupted bloodstream to the thrombi by the locomotion of magnetic nanoparticle swarms (MNSs), thereby improving the thrombolysis efficacy. Notably, this strategy is able to quickly establish a life channel to achieve time‐critical recanalization, which is typically inaccessible using native tPA. Both in vitro and in vivo thrombolysis experiments demonstrate that the thrombus lysis efficacy significantly increases after the application of the MNS under a rotating magnetic field. This study provides an anticipated C‐shaped magnetic actuation system for in vivo validation and also presents a clinically feasible drug delivery strategy for targeted thrombolytic therapy with minimal systemic tPA exposure.

Real-Time Ultrasound Doppler Tracking and Autonomous Navigation of a Miniature Helical Robot for Accelerating Thrombolysis in Dynamic Blood Flow

“…Untethered small-scale robots capable of navigating through intricate spaces are promising candidates for minimally invasive surgery, imaging-guided delivery, sensing, and targeted therapy applications in a living body. − Actuated by various power sources (e.g., self-propulsion, , external fields, − or hybrid actuation , ), small-scale robots embedded with controllable motion and steerability offer the capability of performing tasks in complex media (e.g., vitreous humor, gastrointestinal tract) and hard-to-reach regions (e.g., blood vessels, bile duct). − The application of small-scale robots shows potential in improving medical procedures with targeting capability, such as active delivery, − thrombolysis, − and penetration of biological barriers . Although different actuation strategies and improvements have been proposed, the controllability of small-scale robots is limited in stagnant or low-flow-rate fluidic environments.…”

Guanidinium‐Decorated Nanostructure for Precision Sonodynamic‐Catalytic Therapy of MRSA‐Infected Osteomyelitis

“…[15] However, relying on pre-existing pathological conditions, passively endogenoustriggered strategies are limited by large heterogeneity at the infection site and individual variation. [16] Exogenous triggers such as light, [17] microwave, [18] electromagnetic radiation, [19] and ultrasound (US) [20] act as remote spatiotemporal controllers of therapeutic agents irrespective of pathological characteristics. Among them, US is advantageous owning to its superior tissue penetrability and safety of mechanical waves; moreover, US has great potential for treating deep-seated bone infections without obstruction.…”

Recent Advances in Targeted Nanotherapies for Ischemic Stroke

“…Magnetic Responsive Nanosystems. Targeted drug delivery by magnetic up-conversion NPs has shown great potential 57,58 and are generated through the encapsulation of rtPA in magnetic porous materials or coating of a surface with magnetic NPs. 59 Fe 3 O 4 has been widely applied due to its high degree of biodegradability and biosafety.…”