Targeted thrombolysis by magnetoacoustic particles in photothrombotic stroke model

Abstract

Background Recombinant tissue plasminogen activator (rtPA) has a short half-life, and additional hemorrhagic transformation (HT) can occur when treatment is delayed. Here, we report the design and thrombolytic performance of 3 $$\upmu$$ μ m discoidal polymeric particles loaded with rtPA and superparamagnetic iron oxide nanoparticles (SPIONs), referred to as rmDPPs, to address the HT issues of rtPA. Methods The rmDPPs consisted of a biodegradable polymeric matrix, rtPA, and SPIONs and were synthesized via a top-down fabrication. Results The rmDPPs could be concentrated at the target site with magnetic attraction, and then the rtPA could be released under acoustic stimulus. Therefore, we named that the particles had magnetoacoustic properties. For the in vitro blood clot lysis, the rmDPPs with magnetoacoustic stimuli could not enhance the lytic potential compared to the rmDPPs without stimulation. Furthermore, although the reduction of the infarcts in vivo was observed along with the magnetoacoustic stimuli in the rmDPPs, more enhancement was not achieved in comparison with the rtPA. A notable advantage of rmDPPs was shown in delayed administration of rmDPPs at poststroke. The late treatment of rmDPPs with magnetoacoustic stimuli could reduce the infarcts and lead to no additional HT issues, while rtPA alone could not show any favorable prognosis. Conclusion The rmDPPs may be advantageous in delayed treatment of thrombotic patients.

Transcranial Magneto-Acoustic Stimulation Protects Synaptic Rehabilitation from Amyloid-Beta Plaques via Regulation of Microglial Functions

“…Magnetic-acoustic nanoparticles are targeted using magnetic fields, and drug delivery is facilitated through the application of ultrasounds [60][61][62]. It is important to note that the static magnetic field and ultrasounds are utilized independently, without any overlap or integration.…”

Polymeric nanocarriers delivery systems in ischemic stroke for targeted therapeutic strategies

“…Typically, these nanoparticles are part of a drug delivery system, which is formed by emulsifying polymeric materials. This includes polymers like polyethylene glycol (PEG) [ 71 – 76 ], polylactic acid (PLA), and polylactic-co-glycolic acid (PLGA) [ 77 – 81 ]. These systems act as self-catalytic regulators of the BBB via internal encapsulation mechanisms.…”

“…Meanwhile, the biodegradable nature of PLGA allowed the slow release of rtPA in the target area, effectively reducing the therapeutic dose of rtPA and lowering the risk of bleeding. What’s more, Cui et al prepared PLGA loaded with rtPA and superparamagnetic iron oxide nanoparticles (SPIONs) (rmDPPs) using a top-down approach [ 81 ]. Specifically, they used semi-permanent polydimethylsiloxane (PDMS) molds as master templates to synthesize and mold disposable polyvinyl alcohol (PVA) films, which were then collected by filtration and purification to obtain rmDPPs (Fig.…”

Advances in smart delivery of magnetic field-targeted drugs in cardiovascular diseases

“…In 2022, a complete study was presented by Choi et al. [ 89 ]. They synthesized SPIONs by pyrolysis and assembled poly(lactic-co-glycolic acid) (PLGA), rtPA, and SPIONs into disc-shaped particles with a diameter of approximately 3 μm using a top-down approach.…”

“…More importantly, they did not produce any hemorrhagic transformation after thrombolysis, the safety was good, and the mouse models obtained the recovery of motor function. However, the efficacy of this magnetoacoustic device did not differ much from that of rtPA alone, which may be its limitation [ 89 ]. Nevertheless, all three experiments provided encouraging results demonstrating the potential of magnetic targeting for thrombolytic therapy of ischemic stroke.…”