Synergistic Integration and Pharmacomechanical Function of Enzyme-Magnetite Nanoparticle Swarms for Low-Dose Fast Thrombolysis

Autor: Xiuzhen Tang, Laliphat Manamanchaiyaporn, Qi Zhou, Chenyang Huang, Lihuang Li, Ziqiao Li, Longchen Wang, Jienan Wang, Lei Ren, Tiantian Xu, Xiaohui Yan, Yuanyi Zheng
Rok vydání: 2022
Předmět:
Zdroj: Tang, X, Manamanchaiyaporn, L, Zhou, Q, Huang, C, Li, L, Li, Z, Wang, L, Wang, J, Ren, L, Xu, T, Yan, X & Zheng, Y 2022, ' Synergistic Integration and Pharmacomechanical Function of Enzyme-Magnetite Nanoparticle Swarms for Low-Dose Fast Thrombolysis ', Small, vol. 18, no. 34, 2202848 . https://doi.org/10.1002/smll.202202848
ISSN: 1613-6829
DOI: 10.1002/smll.202202848
Popis: Magnetic micro-/nanoparticles are extensively explored over the past decade as active diagnostic/therapeutic agents for minimally invasive medicine. However, sufficient function integration on these miniaturized bodies toward practical applications remains challenging. This work proposes a synergistic strategy via integrating particle functionalization and bioinspired swarming, demonstrated by recombinant tissue plasminogen activator modified magnetite nanoparticles (rtPA-Fe3O4 NPs) for fast thrombolysis in vivo with low drug dosage. The synthesized rtPA-Fe3O4 NPs exhibit superior magnetic performance, high biocompatibility, and thrombolytic enzyme activity. Benefiting from a customized magnetic operation system designed for animal experiments and preclinical development, these agglomeration-free NPs can assemble into micro-/milli-scale swarms capable of robust maneuver and reconfigurable transformation for on-demand tasks in complex biofluids. Specifically, the spinning mode of the swarm exerts focused fluid shear stresses while rubbing on the thrombus surface, constituting a mechanical force for clot breakdown. The synergy of the NPs’ inherent enzymatic effect and swarming-triggered fluid forces enables amplified efficacy of thrombolysis in an in vivo occlusion model of rabbit carotid artery, using lower drug concentration than clinical dosage. Furthermore, swarming-enhanced ultrasound signals aid in imaging-guided treatment. Therefore, the pharmacomechanical NP swarms herein represent an injectable thrombolytic tool joining advantages of intravenous drug therapy and robotic intervention.
Databáze: OpenAIRE