TY - JOUR
T1 - Synergistic Integration and Pharmacomechanical Function of Enzyme-Magnetite Nanoparticle Swarms for Low-Dose Fast Thrombolysis
AU - Tang, Xiuzhen
AU - Manamanchaiyaporn, Laliphat
AU - Zhou, Qi
AU - Huang, Chenyang
AU - Li, Lihuang
AU - Li, Ziqiao
AU - Wang, Longchen
AU - Wang, Jienan
AU - Ren, Lei
AU - Xu, Tiantian
AU - Yan, Xiaohui
AU - Zheng, Yuanyi
N1 - Funding Information:
X.T., L.M., and Q.Z. contributed equally to this work. The authors thank Dr. Ying Zhang (Department of Obstetrics and Gynaecology, Wuhan University) for assisting animal experiments, and Prof. Dongxu Zhang, Mr. Fei Duan, Mr. Yanghui Chen, and Mr. Juntian Zeng (School of Public Health, Xiamen University) for offering 3D printing instruments and supporting the use of them. This project was supported by the NSFC Key Projects of International Cooperation and Exchanges (81720108023), the NSFC Key Project (82030050), the National Key R&D Program of China (2018YFC0115200), the Fundamental Research Funds for the Central Universities of China (20720190076), the Opening Project of Guangdong Provincial Key Lab of Robotics and Intelligent System (XDHT2019588A), the National Natural Science Foundation of China (82001845) and Innovative research team of high‐level local universities in Shanghai.
Funding Information:
X.T., L.M., and Q.Z. contributed equally to this work. The authors thank Dr. Ying Zhang (Department of Obstetrics and Gynaecology, Wuhan University) for assisting animal experiments, and Prof. Dongxu Zhang, Mr. Fei Duan, Mr. Yanghui Chen, and Mr. Juntian Zeng (School of Public Health, Xiamen University) for offering 3D printing instruments and supporting the use of them. This project was supported by the NSFC Key Projects of International Cooperation and Exchanges (81720108023), the NSFC Key Project (82030050), the National Key R&D Program of China (2018YFC0115200), the Fundamental Research Funds for the Central Universities of China (20720190076), the Opening Project of Guangdong Provincial Key Lab of Robotics and Intelligent System (XDHT2019588A), the National Natural Science Foundation of China (82001845) and Innovative research team of high-level local universities in Shanghai.
Publisher Copyright:
© 2022 Wiley-VCH GmbH.
PY - 2022/8/25
Y1 - 2022/8/25
N2 - 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.
AB - 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.
KW - magnetite nanoparticles
KW - enzyme
KW - magnetic manipulation
KW - swarm control
KW - shear stress
KW - thrombolysis
U2 - 10.1002/smll.202202848
DO - 10.1002/smll.202202848
M3 - Article
SN - 1613-6829
VL - 18
JO - Small
JF - Small
IS - 34
M1 - 2202848
ER -