Ferrite-encapsulated nanoparticles with stable photothermal performance for multimodal imaging-guided atherosclerotic plaque neovascularization therapy

作者全名："Yang, Zhuowen; Yao, Jianting; Wang, Jianxin; Zhang, Cong; Cao, Yang; Hao, Lan; Yang, Chao; Wu, Changjun; Zhang, Jingqi; Wang, Zhigang; Ran, Haitao; Tian, Ye"

作者地址："[Yang, Zhuowen; Zhang, Jingqi; Tian, Ye] Harbin Med Univ, Affiliated Hosp 1, Cardiovasc Inst, Dept Cardiol, Harbin 150001, Peoples R China; [Yang, Zhuowen] Harbin Med Univ, Affiliated Hosp 1, Dept Gerontol, Harbin 150001, Peoples R China; [Yao, Jianting; Cao, Yang; Hao, Lan; Wang, Zhigang; Ran, Haitao] Chongqing Med Univ, Dept Ultrasound, Chongqing Key Lab Ultrasound Mol Imaging, Affiliated Hosp 2, Chongqing 400010, Peoples R China; [Wang, Jianxin; Zhang, Cong; Wu, Changjun] Harbin Med Univ, Dept Ultrasound, Affiliated Hosp 1, Harbin 150001, Peoples R China; [Yang, Chao] Univ Chinese Acad Sci, Chongqing Gen Hosp, Dept Radiol, Chongqing 400014, Peoples R China; [Tian, Ye] Harbin Med Univ, Dept Pathophysiol, Minist Educ, Harbin 150086, Peoples R China; [Tian, Ye] Harbin Med Univ, Key Lab Cardiovasc Pathophysiol, Key Lab Cardiovasc Med Res, Minist Educ, Harbin 150086, Peoples R China"

通信作者："Tian, Y (corresponding author), Harbin Med Univ, Affiliated Hosp 1, Cardiovasc Inst, Dept Cardiol, Harbin 150001, Peoples R China.; Tian, Y (corresponding author), Harbin Med Univ, Dept Pathophysiol, Minist Educ, Harbin 150086, Peoples R China.; Tian, Y (corresponding author), Harbin Med Univ, Key Lab Cardiovasc Pathophysiol, Key Lab Cardiovasc Med Res, Minist Educ, Harbin 150086, Peoples R China."

来源：BIOMATERIALS SCIENCE

ESI学科分类：MATERIALS SCIENCE

WOS号：WOS:000672881000001

JCR分区：Q2

影响因子：6.6

年份：2021

卷号：9

期号：16

开始页：5652

结束页：5664

文献类型：Article

关键词：　

摘要："Pathological angiogenesis is a critical contributor to atherosclerotic plaque rupture. However, there are few effective theranostic strategies to stabilize plaques by suppressing neovascularization. In this study, we fabricated a polymeric nanosystem using 3 nm manganese ferrite (MnFe2O4) and perfluorohexane (PFH) stabilized by polylactic acid-glycolic acid (PLGA) shells and conjugated to the surface of an anti-vascular endothelial growth factor receptor 2 (VEGFR2) antibody [ramucirumab (Ram)]. The PFH@PLGA/MnFe2O4-Ram nanoparticles (NPs) were used as atherosclerotic plaque angiogenesis theranostics for multimodal imaging-guided photothermal therapy (PTT). Three-nanometer MnFe2O4 is an excellent magnetic resonance imaging T1 and photoacoustic imaging contrast agent. Upon exposure to near-infrared (NIR) light, MnFe2O4 in the NPs could transform NIR light into thermal energy for the photothermal elimination of plaque angiogenesis. Additionally, optical droplet vaporization of PFH in the NPs triggered by the thermal effect to form gas bubbles enhanced ultrasound imaging. Our in vitro experiments revealed that PFH@PLGA/MnFe2O4-Ram NPs actively accumulated in rabbit aortic endothelial cells, and NP-mediated PTT promoted endothelial cell apoptosis while inhibiting their proliferation, migration, and tubulogenesis. Notably, the PFH@PLGA/MnFe2O4-Ram NPs possessed excellent photostability and biocompatibility. In the rabbit advanced atherosclerotic plaque model, PFH@PLGA/MnFe2O4-Ram NP-guided PTT significantly induced apoptosis of neovascular endothelial cells and improved the hypoxia status in the plaque 3 days after treatment. On day 28, PTT significantly reduced the density of neovessels and subsequently stabilized rabbit plaques by inhibiting plaque hemorrhage and macrophage infiltration. Collectively, these results suggest that PFH@PLGA/MnFe2O4-Ram NP-guided PTT is a safe and effective theranostic strategy for inhibiting atherosclerotic plaque angiogenesis."

基金机构："National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81530052, 81727809, 82071926, 81630047]; Construction Project of Postgraduate Tutor Team in Chongqing [dstd201904]"

基金资助正文："This work was funded by the National Natural Science Foundation of China (grant no. 81530052, 81727809, 82071926 and 81630047) and the Construction Project of Postgraduate Tutor Team in Chongqing (grant no. dstd201904)."