PMID- 34259244 OWN - NLM STAT- MEDLINE DCOM- 20210811 LR - 20210811 IS - 2047-4849 (Electronic) IS - 2047-4830 (Linking) VI - 9 IP - 16 DP - 2021 Aug 21 TI - Ferrite-encapsulated nanoparticles with stable photothermal performance for multimodal imaging-guided atherosclerotic plaque neovascularization therapy. PG - 5652-5664 LID - 10.1039/d1bm00343g [doi] AB - 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 (MnFe(2)O(4)) 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/MnFe(2)O(4)-Ram nanoparticles (NPs) were used as atherosclerotic plaque angiogenesis theranostics for multimodal imaging-guided photothermal therapy (PTT). Three-nanometer MnFe(2)O(4) is an excellent magnetic resonance imaging T1 and photoacoustic imaging contrast agent. Upon exposure to near-infrared (NIR) light, MnFe(2)O(4) 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/MnFe(2)O(4)-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/MnFe(2)O(4)-Ram NPs possessed excellent photostability and biocompatibility. In the rabbit advanced atherosclerotic plaque model, PFH@PLGA/MnFe(2)O(4)-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/MnFe(2)O(4)-Ram NP-guided PTT is a safe and effective theranostic strategy for inhibiting atherosclerotic plaque angiogenesis. FAU - Yang, Zhuowen AU - Yang Z AD - Department of Cardiology, The First Affiliated Hospital, Cardiovascular Institute, Harbin Medical University, Harbin 150001, P. R. China. yetian6@163.com yetian@ems.hrbmu.edu.cn and Department of Gerontology, The First Affiliated Hospital, Harbin Medical University, Harbin 150001, P. R. China. FAU - Yao, Jianting AU - Yao J AD - Department of Ultrasound, Chongqing Key Laboratory of Ultrasound Molecular Imaging, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, P. R. China. FAU - Wang, Jianxin AU - Wang J AD - Department of Ultrasound, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, P. R. China. FAU - Zhang, Cong AU - Zhang C AD - Department of Ultrasound, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, P. R. China. FAU - Cao, Yang AU - Cao Y AD - Department of Ultrasound, Chongqing Key Laboratory of Ultrasound Molecular Imaging, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, P. R. China. FAU - Hao, Lan AU - Hao L AUID- ORCID: 0000-0003-3720-9679 AD - Department of Ultrasound, Chongqing Key Laboratory of Ultrasound Molecular Imaging, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, P. R. China. FAU - Yang, Chao AU - Yang C AD - Department of Radiology, Chongqing General Hospital, University of Chinese Academy of Sciences, Chongqing 400014, P. R. China. FAU - Wu, Changjun AU - Wu C AD - Department of Ultrasound, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, P. R. China. FAU - Zhang, Jingqi AU - Zhang J AD - Department of Cardiology, The First Affiliated Hospital, Cardiovascular Institute, Harbin Medical University, Harbin 150001, P. R. China. yetian6@163.com yetian@ems.hrbmu.edu.cn. FAU - Wang, Zhigang AU - Wang Z AUID- ORCID: 0000-0003-4149-0862 AD - Department of Ultrasound, Chongqing Key Laboratory of Ultrasound Molecular Imaging, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, P. R. China. FAU - Ran, Haitao AU - Ran H AD - Department of Ultrasound, Chongqing Key Laboratory of Ultrasound Molecular Imaging, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, P. R. China. FAU - Tian, Ye AU - Tian Y AUID- ORCID: 0000-0003-3726-7270 AD - Department of Cardiology, The First Affiliated Hospital, Cardiovascular Institute, Harbin Medical University, Harbin 150001, P. R. China. yetian6@163.com yetian@ems.hrbmu.edu.cn and Department of Pathophysiology and Key Laboratory of Cardiovascular Pathophysiology, Harbin Medical University, Key Laboratory of Cardiovascular Medicine Research (Harbin Medical University), Ministry of Education, Harbin 150086, P. R. China. LA - eng PT - Journal Article DEP - 20210713 PL - England TA - Biomater Sci JT - Biomaterials science JID - 101593571 RN - 0 (Ferric Compounds) RN - 1317-54-0 (ferrite) SB - IM MH - Animals MH - Cell Line, Tumor MH - Endothelial Cells MH - Ferric Compounds MH - Multimodal Imaging MH - *Nanoparticles MH - Neovascularization, Pathologic/diagnostic imaging/drug therapy MH - Phototherapy MH - *Plaque, Atherosclerotic/diagnostic imaging MH - Rabbits MH - Theranostic Nanomedicine EDAT- 2021/07/15 06:00 MHDA- 2021/08/12 06:00 CRDT- 2021/07/14 08:47 PHST- 2021/07/15 06:00 [pubmed] PHST- 2021/08/12 06:00 [medline] PHST- 2021/07/14 08:47 [entrez] AID - 10.1039/d1bm00343g [doi] PST - ppublish SO - Biomater Sci. 2021 Aug 21;9(16):5652-5664. doi: 10.1039/d1bm00343g. Epub 2021 Jul 13.