Open AccessLow‐Intensity Focused Ultrasound‐Responsive Ferrite‐Encapsulated Nanoparticles for Atherosclerotic Plaque Neovascularization Theranostics
Author(s) -
Yao Jianting,
Yang Zhuowen,
Huang Liandi,
Yang Chao,
Wang Jianxin,
Cao Yang,
Hao Lan,
Zhang Liang,
Zhang Jingqi,
Li Pan,
Wang Zhigang,
Sun Yang,
Ran Haitao
Publication year - 2021
Publication title -
advanced science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.388
H-Index - 100
ISSN - 2198-3844
DOI - 10.1002/advs.202100850
Subject(s) - sonodynamic therapy , neovascularization , angiogenesis , plga , photodynamic therapy , cancer research , chemistry , apoptosis , reactive oxygen species , medicine , biomedical engineering , nanoparticle , nanotechnology , biochemistry , materials science , organic chemistry
Pathological angiogenesis is a crucial factor that causes atherosclerotic plaque rupture. Sinoporphyrin sodium‐mediated sonodynamic therapy (DVDMS‐SDT) induces regression of plaque neovascularization in humans without causing obvious side effects. However, a clinical noninvasive theranostic strategy for atherosclerotic plaque neovascularization is urgently needed. A nanoplatform designed for multimodality imaging‐guided SDT in plaque angiogenesis theranostics, termed PFP–HMME@PLGA/MnFe 2 O 4 –ramucirumab nanoparticles (PHPMR NPs), is fabricated. It encapsulates manganese ferrite (MnFe 2 O 4 ), hematoporphyrin monomethyl ether (HMME), and perfluoropentane (PFP) stabilized by polylactic acid‐glycolic acid (PLGA) shells and is conjugated to an anti‐VEGFR‐2 antibody. With excellent magnetic resonance imaging (MRI)/photoacoustic/ultrasound imaging ability, the distribution of PHPMR NPs in plaque can be observed in real time. Additionally, they actively accumulate in the mitochondria of rabbit aortic endothelial cells (RAECs), and the PHPMR NP‐mediated SDT promotes mitochondrial‐caspase apoptosis via the production of reactive oxygen species and inhibits the proliferation, migration, and tubulogenesis of RAECs. On day 3, PHPMR NP‐mediated SDT induces apoptosis in neovessel endothelial cells and improves hypoxia in the rabbit advanced plaque. On day 28, PHPMR NP‐mediated SDT reduces the density of neovessels, subsequently inhibiting intraplaque hemorrhage and inflammation and eventually stabilizing the plaque. Collectively, PHPMR NP‐mediated SDT presents a safe and effective theranostic strategy for inhibiting plaque angiogenesis.