In Vivo Targeting and Imaging of Atherosclerosis Using Multifunctional Virus-Like Particles of Simian Virus 40.
Atherosclerosis is a leading cause of death globally. Targeted imaging and therapeutics are desirable for the detection and treatment of the disease. In this study, we developed trifunctional Simian virus 40 (SV40)-based nanoparticles for in vivo targeting and imaging of atherosclerotic plaques. These novel trifunctional SV40-based nanoparticles encapsulate near-infrared quantum dots and bear a targeting element and a drug component. Using trifunctional SV40-based nanoparticles, we were able to noninvasively fluorescently image atherosclerotic plaques in live intact ApoE(-/-) mice. Near-infrared quantum dots encapsulated in the SV40 virus-like particles showed prominent optical properties for in vivo imaging. When different targeting peptides for vascular cell adhesion molecule-1, macrophages, and fibrin were used, early, developmental, and late stages of atherosclerosis could be targeted and imaged in live intact ApoE(-/-) mice, respectively. Targeted SV40 virus-like particles also delivered an increased concentration of the anticoagulant drug Hirulog to atherosclerosis plaques. Our study provides novel SV40-based nanoparticles with multivalency and multifunctionality suitable for in vivo imaging, molecular targeting, and drug delivery in atherosclerosis.
State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences , Wuhan 430071, China.|Graduate University of Chinese Academy of Sciences , Beijing 100049, China.|College of Life Science, Jiang Han University , Wuhan 430056, China.
Xianxun
X
Sun
State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences , Wuhan 430071, China.
Wei
W
Li
State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences , Wuhan 430071, China.
Xiaowei
X
Zhang
State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences , Wuhan 430071, China.|Graduate University of Chinese Academy of Sciences , Beijing 100049, China.
Mi
M
Qi
State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences , Wuhan 430071, China.
Zhiping
Z
Zhang
National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences , Beijing 100101, China.
Xian-En
XE
Zhang
State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences , Wuhan 430071, China.
Zongqiang
Z
Cui
D000818:Animals; D050197:Atherosclerosis / Q000000981:diagnostic imaging / Q000188:drug therapy*; D016503:Drug Delivery Systems; D006629:Hirudins / Q000008:administration & dosage*; D051379:Mice; D000074085:Mice, Knockout, ApoE; D053758:Nanoparticles; D010446:Peptide Fragments / Q000008:administration & dosage*; D058226:Plaque, Atherosclerotic / Q000000981:diagnostic imaging*; D045663:Quantum Dots; D011994:Recombinant Proteins / Q000008:administration & dosage; D013539:Simian virus 40
D006629:Hirudins; D010446:Peptide Fragments; D011994:Recombinant Proteins; C074619:bivalirudin
Hirulog; SV40 multifunctional nanoparticle; atherosclerosis; in vivo targeted imaging; quantum dots