title: Organic Semiconducting Nanoparticles as Efficient Photoacoustic Agents for Lightening Early Thrombus and Monitoring Thrombolysis in Living Mice.
abstract: Acute venous thrombosis is prevalent and potentially fatal. Accurate diagnosis of early thrombus is needed for patients in timely clinical intervention to prevent life-threatening conditions. Photoacoustic imaging (PAI) with excellent spatial resolution and high optical contrast shows more promise for this purpose. However, its application is dramatically limited by its signal-off effect on thrombus because of the ischemia in thrombus which lacks the endogenous photoacoustic (PA) signal of hemoglobin. To address this dilemma, we herein report the feasibility of using organic semiconducting nanoparticles (NPs) for contrast-enhanced PAI of thrombus in living mice. An organic semiconducting NP, self-assembled by amphiphilic perylene-3,4,9,10-tetracarboxylic diimide (PDI) molecules, is chemically modified with cyclic Arg-Gly-Asp (cRGD) peptides as a PA contrast agent (cRGD-PDI NPs) for selectively lightening early thrombus. cRGD-PDI NPs presents high PA intensity, good stability in light and serum, and sufficient blood-circulating half-life. In living mice, PA intensity of early thrombus significantly increases after tail vein injection of cRGD-PDI NPs, which is 4-fold greater than that of the control, blocking, and old thrombus groups. Pathological and immunohistochemical findings show that glycoprotein IIb/IIIa abundant in early thrombus is a good biomarker targeted by cRGD-PDI NPs for distinguishing early thrombus from old thrombus by PAI. Such a lightening PAI effect by cRGD-PDI NPs successfully provides accurate information including the profile, size and conformation, and spatial distribution of early thrombus, which may timely monitor the obstructive degree of thrombus in blood vessels and the thrombolysis effect.
authors.affiliation: Department of Orthopedics, Zhongnan Hospital of Wuhan University , Wuhan, Hubei 430071, China.
authors.forename: Cao
authors.initials: C
authors.lastname: Cui
authors.affiliation: Key Laboratory for Organic Electronics and Information Displays & Institute of Advanced Materials (IAM), Jiangsu National Synergetic Innovation Center for Advanced Materials (SICAM), Nanjing University of Posts & Telecommunications , Nanjing 210023, China.
authors.forename: Zhen
authors.identifier: 0000-0003-4056-0347
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Department of Orthopedics, Zhongnan Hospital of Wuhan University , Wuhan, Hubei 430071, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Hu
authors.affiliation: Key Laboratory for Organic Electronics and Information Displays & Institute of Advanced Materials (IAM), Jiangsu National Synergetic Innovation Center for Advanced Materials (SICAM), Nanjing University of Posts & Telecommunications , Nanjing 210023, China.
authors.forename: Jinjun
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Orthopedics, Zhongnan Hospital of Wuhan University , Wuhan, Hubei 430071, China.
authors.forename: Kangquan
authors.initials: K
authors.lastname: Shou
authors.affiliation: Key Laboratory for Organic Electronics and Information Displays & Institute of Advanced Materials (IAM), Jiangsu National Synergetic Innovation Center for Advanced Materials (SICAM), Nanjing University of Posts & Telecommunications , Nanjing 210023, China.
authors.forename: Hengheng
authors.initials: H
authors.lastname: Ma
authors.affiliation: Department of Orthopedics, Zhongnan Hospital of Wuhan University , Wuhan, Hubei 430071, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Jian
authors.affiliation: Department of Orthopedics, Zhongnan Hospital of Wuhan University , Wuhan, Hubei 430071, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Orthopedics, Zhongnan Hospital of Wuhan University , Wuhan, Hubei 430071, China.
authors.forename: Baiwen
authors.initials: B
authors.lastname: Qi
authors.affiliation: Key Laboratory for Organic Electronics and Information Displays & Institute of Advanced Materials (IAM), Jiangsu National Synergetic Innovation Center for Advanced Materials (SICAM), Nanjing University of Posts & Telecommunications , Nanjing 210023, China.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Hu
authors.affiliation: Department of Orthopedics, Zhongnan Hospital of Wuhan University , Wuhan, Hubei 430071, China.
authors.forename: Aixi
authors.initials: A
authors.lastname: Yu
authors.affiliation: Key Laboratory for Organic Electronics and Information Displays & Institute of Advanced Materials (IAM), Jiangsu National Synergetic Innovation Center for Advanced Materials (SICAM), Nanjing University of Posts & Telecommunications , Nanjing 210023, China.
authors.forename: Quli
authors.identifier: 0000-0002-9387-0165
authors.initials: Q
authors.lastname: Fan
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003287:Contrast Media / Q000737:chemistry*; D007094:Imides / Q000737:chemistry*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D041681:NIH 3T3 Cells; D053758:Nanoparticles / Q000737:chemistry*; D009842:Oligopeptides / Q000737:chemistry; D061848:Optical Imaging; D010316:Particle Size; D010569:Perylene / Q000031:analogs & derivatives* / Q000737:chemistry; D061088:Photoacoustic Techniques; D012666:Semiconductors; D013499:Surface Properties; D013501:Surface-Active Agents / Q000737:chemistry; D013927:Thrombosis / Q000000981:diagnostic imaging*; D020246:Venous Thrombosis / Q000000981:diagnostic imaging*
chemical_list: D003287:Contrast Media; D007094:Imides; D009842:Oligopeptides; D013501:Surface-Active Agents; C000716299:perylene-3,4,9,10-tetracarboxylic diimide; D010569:Perylene; C047981:arginyl-glycyl-aspartic acid
keywords: NIR absorption; PDI nanoparticles; contrast agent; early thrombus; photoacoustic imaging