충북대 / 이정훈, 이동원*
Abstract
A blood clot (thrombus) is formed as a final product of the hemostatic process with two major components, a mesh of cross-linked fibrin and platelets activated by high concentration of hydrogen peroxide (H2O2). Thrombus formation impedes blood flow to brain and heart and is a principle cause of life-threatening diseases such as stroke and myocardial infarction. Aspirin has been widely used for the treatment and prevention of various cardiovascular diseases, but is unable to target a thrombus and scavenge a high level of H2O2. In this study, we report thrombus targeting aspirin polyconjugate particles (T-APP) as a near infrared imaging agent and on-demand therapeutic agent for thrombotic vascular diseases. T-APP were formulated from H2O2-activatable aspirin polyconjugate, fibrin-specific peptides and fluorescent IR780. In mouse models of tail bleeding and arterial thrombosis, T-APP targeted the thrombosed vessels rapidly with excellent specificity. T-APP also exerted highly strong antithrombotic activity in the thrombosed vessel by suppressing anti-inflammatory cytokines and inhibiting platelet activation. Based on the unique features such as specific thrombus targeting, H2O2 scavenging, and on-demand therapeutic actions, the rationally engineered T-APP have important ramifications on imaging and on-demand therapy of thrombotic disorders.
Author information
Lee J1, Jeong L1, Jung E1, Ko C1, Seon S1, Noh J2, Lee D3.
1
Department of BIN Convergence Technology, Chonbuk National University, Baekjedaero 567, Jeonju, Chonbuk 54896, Republic of Korea.
2
Department of Polymer·Nano Science and Technology, Chonbuk National University, Baekjedaero 567, Jeonju, Chonbuk 54896, Republic of Korea.
3
Department of BIN Convergence Technology, Chonbuk National University, Baekjedaero 567, Jeonju, Chonbuk 54896, Republic of Korea; Department of Polymer·Nano Science and Technology, Chonbuk National University, Baekjedaero 567, Jeonju, Chonbuk 54896, Republic of Korea. Electronic address: dlee@chonbuk.ac.kr.