Painting blood vessels and atherosclerotic plaques with an adhesive drug depot

被引:104
作者
Kastrup, Christian J. [1 ,4 ,5 ]
Nahrendorf, Matthias [6 ]
Figueiredo, Jose Luiz [6 ]
Lee, Haeshin [9 ]
Kambhampati, Swetha [1 ]
Lee, Timothy [1 ]
Cho, Seung-Woo [10 ]
Gorbatov, Rostic [6 ]
Iwamoto, Yoshiko [6 ]
Dang, Tram T. [1 ]
Dutta, Partha [6 ]
Yeon, Ju Hun [4 ,5 ]
Cheng, Hao [1 ,11 ]
Pritchard, Christopher D. [1 ]
Vegas, Arturo J. [1 ]
Siegel, Cory D. [6 ]
MacDougall, Samantha [1 ]
Okonkwo, Michael [1 ]
Anh Thai [1 ]
Stone, James R. [7 ,8 ]
Coury, Arthur J. [12 ]
Weissleder, Ralph [6 ]
Langer, Robert [1 ,2 ,3 ]
Anderson, Daniel G. [1 ,2 ,3 ]
机构
[1] MIT, David H Koch Inst Integrated Canc Res, Cambridge, MA 02139 USA
[2] MIT, Dept Chem Engn, Cambridge, MA 02139 USA
[3] MIT, Harvard MIT Div Hlth Sci & Technol, Cambridge, MA 02139 USA
[4] Univ British Columbia, Michael Smith Labs, Vancouver, BC V6T 1Z4, Canada
[5] Univ British Columbia, Dept Biochem & Mol Biol, Vancouver, BC V6T 1Z4, Canada
[6] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA
[7] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA
[8] Harvard Univ, Sch Med, Boston, MA 02114 USA
[9] Korea Adv Inst Sci & Technol, Dept Chem, Grad Sch Nanosci & Technol, Taejon 305701, South Korea
[10] Yonsei Univ, Dept Biotechnol, Seoul 120749, South Korea
[11] Drexel Univ, Dept Mat Sci & Engn, Philadelphia, PA 19104 USA
[12] Coury Consulting Serv, Boston, MA 02116 USA
基金
加拿大健康研究院; 美国国家卫生研究院;
关键词
biomaterials; catechol; delivery; endoluminal paving; CORONARY ATHEROSCLEROSIS; CARDIOVASCULAR-DISEASE; VULNERABLE PLAQUE; HYDROGEL BARRIERS; STENT THROMBOSIS; ALGINATE; MECHANISMS; DELIVERY; PERSPECTIVES; DEGRADATION;
D O I
10.1073/pnas.1217972110
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The treatment of diseased vasculature remains challenging, in part because of the difficulty in implanting drug-eluting devices without subjecting vessels to damaging mechanical forces. Implanting materials using adhesive forces could overcome this challenge, but materials have previously not been shown to durably adhere to intact endothelium under blood flow. Marine mussels secrete strong underwater adhesives that have been mimicked in synthetic systems. Here we develop a drug-eluting bioadhesive gel that can be locally and durably glued onto the inside surface of blood vessels. In a mouse model of atherosclerosis, inflamed plaques treated with steroid-eluting adhesive gels had reduced macrophage content and developed protective fibrous caps covering the plaque core. Treatment also lowered plasma cytokine levels and biomarkers of inflammation in the plaque. The drug-eluting devices developed here provide a general strategy for implanting therapeutics in the vasculature using adhesive forces and could potentially be used to stabilize rupture-prone plaques.
引用
收藏
页码:21444 / 21449
页数:6
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