The heart lacks the ability to regenerate following myocardial infarction (MI), resulting in formation of scar tissue leading to cardiac failure. Epicardial cell (ECs) are a major target for MI treatment since they activate during cardiac damage, re-express cardiac embryonic transcription factors, proliferate and contribute to tissue remodelling. TRANSOFRM will develop an efficient strategy to track ECs in-vivo to assess the mechanism and the effects of their activation. We will load multifunctional nanoparticle imaging contrast agents within nanoneedles to nanoinject them inside ECs. This will allow tracking of EC behaviour following activation using imaging methods including MRI, CT and NIR.
Chiappini C, De Rosa E, Martinez JO, Liu X, Steele J, Stevens MM, Tasciotti E. Biodegradable silicon nanoneedles delivering nucleic acids intracellularly induce localized in vivo neovascularization Nat. Mater 14, 532 (2015) https://goo.gl/8v21sO
Chiappini C, Campagnolo P, Almeida CS, Abbassi Gahdi N, Chow LW, Hanna GB, Stevens MM. Mapping local cytosolic enzymatic activity in human esophageal mucosa with porous silicon nanoneedles Adv. Mater 27, 5147 (2015) https://goo.gl/gyS4fs
Hembury M, Chiappini C, Bertazzo S, Kalber TL, Drisko GL, Ogunlade O, Walker-Samuel S, Sai Krishna K, Jumeaux C, Beard P, Kumar CSSR, Porter AE, Lythgoe MF, Boissere C, Sanchez C, Stevens MM Goldi-silica quantum rattles for multimodal imaging and therapy Proc. Natl. Acad. Sci. USA 112, 1959 (2014) http://bit.ly/1IJzJiN?
Stuckey DJ, Carr CA, Martin-Rendon E, Tyler DJ, Willmott C, Cassidy PJ, Hale SJ, Schneider JE, Tatton L, Harding SE, Radda GK, Watt S, Clarke K. Iron particles for noninvasive monitoring of bone marrow stromal cell engraftment into, and isolation of viable engrafted donor cells from, the heart. Stem Cells 24, 1968 (2006) http://bit.ly/1TznggI
Stuckey DJ, McSweeney SJ, Thin MZ, Habib J, Price AN, Fiedler LR, Gsell W, Prasad SK, Schneider MD. T. mapping detects pharmacological retardation of diffuse cardiac fibrosis in mouse pressure-overload hypertrophy. Circulation Cardiovascular Imaging 7,240 (2014) http://bit.ly/1UMowT1