Self-degrading, MRI-detectable hydrogel sensors with picomolar target sensitivity
Jason Colomb
School of Biological and Health Systems Engineering, Arizona State University, Tempe, Arizona, USA
Search for more papers by this authorKatherine Louie
School of Biological and Health Systems Engineering, Arizona State University, Tempe, Arizona, USA
Search for more papers by this authorStephen P. Massia
School of Biological and Health Systems Engineering, Arizona State University, Tempe, Arizona, USA
Search for more papers by this authorCorresponding Author
Kevin M. Bennett
School of Biological and Health Systems Engineering, Arizona State University, Tempe, Arizona, USA
School of Biological and Health Systems Engineering, Arizona State University, Tempe, Arizona===Search for more papers by this authorJason Colomb
School of Biological and Health Systems Engineering, Arizona State University, Tempe, Arizona, USA
Search for more papers by this authorKatherine Louie
School of Biological and Health Systems Engineering, Arizona State University, Tempe, Arizona, USA
Search for more papers by this authorStephen P. Massia
School of Biological and Health Systems Engineering, Arizona State University, Tempe, Arizona, USA
Search for more papers by this authorCorresponding Author
Kevin M. Bennett
School of Biological and Health Systems Engineering, Arizona State University, Tempe, Arizona, USA
School of Biological and Health Systems Engineering, Arizona State University, Tempe, Arizona===Search for more papers by this authorAbstract
Nanostructured hydrogels have been developed as synthetic tissues and scaffolds for cell and drug delivery, and as guides for tissue regeneration. A fundamental problem in the development of synthetic hydrogels is that implanted gel structure is difficult to monitor noninvasively. This work demonstrates that the aggregation of magnetic nanoparticles, attached to specific macromolecules in biological and synthetic hydrogels, can be controlled to detect changes in gel macromolecular structure with MRI. It is further shown that the gels can be made to self-degrade when they come into contact with a target molecule in as low as pM concentrations. The sensitivity of the gels to the target is finely controlled using an embedded zymogen cascade amplifier. These “MRI reporter gels” may serve as smart, responsive polymer implants, as tissue scaffolds to deliver drugs, or to detect specific pathogens in vivo. Magn Reson Med, 2010. © 2010 Wiley-Liss, Inc.
REFERENCES
- 1 Daley WP, Peters SB, Larsen M. Extracellular matrix dynamics in development and regenerative medicine. J Cell Sci 2008; 121 ( pt 3): 255–264.
- 2 Schindler M, Nur EKA, Ahmed I, Kamal J, Liu HY, Amor N, Ponery AS, Crockett DP, Grafe TH, Chung HY, Weik T, Jones E, Meiners S. Living in three dimensions: 3D nanostructured environments for cell culture and regenerative medicine. Cell Biochem Biophys 2006; 45: 215–227.
- 3 Piston DW. The coming of age of two-photon excitation imaging for intravital microscopy. Adv Drug Deliv Rev 2006; 58: 770–772.
- 4 Constantin G. Visualization and analysis of adhesive events in brain microvessels by using intravital microscopy. Methods Mol Biol 2004; 239: 189–198.
- 5 Pilatus U, Ackerstaff E, Artemov D, Mori N, Gillies RJ, Bhujwalla ZM. Imaging prostate cancer invasion with multi-nuclear magnetic resonance methods: the Metabolic Boyden Chamber. Neoplasia 2000; 2: 273–279.
- 6 Gore JC, Brown MS, Zhong J, Mueller KF, Good W. NMR relaxation of water in hydrogel polymers: a model for tissue. Magn Reson Med 1989; 9: 325–332.
- 7 Bull SR, Guler MO, Bras RE, Meade TJ, Stupp SI. Self-assembled peptide amphiphile nanofibers conjugated to MRI contrast agents. Nano Lett 2005; 5: 1–4.
- 8 Bulte JW, Douglas T, Mann S, Frankel RB, Moskowitz BM, Brooks RA, Baumgarner CD, Vymazal J, Frank JA. Magnetoferritin. Biomineralization as a novel molecular approach in the design of iron-oxide-based magnetic resonance contrast agents. Invest Radiol 1994; 29 ( Suppl 2): S214–S216.
- 9 Laurent S, Forge D, Port M, Roch A, Robic C, Vander Elst L, Muller R. Magnetic iron oxide nanoparticles: synthesis, stabilization, vectorization, physicochemical charicterizations, and biological applications. Chem Rev 2008; 108: 2064–2110.
- 10 Atanasijevic T, Shusteff M, Fam P, Jasanoff A. Calcium-sensitive MRI contrast agents based on superparamagnetic iron oxide nanoparticles and calmodulin. Proc Natl Acad Sci USA 2006; 103: 14707–14712.
- 11 Bennett KM, Zhou H, Sumner JP, Dodd SJ, Bouraoud N, Doi K, Star RA, Koretsky AP. MRI of the basement membrane using charged nanoparticles as contrast agents. Magn Reson Med 2008; 60: 564–574.
- 12 Uchida M, Flenniken ML, Allen M, Willits DA, Crowley BE, Brumfield S, Willis AF, Jackiw L, Jutila M, Young MJ, Douglas T. Targeting of cancer cells with ferrimagnetic ferritin cage nanoparticles. J Am Chem Soc 2006; 128: 16626–16633.
- 13 Bulte JW, Douglas T, Mann S, Frankel RB, Moskowitz BM, Brooks RA, Baumgarner CD, Vymazal J, Strub MP, Frank JA. Magnetoferritin: characterization of a novel superparamagnetic MR contrast agent. J Magn Reson Imaging 1994; 4: 497–505.
- 14 Bulte JW, Douglas T, Mann S, Vymazal J, Laughlin PG, Frank JA. Initial assessment of magnetoferritin biokinetics and proton relaxation enhancement in rats. Acad Radiol 1995; 2: 871–878.
- 15 Wunderbaldinger P, Josephson L, Weissleder R. Crosslinked iron oxides (CLIO): a new platform for the development of targeted MR contrast agents. Acad Radiol 2002; 9 ( Suppl 2): S304–S306.
- 16 Zhao M, Josephson L, Tang Y, Weissleder R. Magnetic sensors for protease assays. Angew Chem Int Ed Engl 2003; 42: 1375–1378.
- 17 Bennett KM, Shapiro EM, Sotak CH, Koretsky AP. Controlled aggregation of ferritin to modulate MRI relaxivity. Biophys J 2008; 95: 342–351.
- 18 Matsumoto Y, Jasanoff A. T2 relaxation induced by clusters of superparamagnetic nanoparticles: Monte Carlo simulations. Magn Reson Imaging 2008; 26: 994–998.
- 19 Frank S, Lauterbur PC. Voltage-sensitive magnetic gels as magnetic resonance monitoring agents. Nature 1993; 363: 334–336.
- 20 Hirota M, Ohmuraya M, Baba H. The role of trypsin, trypsin inhibitor, and trypsin receptor in the onset and aggravation of pancreatitis. J Gastroenterol 2006; 41: 832–836.
- 21 Varon R, Havsteen BH, Vazquez A, Garcia M, Valero E, Garcia Canovas F. Kinetics of the trypsinogen activation by enterokinase and trypsin. J Theor Biol 1990; 145: 123–131.
- 22 Garcia-Moreno M, Havsteen BH, Varon R, Rix-Matzen H. Evaluation of the kinetic parameters of the activation of trypsinogen by trypsin. Biochim Biophys Acta 1991; 1080: 143–147.
- 23 Danon D, Goldstein L, Marikovsky Y, Skutelsky E. Use of cationized ferritin as a label of negative charges on cell surfaces. J Ultrastruct Res 1972; 38: 500–510.
- 24 Lee YM, Jeong Y, Kang HJ, Chung SJ, Chung BH. Cascade enzyme-linked immunosorbent assay (CELISA). Biosens Bioelectron 2009; 25: 251–255.
- 25 Levy M, Ellington AD. Exponential growth by cross-catalytic cleavage of deoxyribozymogens. Proc Natl Acad Sci USA 2003; 100: 6416–6421.
- 26 Huber R, Bode W. The structural basis of the activtion and action of trypsin. Am Chem Soc 1977; 11: 114–122.
- 27 Mikhailova AG, Likhareva VV, Teich N, Rumsh LD. The ways of realization of high specificity and efficiency of enteropeptidase. Protein Pept Lett 2007; 14: 227–232.
- 28 Guhaniyogi J, Sohar I, Das K, Stock AM, Lobel P. Crystal structure and autoactivation pathway of the precursor form of human tripeptidyl-peptidase 1, the enzyme deficient in late infantile ceroid lipofuscinosis. J Biol Chem 2009; 284: 3985–3997.
- 29 Stack CM, Donnelly S, Lowther J, Xu W, Collins PR, Brinen LS, Dalton JP. The major secreted cathepsin L1 protease of the liver fluke, Fasciola hepatica: a Leu-12 to Pro-12 replacement in the nonconserved C-terminal region of the prosegment prevents complete enzyme autoactivation and allows definition of the molecular events in prosegment removal. J Biol Chem 2007; 282: 16532–16543.
