{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T06:19:45Z","timestamp":1791353985729,"version":"4.3.1"},"reference-count":54,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2015,10,6]],"date-time":"2015-10-06T00:00:00Z","timestamp":1444089600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2015,10,6]],"date-time":"2015-10-06T00:00:00Z","timestamp":1444089600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Personalized cancer medicine requires measurement of therapeutic efficacy as early as possible, which is optimally achieved by three-dimensional imaging given the heterogeneity of cancer. Magnetic resonance imaging (MRI) can obtain images of both anatomy and cellular responses, if acquired with a molecular imaging contrast agent. The poor sensitivity of MRI has limited the development of activatable molecular MR contrast agents. To overcome this limitation of molecular MRI, a novel implementation of our caspase-3-sensitive nanoaggregation MRI (C-SNAM) contrast agent is reported. C-SNAM is triggered to self-assemble into nanoparticles in apoptotic tumor cells and effectively amplifies molecular level changes through nanoaggregation, enhancing tissue retention and spin-lattice relaxivity. At one-tenth the current clinical dose of contrast agent and following a single imaging session, C-SNAM MRI accurately measured the response of tumors to either metronomic chemotherapy or radiation therapy, where the degree of signal enhancement is prognostic of long-term therapeutic efficacy. Importantly, C-SNAM is inert to immune activation, permitting radiation therapy monitoring.<\/jats:p>","DOI":"10.1038\/srep14759","type":"journal-article","created":{"date-parts":[[2015,10,6]],"date-time":"2015-10-06T09:25:51Z","timestamp":1444123551000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":44,"title":["Molecular Magnetic Resonance Imaging of Tumor Response to Therapy"],"prefix":"10.1038","volume":"5","author":[{"given":"Adam J.","family":"Shuhendler","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deju","family":"Ye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimberly D.","family":"Brewer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdalena","family":"Bazalova-Carter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyung-Hyun","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Kempen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.","family":"Dane Wittrup","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward E.","family":"Graves","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Rutt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianghong","family":"Rao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2015,10,6]]},"reference":[{"key":"BFsrep14759_CR1","doi-asserted-by":"publisher","first-page":"e8","DOI":"10.2349\/biij.2.2.e8","volume":"2","author":"A Hengerer","year":"2006","unstructured":"Hengerer, A. & Grimm, J. Molecular magnetic resonance imaging. Biomed Imaging Interv J 2, e8 (2006).","journal-title":"Biomed Imaging Interv J"},{"key":"BFsrep14759_CR2","first-page":"242","volume":"1766","author":"AA Neves","year":"2006","unstructured":"Neves, A. A. & Brindle, K. M. Assessing responses to cancer therapy using molecular imaging. Biochim Biophys Acta 1766, 242\u2013261 (2006).","journal-title":"Biochim Biophys Acta"},{"key":"BFsrep14759_CR3","doi-asserted-by":"publisher","first-page":"1","DOI":"10.2967\/jnumed.112.114264","volume":"55","author":"AA Neves","year":"2014","unstructured":"Neves, A. A. & Brindle, K. M. Imaging cell death. J Nucl Med 55, 1\u20134 (2014).","journal-title":"J Nucl Med"},{"key":"BFsrep14759_CR4","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1016\/j.critrevonc.2008.07.012","volume":"72","author":"CD Marcus","year":"2009","unstructured":"Marcus, C. D. et al. Imaging techniques to evaluate the response to treatment in oncology: current standards and perspectives. Crit Rev Oncol Hematol 72, 217\u2013238 (2009).","journal-title":"Crit Rev Oncol Hematol"},{"key":"BFsrep14759_CR5","doi-asserted-by":"publisher","first-page":"533","DOI":"10.1093\/jjco\/hyg093","volume":"33","author":"JO Park","year":"2003","unstructured":"Park, J. O. et al. Measuring response in solid tumors: comparison of RECIST and WHO response criteria. Jpn J Clin Oncol 33, 533\u2013537 (2003).","journal-title":"Jpn J Clin Oncol"},{"key":"BFsrep14759_CR6","doi-asserted-by":"publisher","first-page":"228","DOI":"10.1016\/j.ejca.2008.10.026","volume":"45","author":"EA Eisenhauer","year":"2009","unstructured":"Eisenhauer, E. A. et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 45, 228\u2013247 (2009).","journal-title":"Eur J Cancer"},{"key":"BFsrep14759_CR7","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1093\/jnci\/92.3.205","volume":"92","author":"P Therasse","year":"2000","unstructured":"Therasse, P. et al. New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst 92, 205\u2013216 (2000).","journal-title":"J Natl Cancer Inst"},{"key":"BFsrep14759_CR8","doi-asserted-by":"publisher","first-page":"1301","DOI":"10.1016\/j.mri.2012.06.009","volume":"30","author":"BF Kurland","year":"2012","unstructured":"Kurland, B. F. et al. Promise and pitfalls of quantitative imaging in oncology clinical trials. Magn Reson Imaging 30, 1301\u20131312 (2012).","journal-title":"Magn Reson Imaging"},{"key":"BFsrep14759_CR9","doi-asserted-by":"publisher","first-page":"S111","DOI":"10.1259\/bjr\/50577981","volume":"76","author":"KM Brindle","year":"2003","unstructured":"Brindle, K. M. Molecular imaging using magnetic resonance: new tools for the development of tumour therapy. Br J Radiol 76 Spec No 2, S111\u20137 (2003).","journal-title":"Br J Radiol"},{"key":"BFsrep14759_CR10","doi-asserted-by":"publisher","first-page":"496","DOI":"10.1056\/NEJMra050276","volume":"354","author":"ME Juweid","year":"2006","unstructured":"Juweid, M. E. & Cheson, B. D. Positron-emission tomography and assessment of cancer therapy. N Engl J Med 354, 496\u2013507 (2006).","journal-title":"N Engl J Med"},{"key":"BFsrep14759_CR11","doi-asserted-by":"publisher","first-page":"887","DOI":"10.1055\/s-2003-43482","volume":"35","author":"L Aabakken","year":"2003","unstructured":"Aabakken, L. Endoscopic tumor diagnosis and treatment. Endoscopy 35, 887\u2013890 (2003).","journal-title":"Endoscopy"},{"key":"BFsrep14759_CR12","doi-asserted-by":"publisher","first-page":"88","DOI":"10.2967\/jnumed.108.054205","volume":"50","author":"S Ben-Haim","year":"2009","unstructured":"Ben-Haim, S. & Ell, P. 18F-FDG PET and PET\/CT in the evaluation of cancer treatment response. J Nucl Med 50, 88\u201399 (2009).","journal-title":"J Nucl Med"},{"key":"BFsrep14759_CR13","doi-asserted-by":"publisher","first-page":"10511","DOI":"10.1002\/anie.201303422","volume":"52","author":"B Shen","year":"2013","unstructured":"Shen, B. et al. Positron emission tomography imaging of drug-induced tumor apoptosis with a caspase-triggered nanoaggregation probe. Angew Chem Int Ed Engl 52, 10511\u201310514 (2013).","journal-title":"Angew Chem Int Ed Engl"},{"key":"BFsrep14759_CR14","doi-asserted-by":"publisher","first-page":"3845","DOI":"10.1039\/C4SC01392A","volume":"5","author":"D Ye","year":"2014","unstructured":"Ye, D. et al. Caspase-responsive smart gadolinium-based contrast agent for magnetic resonance imaging of drug-induced apoptosis. Chem. Sci . 5, 3845\u20133852 (2014).","journal-title":"Chem. Sci"},{"key":"BFsrep14759_CR15","doi-asserted-by":"publisher","first-page":"519","DOI":"10.1038\/nchem.1920","volume":"6","author":"D Ye","year":"2014","unstructured":"Ye, D. et al. Bioorthogonal cyclization-mediated in situ self-assembly of small-molecule probes for imaging caspase activity in vivo. Nat Chem 6, 519\u2013526 (2014).","journal-title":"Nat Chem"},{"key":"BFsrep14759_CR16","doi-asserted-by":"publisher","first-page":"779","DOI":"10.1097\/00004424-199811000-00002","volume":"33","author":"RS Ranganathan","year":"1998","unstructured":"Ranganathan, R. S. et al. New multimeric magnetic resonance imaging agents. Invest Radiol 33, 779\u2013797 (1998).","journal-title":"Invest Radiol"},{"key":"BFsrep14759_CR17","doi-asserted-by":"publisher","first-page":"1551","DOI":"10.1101\/gad.12.11.1551","volume":"12","author":"V Cryns","year":"1998","unstructured":"Cryns, V. & Yuan, J. Proteases to die for. Genes Dev 12, 1551\u20131570 (1998).","journal-title":"Genes Dev"},{"key":"BFsrep14759_CR18","doi-asserted-by":"publisher","first-page":"467","DOI":"10.1667\/RR2576.1","volume":"177","author":"A Haimovitz-Friedman","year":"2012","unstructured":"Haimovitz-Friedman, A., Yang, T. J., Thin, T. H. & Verheij, M. Imaging radiotherapy-induced apoptosis. Radiat Res 177, 467\u2013482 (2012).","journal-title":"Radiat Res"},{"key":"BFsrep14759_CR19","doi-asserted-by":"publisher","first-page":"2275","DOI":"10.1002\/anie.201006140","volume":"50","author":"D Ye","year":"2011","unstructured":"Ye, D., Liang, G., Ma, M. L. & Rao, J. Controlling intracellular macrocyclization for the imaging of protease activity. Angew Chem Int Ed Engl 50, 2275\u20132279 (2011).","journal-title":"Angew Chem Int Ed Engl"},{"key":"BFsrep14759_CR20","doi-asserted-by":"crossref","first-page":"e12027","DOI":"10.1200\/jco.2013.31.15_suppl.e12027","volume":"31","author":"M Frolova","year":"2013","unstructured":"Frolova, M. et al. Neoadjuvant chemotherapy with metronomic doxorubicin, cyclophosphamide and capecitabine in patients with locally advanced (LA) triple-negative breast cancer (TNBC). J Clin Oncol 31, e12027 (2013).","journal-title":"J Clin Oncol"},{"key":"BFsrep14759_CR21","first-page":"150","volume":"3","author":"BWJ Loo","year":"2011","unstructured":"Loo, B. W. J. Stereotactic ablative radiotherapy (SABR) for lung cancer: What does the future hold? J Thorac Dis 3, 150\u2013152 (2011).","journal-title":"J Thorac Dis"},{"key":"BFsrep14759_CR22","doi-asserted-by":"publisher","first-page":"854","DOI":"10.1148\/radiol.2463070471","volume":"246","author":"AS Krishnan","year":"2008","unstructured":"Krishnan, A. S. et al. Detection of cell death in tumors by using MR imaging and a gadolinium-based targeted contrast agent. Radiology 246, 854\u2013862 (2008).","journal-title":"Radiology"},{"key":"BFsrep14759_CR23","doi-asserted-by":"publisher","first-page":"1419","DOI":"10.1021\/nl070126v","volume":"7","author":"AA Neves","year":"2007","unstructured":"Neves, A. A. et al. A paramagnetic nanoprobe to detect tumor cell death using magnetic resonance imaging. Nano Lett 7, 1419\u20131423 (2007).","journal-title":"Nano Lett"},{"key":"BFsrep14759_CR24","doi-asserted-by":"publisher","first-page":"3914","DOI":"10.1158\/1078-0432.CCR-12-3814","volume":"19","author":"QD Nguyen","year":"2013","unstructured":"Nguyen, Q. D. et al. Temporal and spatial evolution of therapy-induced tumor apoptosis detected by caspase-3-selective molecular imaging. Clin Cancer Res 19, 3914\u20133924 (2013).","journal-title":"Clin Cancer Res"},{"key":"BFsrep14759_CR25","doi-asserted-by":"publisher","first-page":"e91694","DOI":"10.1371\/journal.pone.0091694","volume":"9","author":"TH Witney","year":"2014","unstructured":"Witney, T. H., Fortt, R. R. & Aboagye, E. O. Preclinical assessment of carboplatin treatment efficacy in lung cancer by 18F-ICMT-11-positron emission tomography. PLoS One 9, e91694 (2014).","journal-title":"PLoS One"},{"key":"BFsrep14759_CR26","doi-asserted-by":"publisher","first-page":"1369","DOI":"10.1038\/nm1202-794","volume":"8","author":"AG Niethammer","year":"2002","unstructured":"Niethammer, A. G. et al. A DNA vaccine against VEGF receptor 2 prevents effective angiogenesis and inhibits tumor growth. Nat Med 8, 1369\u20131375 (2002).","journal-title":"Nat Med"},{"key":"BFsrep14759_CR27","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1016\/j.nucmedbio.2010.08.013","volume":"38","author":"KD Orcutt","year":"2011","unstructured":"Orcutt, K. D. et al. Engineering an antibody with picomolar affinity to DOTA chelates of multiple radionuclides for pretargeted radioimmunotherapy and imaging. Nucl Med Biol 38, 223\u2013233 (2011).","journal-title":"Nucl Med Biol"},{"key":"BFsrep14759_CR28","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1093\/protein\/gzs096","volume":"26","author":"PJ Yazaki","year":"2013","unstructured":"Yazaki, P. J. et al. A series of anti-CEA\/anti-DOTA bispecific antibody formats evaluated for pre-targeting: comparison of tumor uptake and blood clearance. Protein Eng Des Sel 26, 187\u2013193 (2013).","journal-title":"Protein Eng Des Sel"},{"key":"BFsrep14759_CR29","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1038\/nrc1560","volume":"5","author":"JM Brown","year":"2005","unstructured":"Brown, J. M. & Attardi, L. D. The role of apoptosis in cancer development and treatment response. Nat Rev Cancer 5, 231\u2013237 (2005).","journal-title":"Nat Rev Cancer"},{"key":"BFsrep14759_CR30","doi-asserted-by":"publisher","first-page":"631","DOI":"10.2174\/1566524033479483","volume":"3","author":"JL Townson","year":"2003","unstructured":"Townson, J. L., Naumov, G. N. & Chambers, A. F. The role of apoptosis in tumor progression and metastasis. Curr Mol Med 3, 631\u2013642 (2003).","journal-title":"Curr Mol Med"},{"key":"BFsrep14759_CR31","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1038\/73780","volume":"18","author":"AY Louie","year":"2000","unstructured":"Louie, A. Y. et al. In vivo visualization of gene expression using magnetic resonance imaging. Nat Biotechnol 18, 321\u2013325 (2000).","journal-title":"Nat Biotechnol"},{"key":"BFsrep14759_CR32","doi-asserted-by":"publisher","first-page":"781","DOI":"10.1002\/nbm.2870","volume":"26","author":"C Tu","year":"2013","unstructured":"Tu, C. & Louie, A. Y. Strategies for the development of gadolinium-based \u2018q\u2019-activatable MRI contrast agents. NMR Biomed 26, 781\u2013787 (2013).","journal-title":"NMR Biomed"},{"key":"BFsrep14759_CR33","doi-asserted-by":"publisher","first-page":"473","DOI":"10.1148\/radiol.2402050994","volume":"240","author":"JW Chen","year":"2006","unstructured":"Chen, J. W., Querol Sans, M., Bogdanov, A. J. & Weissleder, R. Imaging of myeloperoxidase in mice by using novel amplifiable paramagnetic substrates. Radiology 240, 473\u2013481 (2006).","journal-title":"Radiology"},{"key":"BFsrep14759_CR34","doi-asserted-by":"publisher","first-page":"4484","DOI":"10.1158\/1078-0432.CCR-11-0575","volume":"17","author":"A Kleijn","year":"2011","unstructured":"Kleijn, A. et al. Distinguishing inflammation from tumor and peritumoral edema by myeloperoxidase magnetic resonance imaging. Clin Cancer Res 17, 4484\u20134493 (2011).","journal-title":"Clin Cancer Res"},{"key":"BFsrep14759_CR35","doi-asserted-by":"publisher","first-page":"592","DOI":"10.1161\/CIRCULATIONAHA.108.813998","volume":"120","author":"JA Ronald","year":"2009","unstructured":"Ronald, J. A. et al. Enzyme-sensitive magnetic resonance imaging targeting myeloperoxidase identifies active inflammation in experimental rabbit atherosclerotic plaques. Circulation 120, 592\u2013599 (2009).","journal-title":"Circulation"},{"key":"BFsrep14759_CR36","doi-asserted-by":"publisher","first-page":"781","DOI":"10.1016\/0360-3016(95)00214-8","volume":"33","author":"WC Dewey","year":"1995","unstructured":"Dewey, W. C., Ling, C. C. & Meyn, R. E. Radiation-induced apoptosis: relevance to radiotherapy. Int J Radiat Oncol Biol Phys 33, 781\u2013796 (1995).","journal-title":"Int J Radiat Oncol Biol Phys"},{"key":"BFsrep14759_CR37","doi-asserted-by":"publisher","first-page":"75","DOI":"10.2307\/3578399","volume":"135","author":"LC Stephens","year":"1993","unstructured":"Stephens, L. C., Hunter, N. R., Ang, K. K., Milas, L. & Meyn, R. E. Development of apoptosis in irradiated murine tumors as a function of time and dose. Radiat Res 135, 75\u201380 (1993).","journal-title":"Radiat Res"},{"key":"BFsrep14759_CR38","doi-asserted-by":"publisher","first-page":"595","DOI":"10.1667\/RR1129.1","volume":"169","author":"ET Brown","year":"2008","unstructured":"Brown, E. T., Robinson-Benion, C. & Holt, J. T. Radiation enhances caspase 3 cleavage of Rad51 in BRCA2-defective cells. Radiat Res 169, 595\u2013601 (2008).","journal-title":"Radiat Res"},{"key":"BFsrep14759_CR39","doi-asserted-by":"publisher","first-page":"2986","DOI":"10.1128\/MCB.19.4.2986","volume":"19","author":"Y Huang","year":"1999","unstructured":"Huang, Y. et al. Role for caspase-mediated cleavage of Rad51 in induction of apoptosis by DNA damage. Mol Cell Biol 19, 2986\u20132997 (1999).","journal-title":"Mol Cell Biol"},{"key":"BFsrep14759_CR40","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1186\/1748-717X-5-85","volume":"5","author":"B Pinar","year":"2010","unstructured":"Pinar, B. et al. Radiation induced apoptosis and initial DNA damage are inversely related in locally advanced breast cancer patients. Radiat Oncol 5, 85 (2010).","journal-title":"Radiat Oncol"},{"key":"BFsrep14759_CR41","doi-asserted-by":"publisher","first-page":"81S","DOI":"10.2967\/jnumed.107.045898","volume":"49","author":"FG Blankenberg","year":"2008","unstructured":"Blankenberg, F. G. In vivo detection of apoptosis. J Nucl Med 49 Suppl 2, 81S\u201395S (2008).","journal-title":"J Nucl Med"},{"key":"BFsrep14759_CR42","doi-asserted-by":"publisher","first-page":"1241","DOI":"10.1038\/nm1101-1241","volume":"7","author":"M Zhao","year":"2001","unstructured":"Zhao, M., Beauregard, D. A., Loizou, L., Davletov, B. & Brindle, K. M. Non-invasive detection of apoptosis using magnetic resonance imaging and a targeted contrast agent. Nat Med 7, 1241\u20131244 (2001).","journal-title":"Nat Med"},{"key":"BFsrep14759_CR43","doi-asserted-by":"publisher","first-page":"774","DOI":"10.2967\/jnumed.108.061283","volume":"50","author":"I Madar","year":"2009","unstructured":"Madar, I. et al. Detection and quantification of the evolution dynamics of apoptosis using the PET voltage sensor 18F-fluorobenzyl triphenyl phosphonium. J Nucl Med 50, 774\u2013780 (2009).","journal-title":"J Nucl Med"},{"key":"BFsrep14759_CR44","doi-asserted-by":"publisher","first-page":"2089","DOI":"10.1007\/s10495-006-0282-7","volume":"11","author":"R Aloya","year":"2006","unstructured":"Aloya, R. et al. Molecular imaging of cell death in vivo by a novel small molecule probe. Apoptosis 11, 2089\u20132101 (2006).","journal-title":"Apoptosis"},{"key":"BFsrep14759_CR45","doi-asserted-by":"publisher","first-page":"729","DOI":"10.1161\/CIRCIMAGING.111.966374","volume":"4","author":"S Huang","year":"2011","unstructured":"Huang, S. et al. Molecular MRI of acute necrosis with a novel DNA-binding gadolinium chelate: kinetics of cell death and clearance in infarcted myocardium. Circ Cardiovasc Imaging 4, 729\u2013737 (2011).","journal-title":"Circ Cardiovasc Imaging"},{"key":"BFsrep14759_CR46","doi-asserted-by":"publisher","first-page":"4663","DOI":"10.1074\/jbc.M508342200","volume":"281","author":"VA Patel","year":"2006","unstructured":"Patel, V. A. et al. Apoptotic cells, at all stages of the death process, trigger characteristic signaling events that are divergent from and dominant over those triggered by necrotic cells: Implications for the delayed clearance model of autoimmunity. J Biol Chem 281, 4663\u20134670 (2006).","journal-title":"J Biol Chem"},{"key":"BFsrep14759_CR47","unstructured":"Administration, F. A. D. Guidance for industry: estimating the maximum safe starting dose in initial clinical trials for therapeutics in adult health vounteers. Center for Drug Evalualtion and Research, US Department of Health and Human Services: Washington, WA, USA (2005)."},{"key":"BFsrep14759_CR48","doi-asserted-by":"crossref","unstructured":"Maravilla, K. R. et al. Are There Differences between Macrocyclic Gadolinium Contrast Agents for Brain Tumor Imaging? Results of a Multicenter Intraindividual Crossover Comparison of Gadobutrol with Gadoteridol (the TRUTH Study). AJNR Am J Neuroradiol (2014).","DOI":"10.3174\/ajnr.A4154"},{"key":"BFsrep14759_CR49","doi-asserted-by":"publisher","first-page":"454","DOI":"10.1016\/j.nantod.2013.06.001","volume":"8","author":"S Chapman","year":"2013","unstructured":"Chapman, S. et al. Nanoparticles for cancer imaging: The good, the bad and the promise. Nano Today 8, 454\u2013460 (2013).","journal-title":"Nano Today"},{"key":"BFsrep14759_CR50","doi-asserted-by":"publisher","first-page":"5822","DOI":"10.1016\/j.biomaterials.2014.03.054","volume":"35","author":"E Jin","year":"2014","unstructured":"Jin, E. & Lu, Z. R. Biodegradable iodinated polydisulfides as contrast agents for CT angiography. Biomaterials 35, 5822\u20135829 (2014).","journal-title":"Biomaterials"},{"key":"BFsrep14759_CR51","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1021\/nn4054107","volume":"8","author":"X Wu","year":"2014","unstructured":"Wu, X. et al. Synthesis and evaluation of a nanoglobular dendrimer 5-aminosalicylic Acid conjugate with a hydrolyzable schiff base spacer for treating retinal degeneration. ACS Nano 8, 153\u2013161 (2014).","journal-title":"ACS Nano"},{"key":"BFsrep14759_CR52","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1093\/protein\/gzp077","volume":"23","author":"KD Orcutt","year":"2010","unstructured":"Orcutt, K. D. et al. A modular IgG-scFv bispecific antibody topology. Protein Eng Des Sel 23, 221\u2013228 (2010).","journal-title":"Protein Eng Des Sel"},{"key":"BFsrep14759_CR53","doi-asserted-by":"publisher","first-page":"6718","DOI":"10.1182\/blood-2011-08-375188","volume":"118","author":"KT Kang","year":"2011","unstructured":"Kang, K. T., Allen, P. & Bischoff, J. Bioengineered human vascular networks transplanted into secondary mice reconnect with the host vasculature and re-establish perfusion. Blood 118, 6718\u20136721 (2011).","journal-title":"Blood"},{"key":"BFsrep14759_CR54","doi-asserted-by":"publisher","first-page":"671","DOI":"10.1038\/nmeth.2089","volume":"9","author":"CA Schneider","year":"2012","unstructured":"Schneider, C. A., Rasband, W. S. & Eliceiri, K. W. NIH Image to ImageJ: 25 years of image analysis. Nat Methods 9, 671\u2013675 (2012).","journal-title":"Nat Methods"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/srep14759.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep14759","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep14759.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,5]],"date-time":"2023-01-05T16:09:12Z","timestamp":1672934952000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/srep14759"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,10,6]]},"references-count":54,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2015,12,7]]}},"alternative-id":["BFsrep14759"],"URL":"https:\/\/doi.org\/10.1038\/srep14759","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,10,6]]},"assertion":[{"value":"8 April 2015","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 September 2015","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 October 2015","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"14759"}}