Targeted, stimuli-responsive nanogels for atherosclerosis imaging and therapy Yu Qin, James D. E. T. Wilton-Ely Imperial College London, UK Atherosclerosis is a complex, continuously evolving, and long-lasting disease that severely threatens human health. The current understanding of the progression of atherosclerotic disease remains limited due to the lack of an efficient way to non-invasively monitor the progression of the disease over time. Poor diagnostic tools lead to an unmet need for guiding the management of atherosclerosis. Therefore, probes that can combine high sensitivity and selectivity with promising therapeutic action are of great significance for the early diagnosis and treatment of atherosclerosis. 1 Magnetic resonance imaging (MRI) is a leading non-invasive and ionizing radiation-free imaging modality. A range of MRI contrast agents has been developed, which can enhance the contrast between tissues. Contrast agents based on trivalent gadolinium (Gd 3+ ) are commonly used to diagnose and monitor diseases in the clinic. 2 Our research has developed two new gadolinium units, which deliver superior relaxivity performance compared to clinically-approved Dotarem TM . Dramatic enhancement of relaxivity is observed on attaching these contrast agents to gold nanoparticles using a dithiocarbamate (R 2 NCS 2 −) tether. 3,4 These encouraging results suggest that tethering such robust contrast agents, along with targeted units, to a nanoplatform offers great potential for early detection of high-risk atherosclerotic plaques. Nanogels are nanomaterials composed of a flexible polymeric network that can retain high volumes of water or biological fluids, and hence maintain their structure. This unique property is highly advantageous in the context of a nanoplatform for the delivery of drugs (as cargo within the nanogel) and gadolinium-based contrast agents, both of which benefit from an aqueous environment. This contribution describes the coupling of a novel gadolinium- based contrast agent to the surface of a crosslinked nanogel framework, allowing the delivery of the nanogel to the plaque to be visualized by MRI. It is proposed that surface functionalisation of the nanogel with a peptide that binds to tropoelastin, a marker for atherosclerosis, will deliver atherosclerosis targeting ability. This nanoplatform represents the first design that combines targeting, MRI imaging, and site-specific delivery of atherosclerosis therapy, and provides a promising strategy for the diagnosis and treatment of atherosclerosis. References 1. L. P. Dawson, M. Lum, N. Nerleker, S. J. Nicholls and J. Layland, J. Am. Coll. Cardiol., 2022, 79, 66-82. 2. D. Thi Kim Dung, S. Fukushima, T. Furukawa, H. Niioka, T. Sannomiya, K. Kobayashi, H. Yukawa, Y. Baba, M. Hashimoto and J. Miyake, Nanomaterials, 2016, 6, 163. 3. N. G. Chabloz, H. L. Perry, I. C. Yoon, A. J. Coulson, A. J. P. White, G. J. Stasiuk, R. M. Botnar and J. D. E. T. Wilton-Ely, Chem. - Eur. J., 2020, 26, 4552-4566. 4. N. G. Chabloz, M. N. Wenzel, H. L. Perry, I. C. Yoon, S. Molisso, G. J. Stasiuk, D. S. Elson, A. E. G. Cass and J. D. E. T. Wilton-Ely, Chem. - Eur. J., 2019, 25, 10895-10906.
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