卟啉硫脲光氧化自脱硫合成的纤维化靶向T1 MRI造影剂。

IF 9.1 1区 化学 Q1 CHEMISTRY, ANALYTICAL
Kyle D W Vollett,Anlan Hong,Wanda W Janaeska,Daryn R Browne,Hai-Ling Margaret Cheng
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引用次数: 0

摘要

纤维化是一种无声的疾病,在晚期变得无法治疗和无法治愈,最终导致器官衰竭。早期干预可以减缓甚至逆转进展,但目前的非侵入性工具,如磁共振成像(MRI)和超声波,是非特异性的,只能检测晚期疤痕组织。我们提出了一种针对纤维化的非钆MRI造影剂,用于敏感和特异性的纤维化体内成像。与通过硬度或空死组织空间推断疤痕含量的传统方法不同,我们的试剂直接结合疤痕组织中多余的胶原基质。为了合成该试剂,我们通过首次证明卟啉光氧化自脱硫芳基硫脲键到稳定的尿素或胍键,将具有“MRI活性”的锰卟啉偶联到靶向纤维化的游离基卟啉上。该化合物对新瘢痕中酸溶性胶原具有高亲和力,可显著减少胶原凝胶的T1松弛时间。在小鼠弥漫性心肌纤维化模型中,纤维化靶向剂突出了常规晚期钆MRI未检测到的疤痕组织。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
A Fibrosis-Targeting T1 MRI Contrast Agent Synthesized via Photooxidative Self-Desulfurization of Porphyrin Thiourea.
Fibrosis is a silent disease that becomes untreatable and incurable in late stages, ultimately leading to organ failure. Early intervention can slow or even reverse progression, but current noninvasive tools like magnetic resonance imaging (MRI) and ultrasound are nonspecific and detect only advanced scar tissue. We present a fibrosis-targeting, nongadolinium MRI contrast agent for sensitive and specific in vivo imaging of fibrosis. Unlike conventional methods that infer scar content via stiffness or empty dead tissue space, our agent directly binds the excess collagen substrate of the scar tissue. To synthesize the agent, we conjugated an "MRI active" manganese porphyrin to a fibrosis-targeting free-base porphyrin via the first demonstration of porphyrin photooxidative self-desulfurization of aryl thiourea linkages to stable urea or guanidine linkages. The compound exhibited high affinity for acid-soluble collagen in a new scar and significantly reduced T1 relaxation time in collagen gels. In a mouse model of diffuse myocardial fibrosis, the fibrosis-targeting agent highlighted scar tissue that was undetected by conventional late-gadolinium MRI.
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来源期刊
ACS Sensors
ACS Sensors Chemical Engineering-Bioengineering
CiteScore
14.50
自引率
3.40%
发文量
372
期刊介绍: ACS Sensors is a peer-reviewed research journal that focuses on the dissemination of new and original knowledge in the field of sensor science, particularly those that selectively sense chemical or biological species or processes. The journal covers a broad range of topics, including but not limited to biosensors, chemical sensors, gas sensors, intracellular sensors, single molecule sensors, cell chips, and microfluidic devices. It aims to publish articles that address conceptual advances in sensing technology applicable to various types of analytes or application papers that report on the use of existing sensing concepts in new ways or for new analytes.
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