A nitroxides-based macromolecular MRI contrast agent with an extraordinary longitudinal relaxivity for tumor imaging via clinical T1WI SE sequence

作者：Shiwei Guo, Xiaoming Wang, Zhiqian Li, Dayi Pan, Yan Dai, Yun Ye, Xiaohe Tian, Zhongwei Gu, Qiyong Gong, Hu Zhang, Kui Luo · 发表于：Journal of Nanobiotechnology · 年份：2021 · DOI：10.1186/s12951-021-00990-6 · 被引用次数：20 · 研究领域：Electron Spin Resonance Studies、Nanoparticle-Based Drug Delivery、Lanthanide and Transition Metal Complexes

Abstract Background Macromoleculization of nitroxides has been an effective strategy to improve low relaxivities and poor in vivo stability, however, nitroxides-based metal-free magnetic resonance imaging (MRI) macromolecular contrast agents (mCAs) are still under-performed. These mCAs do not possess a high nitroxides content sufficient for a cumulative effect. Amphiphilic nanostructures in these mCAs are not stable enough for highly efficient protection of nitroxides and do not have adequate molecular flexibility for full contact of the paramagnetic center with the peripheral water molecules. In addition, these mCAs still raise the concerns over biocompatibility and biodegradability due to the presence of macromolecules in these mCAs. Results Herein, a water-soluble biodegradable nitroxides-based mCA (Linear pDHPMA-mPEG-Ppa-PROXYL) was prepared via covalent conjugation of a nitroxides (2,2,5,5-tetramethyl-1-pyrrolidinyl- N -oxyl, PROXYL) onto an enzyme-sensitive linear di-block poly[ N -(1, 3-dihydroxypropyl) methacrylamide] (pDHPMA). A high content of PROXYL up to 0.111 mmol/g in Linear pDHPMA-mPEG-Ppa-PROXYL was achieved and a stable nano-sized self-assembled aggregate in an aqueous environment (ca. 23 nm) was formed. Its longitudinal relaxivity ( r 1 = 0.93 mM − 1 s − 1 ) was the highest compared to reported nitroxides-based mCAs. The blood retention time of PROXYL from the prepared mCA in vivo was up to ca. 8 h and great accumulation of the mCA was realized in the tumor ...