A tumor microenvironment dual responsive contrast agent for contrary contrast-magnetic resonance imaging and specific chemotherapy of tumors

作者：Lu, Yudie; Feng, Jie; Liang, Zhiyu; Lu, Xuanyi; Guo, Shuai; Huang, Lin; Xiong, Wei; Chen, Sijin; Zhou, Huimin; Ma, Xuehua; Xu, Yikai; Qiu, Xiaozhong; Wu, Aiguo; Chen, Xiaoyuan; Shen, Zheyu^*

来源：Nanoscale Horizons, 2022, 7(4): 403-413.

DOI：10.1039/d1nh00632k

• NEPHROGENIC SYSTEMIC FIBROSIS
• IRON-OXIDE NANOPARTICLES
• INORGANIC NANOPARTICLES
• GADOLINIUM
• RATS
• SIZE
• T-1

Development of magnetic resonance imaging (MRI) contrast agents (CAs) is still one of the research hotspots due to the inherent limitations of T-1- or T-2-weighted CAs and T-1/T-2 dual-mode CAs. To dramatically enhance the MRI contrast between tumors and normal tissues, we propose a new concept of contrary contrast-MRI (CC-MRI), whose specific definition is that CC-MRI CAs present a positive or negative signal at normal tissues, but show contrary signals at diseased tissues. To realize CC-MRI of tumors, we designed and developed a tumor microenvironment (TME) dual responsive CA (i.e., SA-FeGdNP-DOX@mPEG), which is almost not responsive under normal physiological conditions, but highly responsive to the acidic and reductive TME. Our SA-FeGdNP-DOX@mPEG shows a negative MRI signal under normal physiological conditions due to the high r(2) value (336.9 mM(-1) s(-1)) and high r(2)/r(1) ratio (18.4), but switches to a positive MRI signal in the TME because of the high r(1) value (20.32 mM(-1) s(-1)) and low r(2)/r(1) ratio (7.2). Our TME dual responsive SA-FeGdNP-DOX@mPEG significantly enhanced the contrast of MR images between tumors and livers, and the Delta SNR difference reached 501%. In addition, our SA-FeGdNP-DOX2@mPEG2 with tumor targetability and controlled DOX release responding to the TME was also used for tumor-specific chemotherapy with reduced side effects.

• 单位
  中国科学院; 南方医科大学; 中国科学院宁波材料技术与工程研究所