Xilan Li, Yun Liu*, Xiaowei Qi, Shilin Xiao, Zhongsheng Xu, Zhixian Yuan, Qi Liu, Haisheng Li, Siyuan Ma, Tengfei Liu, Yong Huang, Xiaorong Zhang, Xiao Zhang, Zhengwei Mao*, Gaoxing Luo*, Jun Deng*

Abstract

Imaging-guided real-time monitoring of the treatment process of inflammatory diseases is important for the timely adjustment of treatment planning to lower unnecessary side effects and improve treatment outcomes. However, it is difficult to reflect the dynamic changes of inflammation in vivo with enough tissue penetration depth. Here a novel nanotheranostic agent (denominated TMSN@PM) with platelet membrane (PM)-coated, tempol-grafted, manganese-doped, mesoporous silica nanoparticles is developed. The PM endows the TMSN@PM with the ability to target inflammation sites, which are verified by fluorescence imaging with Cyanine5 carboxylic acid (Cy5)-labeled TMSN@PM. Under the inflammatory environment (mild acidity and excess reactive oxygen species (ROS)), TMSN@PM can scavenge the excess ROS, thereby alleviating inflammation, degrade, and release manganese ions for enhanced magnetic resonance imaging (MRI). The relaxation changes (ΔR1 ) are almost linearly correlated with the concentration of H2 O2 , which can reflect the degree of inflammation. This method offers a non-invasive imaging-based strategy for early prediction of the therapeutic outcomes in inflammatory therapy, which may contribute to precision medicine in terms of prognostic stratification and therapeutic planning in future.

Keywords: activatable nanoprobes; inflammation; magnetic resonance imaging; reactive oxygen species; theranostics.