Revealing the Distribution of Aggregation-Induced Emission Nanoparticles via Dual-Modality Imaging with Fluorescence and Mass Spectrometry

Aggregation-induced emission nanoparticles (AIE NPs) are widely used in the biomedical field. However, understanding the biological process of AIE NPs via fluorescence imaging is challenging because of the strong background and poor penetration depth. Herein, we present a novel dual-modality imaging strategy that combines fluorescence imaging and label-free laser desorption/ionization mass spectrometry imaging (LDI MSI) to map and quantify the biodistribution of AIE NPs (TPAFN-F127 NPs) by monitoring the intrinsic photoluminescence and mass spectrometry signal of the AIE molecule. We discovered that TPAFN-F127 NPs were predominantly distributed in the liver and spleen, and most gradually excreted from the body after 5 days. The accumulation and retention of TPAFN-F127 NPs in tumor sites were also confirmed in a tumor-bearing mouse model. As a proof of concept, the suborgan distribution of TPAFN-F127 NPs in the spleen was visualized by LDI MSI, and the results revealed that TPAFN-F127 NPs were mainly distributed in the red pulp of the spleen with extremely high concentrations within the marginal zone. The in vivo toxicity test demonstrated that TPAFN-F127 NPs are nontoxic for a long-term exposure. This dual-modality imaging strategy provides some insights into the fine distribution of AIE NPs and might also be extended to other polymeric NPs to evaluate their distribution and drug release behaviors in vivo.