[nano] microfluidic synthesis of aggregation induced luminescence quantum dots less than 10 nm enhances tumor targeting and reduces liver interception

2020-09-14

After the discovery of aggregation induced luminescence (AIE) of conjugated molecules, researchers at home and abroad have developed a large number of AIE organic fluorescent probes for various fields. Among these AIE organic fluorescent probes, AIE luminescent group and phospholipid hybrid nanoprobes are representative, which are called AIE points. However, the size of AIE prepared by traditional method is larger than 25 nm.

Microfluidic nano biomedical laboratory of Biomedical Engineering Department of South University of science and technology and Li Kai team of Department of biomedical engineering of South University of science and technology of South China University of science and technology, through microfluidic technology, the size of AIE point was adjusted to below 10 nm for the first time. These AIE dots below 10 nm are called AIE quantum dots, which are different from the traditional AIE dots with larger particle size (> 25 nm). Compared with AIE dots > 25 nm, the quantum effects involved in these AIE QDs below 10 nm are not significant changes in physical properties, but are extended to significant changes in biological properties. For example, compared with AIE dots > 25 nm, AIE QDs can accelerate cell uptake by about 10 times in 6 h; AIE QDs can enhance tumor targeting by about 85%, reduce liver interception by about 35% and spleen interception by about 55%. This biological quantum effect indicates that AIE QDs may be more suitable for cell labeling and cancer diagnosis and treatment than traditional AIE dots > 25 nm.

How to prepare AIE quantum dots below 10 nm? A microfluidic chip with a double helix mixed pipe (300 μ m wide and 60 μ m high) was developed in the early work. After improving the preparation process, they increased the flow rate in the pipeline from 20 ml / h to 240 ml / h. It has been proved by PLGA and phospholipid materials that the mixing time can be shortened by the bending pipe (double helix), and the mixing time can be shortened by increasing the flow rate. These two factors can significantly reduce the particle size of PLGA phospholipid hybrid nanoparticles. When PLGA macromolecules were replaced by AIE conjugated small molecules, the particle size of the products decreased to less than 10 nm. Four AIE conjugated materials with different molecular structures can reproduce AIE quantum dots below 10 nm. The fluorescence range of these four AIE conjugated materials covers the green to near-infrared region. It is suggested that this microfluidic method for preparing AIE with particle size less than 10 nm may be generally applicable to various AIE conjugated materials with different functions.

 

图1. 微流控合成小于10 nm的AIE量子点。图片来源:Angew. Chem. Int. Ed.

 

图2. AIE量子点(QDs)和AIE点(Dots)的细胞摄取效率比较。图片来源:Angew. Chem. Int. Ed.

 

图3. AIE量子点和AIE点对小鼠肿瘤的二区荧光成像。图片来源:Angew. Chem. Int. Ed.

 

This achievement was recently published in angelwandte Chemistry International Edition. The first authors of the paper are Li Xuanyu, a doctoral candidate from the National Center for nanoscience, and cha Menglei, a master's student from South University of science and technology.