Researchers at the Suzhou Institute of Biomedical Engineering and Technology (SIBET) of the Chinese Academy of Sciences have designed a novel type of red-emissive silicon nanodots (R-SiNDs) for mitochondrial dynamic tracking and blood-brain barrier penetration imaging. 

As the main site of aerobic respiration in eukaryotic cells, mitochondria not only provide energy for cells, but also are closely related to some cellular activities. The lack of mitochondrial function can also lead to diabetes, cardiac arrhythmia, Alzheimer's disease and many other diseases.

Fluorescent probes are considered the material of choice for mitochondrial imaging due to their good targeting and the advantage of real-time feedback. However, organic dyes usually have weak resistance to photobleaching, and less favorable ability to penetrate the blood-brain barrier (BBB).

In this study, the researchers led by DONG Wenfei adopted silicon nanodots (SiNDs), an emerging nanomaterial with low/non-toxicity and environmentally friendly properties, to exploit new fluorescent probes with both BBB penetration ability and excellent optical properties for long-term imaging.

"Fluorescent materials with red emissions possess special advantages for imaging, such as lower phototoxicity, high tissue permeability, and lower interference of autofluorescence from organisms," said DONG. "Small particle-size SiNDs with positive surface charge and amphiphilic properties meet the basic requirements for BBB penetration."

Their study showed that the R-SiNDs have excellent targeting and imaging ability towards living cell mitochondria. In addition, R-SiNDs can be used as monitors to achieve real-time visualization of mitochondrial dynamics due to their wonderful optical properties.

Using the robust tools of R-SiNDs, the researchers also observed the fusion and division processes of mitochondria. The results showed that the lipid droplets (LDs) were free from above the mitochondria to below and then wrapped by the mitochondria with the change of mitochondria shape. The changes in the position of the LDs and the morphology of the mitochondria resulted in a larger contact area between the two organelles, which was more favorable for the process of material exchange.

More interestingly, R-SiNDs, without any other modification, exhibited excellent BBB penetration ability and were accumulated in the central canal of the zebrafish spinal cord. "It is speculated that the small particle size, positive charge and amphiphilic properties together contribute to the BBB penetration of R-SiNDs, which also lays the foundation for the diagnosis of R-SiNDs in brain-related diseases," said LIU Yulu, first author of the study.

The R-SiNDs can not only be used to study mitochondrial dynamics, but also provide a reliable basis for the diagnosis of mitochondria-related brain diseases, which is of great value in biomedical applications, according to the researchers.

The study entitled "Red-emissive silicon nanodots with highly biocompatible for mitochondrial dynamic tracking and blood-brain barrier penetration imaging" was published in Sensors and Actuators B: Chemical.

This work was supported by the National Key R&D Program of China, and the National Natural Science Foundation of China, etc.

Fig. 1. Schematic illustration for the synthesis of the R-SiNDs, and the application for long-time mitochondrial dynamics imaging and zebrafish neurological imaging. (Image by SIBET) 

Fig. 2. (a) Confocal microscopy images of mitochondria after staining PANC-1 cells with R-SiNDs. (b) The fusion process of mitochondria labeled with R-SiNDs. (c) The fission process of mitochondria labeled with R-SiNDs. (d) Schematic illustration of mitochondrial fusion and fission. (e) Dual-color confocal microscopy images of PANC-1 cells after co-staining with R-SiNDs and BODIPY. (f) Schematic illustration of the mitochondria parcels LDs. Scale bar: 10 μm. (Image by SIBET)