"Light-On" Fluorescent Nanoprobes for Monitoring Dynamic Distribution of Cellular Nucleolin During Pyroptosis

Nucleolin (NCL) is a multifunctional nuclear protein that plays significant roles in regulating physiological activities of the cells. However, it remains a challenge to monitor the dynamic distribution and expression of nucleolin within living cells during cell stress processes directly. Here, we designed "turn-on" fluorescent nanoprobes composed of specific AS1411 aptamer and nucleus-targeting peptide on gold nanoparticles (AuNPs) to effectively capture and track the NCL distribution and expression during pyroptosis triggered by electrical stimulation (ES). The distribution of nucleolin in the cell membrane and nucleus can be easily observed by simply changing the particle size of the nanoprobes. The present strategy exhibits obvious advantages such as simple operation, low cost, time saving, and suitability for living cell imaging. The ES can induce cancer cell pyroptosis controllably and selectively, with less harm to the viability of normal cells. The palpable cell nuclear stress responses of cancerous cells, including nucleus wrinkling and nucleolus fusion after ES at 1.0 V were obviously observed. Compared with normal cells (MCF-10A), NCL is overexpressed within cancerous cells (MCF-7 cells) using the as-designed nanoprobes, and the ES can effectively inhibit NCL expression within cancerous cells. The developed NCL sensing platform and ES-based methods hold great potential for cellular studies of cancer-related diseases.