Carbon nanodots as a red emissive fluorescent probe for the super-resolution microscopy of DNA dynamics during paclitaxel treatment

Abstract

Paclitaxel is a commonly used frontline chemotherapeutic drug for cancer treatment. It is known to be functional by arresting the microtubule disassembly during mitosis. Recently, a non-mitotic pathway has been evolving and thus contemplating the mitotic mechanism. Here, using super-resolution microscopy (SRM), we directly visualized the nuclear dynamics and unveiled the mechanism of paclitaxel treatment. A new class of non-toxic, biocompatible and highly fluorescent carbon nanodots (CNDs) were used as a fluorescent probe that were highly capable to directly stain the nuclear DNA, capture the SRM imaging of chromosome and the chromatin structures. Apart from SRM imaging of chromosomes during all stages of normal mitotic cell division, CNDs successfully visualized the formation of lagging, mis-segregated and bridging chromosomes which leads to the multi-micronucleus formation upon paclitaxel treatment. A detailed chromatin remodelling analysis suggested that heterochromatin played an important role in the formation of condensed multi-micronucleus, ultimately leading to cell death. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC="FIGDIR/small/620846v1_ufig1.gif" ALT="Figure 1"> View larger version (59K): org.highwire.dtl.DTLVardef@1d5bb12org.highwire.dtl.DTLVardef@ecd313org.highwire.dtl.DTLVardef@15bb3corg.highwire.dtl.DTLVardef@b79273_HPS_FORMAT_FIGEXP M_FIG C_FIG