Redox-responsive Fluorescent Nanoparticles Based on Diselenide-containing AIEgens for Cell Imaging and Selective...

A fluorescent, diselenide-containing 9,10-distyrylanthracene (DSA) derivative (SeDSA) with aggregation-induced emission (AIE) characteristic was successfully synthesized and SeDSA nanoparticles (NPs) were prepared through a nanoprecipitation method. SeDSA could coassemble with an antitumor prodrug, diselenide-containing paclitaxel (SePTX), which could be obtained by precipitation, to form SeDSA-SePTX Co-NPs (Co-NPs). Molecular dynamics (MD) simulations reveal that the driving forces for the self-assembly behaviors of SeDSA NPs and SePTX NPs are π-π interactions and hydrophobic interactions, respectively, while the driving forces for Co-NPs include hydrophobic interactions between SeDSA and SePTX, π-π interactions between SeDSA molecules and hydrophobic interactions between SePTX molecules. Meanwhile, Se-Se bonds play a crucial role in balancing the intramolecular forces. These diselenide-containing nanoparticles (SeDSA NPs, SePTX NPs and Co-NPs) exhibit a high stability under physiological conditions and excellent reduction-sensitivity in the presence of the redox agent glutathione (GSH) because of the selenium-sulfur exchange reaction between diselenide and GSH. Both SeDSA NPs and Co-NPs show strong orange fluorescence emissions on the account of the AIE feature of SeDSA and they were easily internalized by HeLa and HepG2 cells. Distinctively, the Co-NPs combine the advantage of SeDSA and SePTX for cell imaging and antineoplastic activity, and exhibit selectivity of cytotoxicities between neoplasia cells and normal cells. This study highlights the development of diselenide-containing AIEgens as a unique approach to prepare uniform and stable fluorescent nanoparticles for the application in cell imaging and tumor treatment.