CNBP researchers have published a new science paper reporting on a new zinc responsive delivery system with real-time intracellular sensing capabilities. Lead author of the publication is Dr Sabrina Heng (pictured).
Authors: Sabrina Heng, Xiaozhou Zhang, Jinxin Pei, Alaknanda Adwal, Philipp Reineck, Brant Gibson, Mark Hutchinson, Andrew Abell.
Abstract: A new spiropyran‐based stimuli‐responsive delivery system is presented that encapsulates and then releases an extraneous compound in response to elevated levels of Zn2+, a critical factor in cell apoptosis. A C12‐alkyl substituent on the spiropyran promotes self‐assembly into a micelle‐like nanocarrier in aqueous media, with nanoprecipitation and encapsulation of added payload. Zn2+ binding occurs to an appended bis(2‐pyridylmethyl)amine group at biologically relevant micromolar concentration. This leads to switching of the spiropyran (SP) isomer to the strongly fluorescent ring opened merocyanine‐Zn2+ (MC‐Zn2+) complex, with associated expansion of the nanocarriers to release the encapsulated payload. Payload release is demonstrated in solution and in HEK293 cells by encapsulation of a blue fluorophore, 7‐hydroxycoumarin, and monitoring its release using fluorescence spectroscopy and microscopy. Furthermore, we demonstrate the use of the nanocarriers to deliver a caspase inhibitor, Azure B, into apoptotic cells in response to an elevated Zn2+ concentration. This then inhibits intracellular caspase activity, as evidenced by confocal microscopy and in real‐time by time‐lapsed microscopy. Finally, the nanocarriers are shown to release an encapsulated proteasome inhibitor (5) in Zn2+‐treated breast carcinoma cell line models. This then inhibits intracellular proteasome and induces cytotoxicity to the carcinoma cells.