Heng, S.Zhang, X.Pei, J.Adwal, A.Reineck, P.Gibson, B.C.Hutchinson, M.R.Abell, A.D.2019-02-202019-02-202019Chemistry - A European Journal, 2019; 25(3):854-8620947-65391521-3765http://hdl.handle.net/2440/117844A new spiropyran-based stimuli-responsive delivery system is fabricated. It 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, the use of the nanocarriers to deliver a caspase inhibitor, Azure B, into apoptotic cells in response to an elevated Zn²⁺ concentration is demonstrated. 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.en© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, WeinheimApoptosis; fluorescence; metal ions; payload delivery; spiropyran-based nanocarrierJournal article003010287010.1002/chem.2018048160004562808000252-s2.0-85058453966448401Pei, J. [0000-0003-2453-929X]Adwal, A. [0000-0001-9441-5407]Hutchinson, M.R. [0000-0003-2154-5950]Abell, A.D. [0000-0002-0604-2629]