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|Title:||Spiropyran-based nanocarrier: a new Zn²⁺-responsive delivery system with real-time intracellular sensing capabilities|
|Other Titles:||Spiropyran-based nanocarrier: a new Zn2+ -responsive delivery system with real-time intracellular sensing capabilities|
|Citation:||Chemistry: A European Journal, 2019; 25(3):854-862|
|Sabrina Heng, Xiaozhou Zhang, Jinxin Pei, Alaknanda Adwal, Philipp Reineck, Brant C. Gibson, Mark R. Hutchinson and Andrew D. Abell|
|Abstract:||A 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.|
|Keywords:||Apoptosis; fluorescence; metal ions; payload delivery; spiropyran-based nanocarrier|
|Rights:||© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim|
|Appears in Collections:||Aurora harvest 8|
Chemistry and Physics publications
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