Spiropyran-based nanocarrier: a new Zn²⁺-responsive delivery system with real-time intracellular sensing capabilities
Date
2019
Authors
Heng, S.
Zhang, X.
Pei, J.
Adwal, A.
Reineck, P.
Gibson, B.C.
Hutchinson, M.R.
Abell, A.D.
Editors
Advisors
Journal Title
Journal ISSN
Volume Title
Type:
Journal article
Citation
Chemistry - A European Journal, 2019; 25(3):854-862
Statement of Responsibility
Sabrina Heng, Xiaozhou Zhang, Jinxin Pei, Alaknanda Adwal, Philipp Reineck, Brant C. Gibson, Mark R. Hutchinson and Andrew D. Abell
Conference Name
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.
School/Discipline
Dissertation Note
Provenance
Description
Access Status
Rights
© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim