4.8 Article

A therapeutic keypad lock decoded in drug resistant cancer cells

Journal

CHEMICAL SCIENCE
Volume 12, Issue 28, Pages 9754-9758

Publisher

ROYAL SOC CHEMISTRY
DOI: 10.1039/d1sc02521j

Keywords

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Funding

  1. European Cooperation in Science and Technology (COST) [17104]
  2. Scientific and Technological Research Council of Turkey [118Z668]

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A molecular keypad lock with photodynamic activity when exposed to GSH, esterase, and light in sequence is fabricated and effectively kills drug resistant MCF7 cancer cells. This work demonstrates the first biological application of small molecular keypad locks.
A molecular keypad lock that displays photodynamic activity when exposed to glutathione (GSH), esterase and light in the given order, is fabricated and its efficacy in drug resistant MCF7 cancer cells is investigated. The first two inputs are common drug resistant tumor markers. GSH reacts with the agent and shifts the absorption wavelength. Esterase separates the quencher from the structure, further activating the agent. After these sequential exposures, the molecular keypad lock is exposed to light and produces cytotoxic singlet oxygen. Among many possible combinations, only one 'key' can activate the agent, and initiate a photodynamic response. Paclitaxel resistant MCF7 cells are selectively killed. This work presents the first ever biological application of small molecular keypad locks.

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