4.8 Article

Activatable and Cell-Penetrable Multiplex FRET Nanosensor for Profiling MT1-MMP Activity in Single Cancer Cells

Journal

NANO LETTERS
Volume 15, Issue 8, Pages 5025-5032

Publisher

AMER CHEMICAL SOC
DOI: 10.1021/acs.nanolett.5b01047

Keywords

activatable cell-penetrating peptide; multiplex signals; FRET nanosensor; MT1-MMP; single cell; cancer

Funding

  1. NIH [HL098472, HL109142, HL121365, R00CA153914]
  2. NSF [CBET1360341, DMS1361421]
  3. UC San Diego, Beckman Laser Institute, Inc.
  4. NSF Singapore through the Singapore MIT Alliance for Research and Technology's BioSystems and Micromechanics Inter-Disciplinary Research programme
  5. National Cancer Institute [1R33CA174550]

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We developed a quantum-dot-based fluorescence resonance energy transfer (QD-FRET) nanosensor to visualize the activity of matrix metalloproteinase (MT1-MMP) at cell membrane. A bended peptide with multiple motifs was engineered to position the FRET pair at a close proximity to allow energy transfer, which can be cleaved by active MT1-MMP to result in FRET changes and the exposure of cell penetrating sequence. Via FRET and penetrated QD signals, the nanosensor can profile cancer cells.

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