Journal
ACS MACRO LETTERS
Volume 4, Issue 5, Pages 552-555Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsmacrolett.5b00170
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Funding
- National Science Foundation [DMR 1255281]
- W.W. Smith Charitable Trust
- Division Of Materials Research
- Direct For Mathematical & Physical Scien [1255281] Funding Source: National Science Foundation
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We report here on the use of anticancer drug doxorubicin (Dox) to construct a Forster resonance energy transfer (FRET)-based theranostic molecular probe by covalently linking together through a lysine junction a fluorescent drug, a black hole quencher, and a cell-penetrating peptide. We show that upon cleavage by the target lysosomal protease cathepsin B (CatB) the designed drug beacon could release the fluorescent drug serving as an indicator for CatB. Our cell studies suggest that the drug-beacon design can help to circumvent the Dox drug resistance in NCI/ADR-Res ovarian cancer cells, showing significant improvement in cell cytotoxicity compared to the free drug. We believe our design opens up new opportunities to exploit the new functional and structural features of anticancer drugs in addition to their characteristic cytotoxicity.
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