Enzyme-specific doxorubicin drug beacon as drug-resistant theranostic molecular probes

Lye Lin Lock; Zidu Tang; Daniel Keith; Claudia Reyes; Honggang Cui

doi:10.1021/acsmacrolett.5b00170

Enzyme-specific doxorubicin drug beacon as drug-resistant theranostic molecular probes

Lye Lin Lock, Zidu Tang, Daniel Keith, Claudia Reyes, Honggang Cui

Whiting School of Engineering

Research output: Contribution to journal › Article › peer-review

Abstract

We report here on the use of anticancer drug doxorubicin (Dox) to construct a Förster 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.

Original language	English (US)
Pages (from-to)	552-555
Number of pages	4
Journal	ACS Macro Letters
Volume	4
Issue number	5
DOIs	https://doi.org/10.1021/acsmacrolett.5b00170
State	Published - May 19 2015

ASJC Scopus subject areas

Organic Chemistry
Polymers and Plastics
Inorganic Chemistry
Materials Chemistry

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10.1021/acsmacrolett.5b00170

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title = "Enzyme-specific doxorubicin drug beacon as drug-resistant theranostic molecular probes",

abstract = "We report here on the use of anticancer drug doxorubicin (Dox) to construct a F{\"o}rster 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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AU - Lock, Lye Lin

AU - Tang, Zidu

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AU - Reyes, Claudia

AU - Cui, Honggang

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Enzyme-specific doxorubicin drug beacon as drug-resistant theranostic molecular probes

Abstract

ASJC Scopus subject areas

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