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.
Chemotherapeutic treatment of cancers is a challenging endeavor, hindered by poor selectivity towards tumorous tissues over healthy ones. Preferentially delivering a given drug to tumor sites necessitates the use of targeting elements, of which there are a wide range in development. In this Review, we highlight recent examples of peptide-based targeting ligands that have been exploited to selectively deliver a chemotherapeutic payload to specific tumor-associated sites such as the vasculature, lymphatics, or cell surface. The advantages and limitations of such approaches will be discussed with a view to potential future development. Additionally, we will also examine how peptide-based ligands can be used diagnostically in the detection and characterization of cancers through their incorporation into imaging agents.
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