Quantum Dot−Aptamer Conjugates for Synchronous Cancer Imaging, Therapy, and Sensing of Drug Delivery Based on Bi-Fluorescence Resonance Energy Transfer

TLDR

The authors develop a quantum‑dot–aptamer–doxorubicin conjugate that functions as a targeted imaging, therapeutic, and sensing platform for prostate cancer. The conjugate is built by attaching the PSMA‑recognizing A10 RNA aptamer to fluorescent quantum dots, intercalating doxorubicin into the aptamer stem to create a reversible self‑quenching Bi‑FRET system that both delivers the drug to PSMA‑positive cells and activates quantum‑dot fluorescence upon release. In vitro experiments show the conjugate specifically and sensitively images, treats, and reports drug delivery to prostate cancer cells.

Abstract

We report a novel quantum dot (QD)−aptamer(Apt)−doxorubicin (Dox) conjugate [QD−Apt(Dox)] as a targeted cancer imaging, therapy, and sensing system. By functionalizing the surface of fluorescent QD with the A10 RNA aptamer, which recognizes the extracellular domain of the prostate specific membrane antigen (PSMA), we developed a targeted QD imaging system (QD−Apt) that is capable of differential uptake and imaging of prostate cancer cells that express the PSMA protein. The intercalation of Dox, a widely used antineoplastic anthracycline drug with fluorescent properties, in the double-stranded stem of the A10 aptamer results in a targeted QD−Apt(Dox) conjugate with reversible self-quenching properties based on a Bi-FRET mechanism. A donor−acceptor model fluorescence resonance energy transfer (FRET) between QD and Dox and a donor−quencher model FRET between Dox and aptamer result when Dox intercalated within the A10 aptamer. This simple multifunctional nanoparticle system can deliver Dox to the targeted prostate cancer cells and sense the delivery of Dox by activating the fluorescence of QD, which concurrently images the cancer cells. We demonstrate the specificity and sensitivity of this nanoparticle conjugate as a cancer imaging, therapy and sensing system in vitro.