Precision Spherical Nucleic Acids Enable Sensitive FEN1 Imaging and Controllable Drug Delivery for Cancer-Specific Therapy.

Accurate diagnosis and targeted therapy are essential to precision theranostics. However, nonspecific response of theranostic agents in healthy tissues impedes their practical applications. Here, we design an activatable DNA nanosphere for specifically in situ sensing of cancer biomarker flap endonuclease 1 (FEN1) and spatiotemporally modulating drug release. The gold nanostar-conjugated FEN1 substrate acts as spherical nucleic acid and induces a fluorescence signal upon a FEN1 stimulus for diagnosis. Guided by the nanoflare, external NIR light then triggers a controlled release of carried drugs at desired sites. This DNA nanosphere not only exhibits good stability, sensitivity, and specificity toward FEN1 assay but also serves as a precision theranostic agent for targeted and controlled drug delivery. Our study provides a reliable method for FEN1 imaging in vitro and in vivo and suggests a powerful strategy for precision medicine.