Raman Imaging of Targeted Drug Delivery with DNA‐Based Nano‐Optical Devices

Raman spectroscopy (RS) has emerged as a novel optical imaging modality by identifying molecular species through their bond vibrations, offering high specificity and sensitivity in molecule detection. However, its application in intracellular molecular probing has been limited due to challenges in combining vibrational tags with functional probes. DNA nanostructures, known for their high programmability, have been instrumental in fields like biomedicine and nanofabrication. So far, their ability to customize Raman signals remains largely untapped. In this study, a new class of Raman active DNA origami-based hybrid nanodevice (ND) for targeted cancer cell drug delivery and imaging is engineered. The ND is specifically engineered for metastatic prostate cancer treatment, featuring a legumain enzyme-responsive sequence for the controlled release of the chemotherapeutic agent doxorubicin. Integrating RS with precise targeting, the ND enables imaging of aggressive cancer cells and efficient drug delivery with minimal off-target effects. The developed device offers stimuli-responsive behavior, enhanced stability, exceptional tunability, and potent targeting abilities, positioning it as a highly promising strategy for advancing precision cancer imaging and therapy.