DNA Nanoclews for Stimuli-Responsive Anticancer Drug Delivery

The technique of rolling circle amplification (RCA) emerged recently as a robust tool to generate the regularly patterned DNA structures in addition to its long-recognized ability of amplifying biological signals. Here, we demonstrate the strategy of RCA-driven generation of nano-scaled cocoon-like DNA particles, designated as DNA nanoclews, for loading and delivering a small molecule anticancer drug. The characteristic biodegradability of DNA was harnessed to control the timing and location of drug release by utilizing a polymeric nanogel encapsulating DNA-degrading enzyme DNase I. This smart drug delivery system based on RCA amplicons could get internalized into targeted cells and release the cargo using the endosomal acidity as a trigger.