Modulation of Angiogenic Activity by Light-Activatable miRNA-Loaded Nanocarriers

The combinatorial delivery of miRNAs holds great promise to modulate cell activity in the context of angiogenesis. Yet, the delivery of multiple miRNAs with spatiotemporal control remains elusive. Here, we report a plasmonic nanocarrier to control the release of two microRNAs. The nanocarrier consists of gold nanorods modified with single-stranded DNA for hybridization with complementary DNA-conjugated microRNAs. DNA strands with distinct melting temperatures enable the independent release of each microRNA with a near-infrared laser using the same wavelength but different powers. Tests in human outgrowth endothelial cells (OECs) indicate that this system can be used to silence different targets sequentially and, by doing so, to modulate cell activity with spatiotemporal resolution. Finally, using an in vivo acute wound healing animal model, it is demonstrated that the order by which each miRNA was released in transplanted OECs significantly impacted the wound healing kinetics.