Photocontrolled Delivery of miRNA34a Mimics Drive Apoptosis of Esophageal Cancer Cells and Regression of Tumors In Vivo

Abstract: Although rising evidence suggests the importance of microRNAs (miRNAs) in modulating tumorigenesis, cancer cell survival, and metastasis, the safe and effective delivery of miRNAs in vivo has remained a major challenge. Numerous approaches have been explored to modulate miRNA function by delivering exogenous miRNA mimics or miRNA inhibitors, including nanoscale vehicles such as viruslike particles, polymeric dendrimers, and liposomes. While these nanoparticles can suppress tumor growth in a variety of xenograft cancer models, none of these techniques achieve localized miRNA delivery with precise spatiotemporal control. This is a significant concern as offtarget gene silencing can result in severe side effects. To overcome these limitations with common nucleic acid delivery systems, we have developed a biocompatible, lightinducible nanoparticle system for delivering functional miRNA mimics to selectively induce cancer cell apoptosis, validated through in vitro experiments and in a human xenograft tumor model in vivo.


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