Multi-Functional Peptide-MicroRNA Nanocomplex for Targeted MicroRNA Delivery and Function Imaging

Targeted delivery of microRNA (miRNA) mimics into specific cells/tissues and real-time monitoring on the biological function of delivered miRNA mimics at molecular level represent two major challenges in the development of miRNA-based therapeutics. Here we report a highly efficient method to address these two challenges simultaneously by using the self-assembled nanocomplex formed by miRNA mimics with a multi-functional peptide conjugate. Using the nanocomplex formed by tumor-suppressive miR-34a and the multi-functional peptide conjugate FA-R9-FPcas3, we demonstrated the highly efficient and target-selective delivery of miR-34a into HeLa cells and tumors. With the activatable fluorescence probe integrated in the peptide conjugate FA-R9-FPcas3, the intracellular function of miR-34a delivered by the nanocomplex to upregulate active Caspase-3 was imaged in real-time. The nanocomplex also showed significant therapeutic effects to induce apoptosis in HeLa cells and to suppress tumor growth upon tail vein injection into living mice bearing subcutaneous HeLa tumors.