Figure 3.
Schematic presentation of Combination therapy of ligand protein and miRNA using nanoliposomes for NSCLC and MPM over-expressing EphA2. A. The ligand proteins, ephrin-A1, were conjugated with miR-Let-7a encapsulated nanoliposomes via the reaction between amines on proteins and cyanuric chlorides on PEGylated lipids. The ephrin-A1, ligand of EphA2 receptor acts as targeting and therapeutic agents in the complex system. B. The miR-Let-7a/liposome/ephrinA1 complex system suppresses tumor growth through ephrin-A1/EphA2 binding and intracellular release of miR-Let-7a. The binding of ephrin-A1 leads to phosphorylation of EphA2 and inhibits the RAS pathway. In one of the signaling pathways, the activation of EphA2 induces miR-Let-7a which inhibits RAS signaling. Combined with ligand proteins, the extrinsic miR-Let-7a were delivered intracellularly majorly through endocytosis of nanoliposomes to enhance therapeutic effectiveness. BBS= borate buffered saline; TK= tyrosine kinase domain; PDZ= PDZ-binding motif; P= phosphorylation; ┴= inhibition [1-3].