Tumor-targeted miRNA nanomedicine for overcoming challenges in immunity and therapeutic resistance

miRNA are critical messengers in the tumor microenvironment (TME) that influence various processes leading to immune suppression, tumor progression, metastasis and resistance. Strategies to modulate miRNAs in the TME have important implications in overcoming these challenges. However, miR delivery to specific cells in the TME has been challenging. This review discusses nanomedicine strategies to achieve cell-specific delivery of miRNAs. The key goal of delivery is to activate the tumor immune landscape as well as to prevent chemotherapy resistance. Specifically, the use of hyaluronic acid-based nanoparticle miRNA delivery to the TME is discussed. The discussion is focused on miRNA-125b for reprogramming tumor-associated macrophages to overcome immunosuppression and miRNA-let-7b to overcome resistance to anticancer chemotherapeutics because both these miRNAs have been extensively evaluated for delivery with hyaluronic acid-based delivery systems. miRNAs are the messenger molecules with the tumor that have significant influence on the cancer growth and progression. Many strategies have been evaluated to modulate these messengers artificially to obstruct cancer growth and destroy cancer cells. This review discusses one such strategy to deliver these messenger miRNAs using hyaluronic acid-based nanoparticles that harness the body's own immune system to fight cancer. The two miRNAs that this review discusses are miRNA-125b and miRNA-let7b.