Figure 2.

Graphical depictions highlighting the varied miRNA delivery platforms developed for cancer therapeutics, as well as their mechanisms of cellular internalization. Schematic diagram illustrating the generalized modes of cell entry for both viral and nonviral miRNA delivery systems. To cross the plasma membrane of the targeted cell, many of the delivery systems utilize multiple different cellular entry routes, but in general, utilize either direct cellular entry mechanisms or endocytosis-based uptake pathways [70,71]. For example, viral vectors, such as adenovirus (AV), adeno-associated virus (AAV), and lentivirus (LV), can utilize either direct entry mechanisms or endocytosis-based uptake pathways in their delivery of miRNA mimic-encoded RNA/DNA cargo into cells. Other examples, in terms of nonviral delivery systems, can include direct cytoplasmic entry via lipid fusion of a lipid-based vector with the plasma membrane or direct cellular entry of a polymer (e.g., polyamidoamine (PAMAM))-based vector in the delivery of antagomiR cargo. Additionally depicted are examples of cellular internalizations via endocytosis of inorganic (e.g. gold (Au)), extracellular vesicle (EV), and peptide-based vectors in complex with miRNA mimic cargo. Select images within the figure were acquired from BioRender.com.