MicroRNAs are small noncoding RNAs that function as powerful endogenous regulators of gene expression. Dysregulation of MicroRNA biogenesis has been correlated with the onset and progression of many human diseases. MicroRNA therapy involves the re-equilibration of aberrant intracellular MicroRNA expression profiles for long-term disease management. Despite the significant potential of MicroRNA therapy, the utilization of MicroRNA-based therapeutics has been drastically hindered in practice by the lack of a targeted and translatable delivery vehicle. CD44 is a cell surface glycoprotein that facilitates cellular communication and motility through cell-cell and cell-extracellular matrix interactions. CD44 has been shown to be elevated in multiple disease states including cancer making it a potential diagnostic biomarker and an ideal receptor for targeted drug delivery systems. We describe a method for targeting CD44 using a lipid nanocarrier for the cytoplasmic delivery of active MicroRNA.