The cytosolic delivery of therapeutic proteins represents a promising strategy for addressing diseases caused by protein dysfunction. Despite significant advances, efficient delivery remains challenging due to barriers such as cell membrane impermeability, endosomal sequestration, and protein instability. This review summarizes recent progress in protein delivery systems, including physical, chemical, and biological approaches, with a particular focus on strategies that enhance endosomal escape and targeting specificity. We further discuss the clinical translatability of these approaches and propose future directions for improving delivery efficiency and safety, ultimately unlocking the therapeutic potential of intracellular proteins.
Keywords: Cytoplasmic delivery; Endosomal escape; Protein delivery vectors; Protein drugs; Targeted delivery.