Strategies for Delivering Protein Drugs into the Cell Cytosol
HUANG Lin, SHI Yonghui, WU Junjun*
Protein drugs offer promising opportunities for treating complex diseases such as diabetes, cancer, and cardiovascular disorders, owing to their ability to selectively modulate intracellular biochemical processes and their superior biocompatibility and safety. However, the clinical utility of most protein drugs is limited by poor cell membrane permeability, because of their large molecular size and high hydrophilicity. This limits their targeting to extracellular sites and reduces the range of druggable targets. Additionally, the complex tertiary structure and unique biochemical properties of protein drugs make them highly vulnerable to external factors that can compromise their activity. These inherent limitations significantly constrain their application in disease treatment. Therefore, the development of efficient delivery systems to overcome these barriers is essential. Recently, several advanced delivery platforms capable of effectively transporting proteins into the cytoplasm have been developed, opening new avenues for both research and clinical applications. This review will introduce the recent developments in protein delivery systems based on different materials, such as those based on liposomes, peptide/protein nanocarriers, polymers, and inorganic, in the field of cytosolic delivery of protein drugs.
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