Protein therapeutics holds significant promise for improving human health. Our organism contains thousands of proteins, which perform essential functions in growth, development and metabolism regulation. Many diseases arise from the alterations in the functions of intracellular proteins. Therefore, the administration of therapeutic proteins has shown great potential in the treatment of many diseases, including cancer and diabetes. Protein therapeutics has emerged since the 1980s and represents currently a significant part of biopharmaceuticals. For example, Lantusî, an engineered protein (insulin) was one of the top ten selling biopharmaceuticals in 2009. Moreover, protein drugs with much better therapeutic performance are developed every year. The pharmaceutical research and manufacturers of America (PHRMA) listed 78 therapeutic proteins in 813 new biotechnology medicines related to more than 100 diseases in 2011, including virus infectious, cancer and autoimmune diseases. The high intracellular activity and specificity of proteins compared to more conventional, low molecular weight drugs often allows for a better treatment of diseases. Moreover, protein drugs may be safer than gene therapy because no random or permanent genetic changes are involved. Despite their potential medical applications, effective delivery of the proteins to a target site remains a challenge due to rapid clearance from the body. To achieve effective intracellular protein release, delivery platforms that overcome various biological barriers - from the system level, to the organ level, to the cellular level ââ¬â are needed. For example, the protein delivery carrier in the bloodstream needs to avoid kidney filtration, uptake by phagocytes, aggregation with serum proteins, and degradation by endogenous nucleases. Also, the delivery vehicle needs to transport the protein from the bloodstream through the vascular endothelial barriers. Moreover, once the carrier has been uptaken by the targeted cell, it must escape during early stages of the endolysosomal pathway, to avoid degradation by low pH and various hydrolytic enzymes in the lysosomes. Therefore, the clinical success of many therapeutic proteins is intimately dependent on the development of safe and efficient targeted protein delivery technologies. [Vivero-Escoto JL (2013) Nanovehicles for Intracellular Protein Delivery]
Last date updated on September, 2024
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