Advances on Tumor-Targeting Delivery of Cytotoxic Proteins

Great attention has been paid to cytotoxic proteins (e.g., ribosome-inactivating proteins, RIPs) possessing high anticancer activities; unlike small drugs, cytotoxic proteins can effectively retain inside the cells and avoid drug efflux mediated by multidrug resistance transporters due to the large-size effect. However, the clinical translation of these proteins is severely limited because of various biobarriers that hamper their effective delivery to tumor cells. Hence, in order to overcome these barriers, many smart drug delivery systems (DDS) have been developed. In this review, we will introduce two representative type I RIPs, trichosanthin (TCS) and gelonin (Gel), and overview the major biobarriers for protein-based cancer therapy. Finally, we outline advances on the development of smart DDS for effective delivery of these cytotoxic proteins for various applications in cancer treatment.