Alpha Fetoprotein Delivered Drugs Targeting Therapy of Cancer / 中国生物化学与分子生物学报

ABSTRACT

Alpha fetoprotein (AFP) is a highly expressed protein during fetal development. It’ s a shuttle protein that transports nutrients to embryonic cells. Similarly, during the development of malignant tumors such as liver cancer, tumor cells also express high levels of AFP and its receptors. They uptake AFP and its delivered substances through AFP receptors. Therefore, AFP can be combined with anticancer drugs to attack tumor cells selectively. There are several ways of AFP to deliver drugs, which can be noncovalently bound with drugs, and the drugs are wrapped in the hydrophobic pocket of AFP; they can also combine with drugs through covalent bonds, or use AFP to connect with nanoparticles and liposomes to improve the effect of drug delivery. AFP delivered drugs can be effectively released in the low pH environment of cancer cells. In order to avoid the risk of AFP carcinogenesis, drugs can be delivered by modifying AFP or using AFP fragments. Because AFP delivered drugs targeting therapy mainly attacks cancer cells that expressed AFP receptor, it has little effect on normal cells. AFP delivred drugs can not only promote the absorption of drugs by tumor cells, enhance the anti-cancer activity of drugs, but also overcome the problem of multidrug resistance (MDR). In addition, studies have found that AFP delivered drugs also have the effect of immunotherapy. AFP delivered drugs can not only activate T cell receptors, eliminate immune tolerance and inhibit tumor growth, but also inhibit myeloid derived suppressor cells (MDSCs), activate NK cells and T cells, thus destroying cancer cells and preventing cancer stem cell metastasis. Therefore, AFP delivery of drug is a new therapy combining immunotherapy and targeted chemotherapy, and it may become a strategy for cancer treatment in the future.