New progress has been made in the study of the mechanism of iron protein carrier

Recently, the
Institute of Biophysics of China/China
Nanoenzyme Engineering Laboratory Yan Xiyun
team published the latest research results on the drug loading method of Ferritin Drug Carrier online in the journal Nano Today, which revealed the presence of drug channels on the surface of ferritin drug vectors, laying the theoretical foundation for the clinical transformation of ferritin drugs.
is a naturally present iron-storage protein in human cells and plays a key role in iron balance and cell antioxidants in the human body. Ferrine has a unique shell core structure with a shell diameter of 12nm, which is self-assembled from 24 protein sub-base, and an inner cavity diameter of 8nm that can be loaded with therapeutic drugs. In the early stages of their work, the team found that human heavy-chain ferrrotein identifies tumor-marker molecular transirin proteins (TfR1) (Nat. Nanotechnol., 2012), which in turn gave ferritin a new drug carrier function (PNAS, 2014) and proposed a new concept of ferritin drug carrier (FDC) (J. Control. Release, 2019)。 FDC is similar to antibody-coupled drugs (ADCs), which target loaded small molecule drugs to tumor tissue through their receptor-specific recognition capabilities, but has advantages over ADC in terms of properties such as drug loading capacity, thermal stability, and susceptibility. However, the carrier of FDC has not been clear before.1. The "on-off" of the iron protein drug loading channel is regulated by temperature.
the
team conducted a study on the correlation between mutant design and drug carrying through the crystal structure analysis of ferroprotein, and found that the drug entered the inner cavity of ferrine through a specific channel. The channel consists of bits 89-92 and nearby amino acid residues and is located in a flexible area at the secondary symmetrical axis of the iron protein surface. Interestingly, the "switch" of the drug loading channel is temperature-regulated (Figure 1). The increase in ambient temperature helps the 89-92-bit amino acid residue swing away from the two axes, where the channel "opens" and the drug enters the ferrine cavity. Based on this finding, the researchers loaded ammoxin drugs into the ferrine cavity through temperature regulation. The results of animal experiments show that the iron protein drug has high stability, good safety and excellent anti-tumor effect. Moreover, the drug channel is universal for small molecule drugs, and the channel can also be loaded with cisplatin, oxalipari platinum, tableamycin and other small molecule drugs, with the potential to develop into a new drug technology platform.
China
Institute of Biophysics Yan Xiyun
and Researcher Fan Kelong are co-authors of this paper, Dr. Jiang Bing of Zhengzhou University School of Basic Medicine and Dr. Chen Xuexuan of china
Institute of Biophysics are co
-authors of this paper. (Source: Institute of Biophysics, Chinese Academy
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