Research team of Zhan Changyou from Fudan University has made new progress in the design of brain targeted liposomes

Recently, the team of Zhan Changyou, Fudan University, designed a novel brain targeted liposome drug, which can accurately "catch" endogenous apolipoproteins and maintain their biological activity during blood circulation, so as to achieve efficient brain targeted drug delivery The related achievements were published online in nature communications (DOI: 10.1038 / s41467-019-11593-z) under the title of brain targeted drug delivery by controlling protein corona functions Liposome is one of the most widely used nano drug carriers Targeted liposome drug is to modify functional molecules (such as small molecules, polypeptides and antibodies) on the surface of liposome in order to break through the physiological barriers (such as blood-brain barrier, blood-eye barrier and biofilm barrier) in the process of drug delivery, so as to achieve the accumulation of drugs at the target site, so as to improve the efficacy and reduce the side effects In the past 40 years, the research of targeted liposome drugs has been very active, but it has not yet achieved clinical transformation More and more studies have found that in vivo delivery process, plasma protein adsorbs on the surface of targeted liposome drugs to form protein crown, which greatly affects the biological activity of targeted molecules, may affect the biological distribution of drugs, and aggravate toxic and side effects For example, zhanchangyou team found that the natural immunoglobulin IgM is easy to be adsorbed on the surface of brain targeted long peptide modified liposome drug, which leads to short blood circulation time, increased liver and spleen accumulation and strong immunogenicity (nature communications 2018, 9, 2982; molecular pharmaceuticals 2019, 16, 907) The clinical transformation of targeted liposome drugs needs to be adjusted from the source design There are many kinds of apolipoproteins in plasma that can cross the blood-brain barrier One of the mechanisms of clearing a β protein in the brain is to combine the lipid binding areas of various apolipoproteins (such as apoE, ApoA1 and APOJ), expose the receptor binding areas at the same time, and transport them to the peripheral through the corresponding receptors on the blood-brain barrier Because the related receptors can transport in two directions, they can also transport the peripheral ligands to the brain After being modified on the surface of liposome, the a β protein was designed to obtain a non-toxic peptide, which could actively adsorb the lipid binding area of the target apolipoprotein during the blood circulation process, and at the same time, the receptor binding area was exposed on the surface of liposome to play an efficient brain targeting role After the target short peptide modified liposome was loaded with adriamycin, a variety of brain tumors in situ (gliomas and medulloblastomas) were successfully treated, which significantly prolonged the median survival time of the model mice The brain targeted delivery strategy breaks through the traditional design idea, actively uses the functional protein in the plasma, overcomes many defects of the traditional brain targeted liposome drugs, and has high safety, and has good clinical transformation prospects The relevant research results have applied for PCT international patent The delivery strategy has similar functions in human blood and can be applied to nano delivery systems other than liposomes Zhang Zui is the first author of the paper, and Zhan Changyou is the corresponding author The research was supported by the Central Organization Department, the National Natural Science Foundation of China, the Shanghai Municipal Science and Technology Commission, the Education Commission and the Health Commission, as well as the State Key Laboratory of polymer molecular engineering of Fudan University.