Nanocarrier of Pin1 inhibitor based on supercritical fluid technology inhibits cancer metastasis by blocking multiple signaling pathways  

作　　者：Fengzhu Zhang Aiwen Zhang Youning Xie Haiying Wen Ranjith Kumar Kankala Jing Huang Anjun Zhang Qi Wang Biaoqi Chen Haiyan Dong Zhao Guo Aizheng Chen Dayun Yang 

机构地区：[1]Fujian Key Laboratory of Translational Research in Cancer and Neurodegenerative Diseases,School of Basic Medical Sciences,Fujian Medical University,Fuzhou,350108,PR China [2]Institute of Biomaterials and Tissue Engineering,Huaqiao University,Xiamen,361021,PR China [3]Fujian Provincial Key Laboratory of Biochemical Technology(Huaqiao University),Xiamen,361021,PR China

出　　处：《Regenerative Biomaterials》2023年第1期574-589,共16页再生生物材料（英文版）

基　　金：supported by the National Natural Science Foundation of China(Grant Number 81502115);Fujian Provincial Natural Science Foundation(Grant Numbers 2021J01671,2017J01529);the Joint Funds for the Innovation of Science and Technology,Fujian Province(Grant Number 2016Y9041).

摘　　要：Cancer metastasis is the primary cause of all cancer-related deaths due to the lack of effective targeted drugs that simultaneously block multiple signaling pathways that drive the dissemination and growth of cancer cells.The unique proline isomerase Pin1 activates numerous cancer pathways,but its role in cancer metastasis and the inhibitory efficacy of Pin1 inhibitors on cancer metastasis are unknown.Moreover,the applicability of Pin1 inhibitor-all-trans retinoic acid(ATRA)is limited due to its several drawbacks.Herein,uniform ATRA-loaded polylactic acid-polyethylene glycol block copolymer nanoparticles(ATRA-NPs)with high encapsulation efficiency,good cellular uptake,excellent controlled release performance and pharmacokinetics are developed using supercritical carbon dioxide processing combined with an optimized design.ATRA-NPs exhibited excellent biosafety and significant inhibition on the growth and metastasis of hepatocellular carcinoma.Pin1 played a key role in cancer metastasis and was the main target of ATRA-NPs.ATRA-NPs exerted their potent anti-metastatic effect by inhibiting Pin1 and then simultaneously blocking multiple signaling pathways and cancer epithelial-mesenchymal progression.Since ATRA-NPs could effectively couple the inhibition of cancer cell dissemination with cancer growth,it provided a novel therapeutic strategy for efficiently inhibiting cancer metastasis.

关 键 词：cancer metastasis targeted therapy Pin1 inhibitor nano delivery signaling pathway 

分 类 号：R730.5[医药卫生—肿瘤] R318[医药卫生—临床医学] TB383[一般工业技术—材料科学与工程]