posted on 2021-07-14, 16:05authored byJia-Qi Fan, Yi-Jing Li, Zi-Jin Wei, Yu Fan, Xiang-Dan Li, Zi-Ming Chen, Da-Yong Hou, Wu-Yi Xiao, Meng-Ru Ding, Hao Wang, Lei Wang
Life
is recognized as a sophisticated self-assembling material
system. Cancer involves the overexpression and improper self-assembly
of proteins, such as cytoskeleton protein vimentin, an emerging target
related to tumor metastasis. Herein, we design a binding-induced fibrillogenesis
(BIF) peptide that in situ forms fibrous networks, blocking the improper
self-assembly of vimentin against cancer. The BIF peptide can bind
to vimentin and subsequently perform fibrillogenesis to form fibers
on vimentin. The resultant peptide fibrous network blocks vimentin
skeletonization and inhibits the migration and invasion of tumor cells.
In mouse models of tumor metastasis, the volume of tumor and the number
of lung metastases are markedly decreased. Moreover, the efficacy
of BIF peptide (5 mg/kg) is much higher than small molecular antimetastasis
drug withaferin A (5 mg/kg) as a standard, indicating that the BIF
peptide shows advantages over small molecular inhibitors in blocking
the intracellular protein self-assembly.