1 research outputs found
Cell Membrane-Anchored DNA Nanoinhibitor for Inhibition of Receptor Tyrosine Kinase Signaling Pathways via Steric Hindrance and Lysosome-Induced Protein Degradation
Receptor tyrosine kinase (RTK) plays a crucial role in
cancer progression,
and it has been identified as a key drug target for cancer targeted
therapy. Although traditional RTK-targeting drugs are effective, there
are some limitations that potentially hinder the further development
of RTK-targeting drugs. Therefore, it is urgently needed to develop
novel, simple, and general RTK-targeting inhibitors with a new mechanism
of action for cancer targeted therapy. Here, a cell membrane-anchored
RTK-targeting DNA nanoinhibitor is developed to inhibit RTK function.
By using a DNA tetrahedron as a framework, RTK-specific aptamers as
the recognition elements, and cholesterol as anchoring molecules,
this DNA nanoinhibitor could rapidly anchor on the cell membrane and
specifically bind to RTK. Compared with traditional RTK-targeting
inhibitors, this DNA nanoinhibitor does not need to bind at a limited
domain on RTK, which increases the possibilities of developing RTK
inhibitors. With the cellular-mesenchymal to epithelial transition
factor (c-Met) as a target RTK, the DNA nanoinhibitor can not only
induce steric hindrance effects to inhibit c-Met activation but also
reduce the c-Met level via lysosome-mediated protein degradation and
thus inhibition of c-Met signaling pathways and related cell behaviors.
Moreover, the DNA nanoinhibitor is feasible for other RTKs by just
replacing aptamers. This work may provide a novel, simple, and general
RTK-targeting nanoinhibitor and possess great value in RTK-targeted
cancer therapy