Nanomotor‐Driven Targeting Chimeras as Accelerators for the Degradation of Extracellular Proteins
Year: 2024
Type: article
Abstract: Targeted protein degradation (TPD) is emerging as a therapeutic paradigm and a serviceable research tool in chemical biology and disease treatment. However, without driving sources, most targeting chimeras (TACs) lack the capability of self‐diffusion and active searching in biological environments, which significantly impedes degradation efficiency. Herein, nanomotor‐driven targeting chimeras (MotorTACs) are ingeniously designed to achieve effective internalization and degradation of extracellular platelet‐derived growth factor (PDGF), a driver to cancer invasion and metastasis. Catalyzed by endogenous H 2 O 2 , MotorTACs diffused rapidly and searched actively in living cells, as visualized at the single‐particle level under the dark‐field mode. Hydrolysis efficiency is significantly enhanced as target protein degradation is complete in only 4 h. Furthermore, MotorTACs‐mediated degradation of PDGF is found to be via the lysosome and ubiquitin‐proteasome dual‐degradation pathways. Taking advantage of the properties, it is anticipated that MotorTACs provide a unique strategy against extracellular undruggable proteins, thus advancing the development of therapeutic interventions in chemical biology and disease treatment.
Source: Small
Institutions: Fudan University, Shanghai Stomatological Hospital
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: bronze
Award: G7017843709
OpenAlex ID: W4402520451