Targeted degradation of anaplastic lymphoma kinase by gold nanoparticle-based multi-headed proteolysis targeting chimeras

Proteolysis targeting chimeras (PROTACs) are molecules that comprise a ligand for binding a protein of interest (POI), a connecting linker and a ligand for recruiting E3 ligase, and cause degradation of the target POI. Here, the first multi-headed PROTAC, as a proof of concept, is developed as a gold nanoparticle (GNP)-based drug delivery system for delivering PROTACs to target ALK. Pegylated GNPs loaded with both ceritinib and pomalidomide molecules, termed Cer/Pom-PEG@GNPs, showed good stability in several media. The GNP conjugates potently decreased the levels of ALK fusion proteins in a dose- and time-dependent manner, and specifically inhibited the proliferation of NCI-H2228 cells. READ ARTICLE

Colloids and Surfaces B: Biointerfaces DOI: 10.1016/j.colsurfb.2020.110795

Authors: Yingming Wang, Lingfei Han, Fulei Liu, FubaiYang, Xueyang Jiang, Haopeng Sun, FengFeng, Jingwei Xue, Wenyuan Liu

Pre-ClinicalKirk SmithJanuary 13, 2020Multi-headed PROTAC, Target protein degradation, ALK, Gold nanoparticle, Drug delivery system.