RRC ID 73470
Author Zhang A, Abdellatef SA, Nakanishi J.
Title Mechanistic investigation into selective cytotoxic activities of gold nanoparticles functionalized with epidermal growth factor variants.
Journal Anal Sci
Abstract Epidermal growth factor (EGF) gains unique selective cytotoxicity against cancer cells upon conjugation with gold nanoparticles (GNPs). We have previously developed several lysine-free EGF mutants for favorable interactions between the nanoparticle conjugates with EGF receptor (EGFR) and found one mutant (SR: K28S/K48R) showing stronger anticancer activities. However, the exact mechanisms for the selective cytotoxicity enhancement in the SR mutant remained unsolved. In this study, we analyzed how the nanoparticle conjugates of EGF variants interacted differently with A431 cancer cells, in terms of receptor binding, activation, and trafficking. Our results indicate that the essential feature of the SR-GNP conjugates in the cytotoxicity enhancement is their preferential activation of the clathrin-independent endocytosis pathway. It is suggested that we should focus on not only ligand-receptor binding affinity but also the selectivity of the receptor endocytic route to optimize the anticancer effects in this modality.
Published 2023-1-14
DOI 10.1007/s44211-022-00256-7
PII 10.1007/s44211-022-00256-7
PMID 36639559
Human and Animal Cells A431(RCB0202)