Aminofullerenes as targeted inhibitors of EGFR: from pancreatic cancer inhibitors to Drosophila m . Toxicology

Pancreatic ductal adenocarcinoma (PDAC) is recognized as one of the most formidable cancers, largely due to its distinct microenvironment characterized predominantly by extensive desmoplastic stroma. In this study, we synthesized three novel water-soluble fullerene-based nanomaterials targeting EGFR protein. The direct amination of fullerene carbon atoms, was followed by conjugation with a modified derivative of the EGFR inhibitor-erlotinib, resulting in the formation of novel water-soluble fullerene derivatives. Further investigation into PAN02 and AsPC-1 cell lines revealed that these fullerene nanomaterials could induce cell cycle arrest in the G0/G1 phase, corroborated by alterations in the expression levels of the p27 and cyclin E1 proteins. Additionally, mechanisms of cell death were identified as autophagy for C60BUT and C70BUT-ERL, and apoptosis for Gd@C82EDA-ERL nanomaterials. Crucially, the study uncovered the efficacy of synthesized aminofullerenes in inhibiting the EGFR signaling pathway. The further toxicological studies of Gd@C82EDA-ERL fullerene on Drosophila melanogaster, underscored its potential for theranostic applications.