Integrated tissue and serum proteomics on magnet-guided photothermal therapy using Au/Fe/Au trilayer nanodiscs

Nanodiscs are emerging as promising nanomaterials for localized therapies as they enable magnetic targeting and near-infrared (NIR) laser–driven photothermal stimulation. In this study, we performed comprehensive proteomic analyses of both tissue and serum from mouse models to elucidate the effects of photothermal therapy using Au/Fe/Au trilayer nanodiscs (AuFeAuNDs) on both local and systemic protein regulation. Protein expression in tissue and serum was analyzed under six experimental exposure conditions: phosphate buffered saline (control, Ctrl), control with laser irradiation (Ctrl + L), gold–polyethylene glycol (PEG) nanodiscs with laser irradiation (Au), AuFeAuNDs without magnetic induction and with laser irradiation (MgX), AuFeAuNDs with magnetic induction and without laser irradiation (MgO − L), and AuFeAuNDs with magnetic induction and with laser irradiation (MgO + L). Tissue proteomes showed enrichment of proteins involved in histone modification and transcriptional regulation, while serum proteomes revealed alterations in immune responses and coagulation pathways, with the combined AuFeAuNDs, magnet, and laser treatment promoting fibrinolysis. Fifty-two shared proteins across tissues and serum were implicated in ferroptosis, coagulation, and defense responses. Overall, these findings provide mechanistic insights into the biological impact and biosafety of nanodisc-mediated photothermal therapy, as well as highlight potential biomarkers for monitoring therapeutic responses.