Dimeric PD-L1 specific affibody grafted Fe-based nanosheets for tumor-targeting dual-mode magnet resonance imaging and enhancement of Photothermal-Immunotherapy

Biodegradable Two-dimensional (2D) nanomaterials have attracted tremendous interest in biomedical application. Herein, a biodegradable ferrous sulfide nanosheet with ultrathin structure and uniform size was developed. Following its development, the application of the self-enhanced photothermal nanoplatform (FMPN) in vivo by combining Mn-DOTA and dimeric PD-L1 affibody for targeted dual-mode magnetic resonance imaging (MRI) guided synergistic tumor therapy is explored. Dual-contrast enhanced subtraction imaging (DESI) was used to evaluate the excellent T1-T2 MRI ability of FMPN. FMPN displayed excellent photothermal conversion efficiency (η = 40.33 %) and biodegradability, thus had good tumor photothermal therapy effects with good biosafety. In addition, FMPN with pH-responsive Fe 2+ release can effectively induce tumor cell ferroptosis, further intensifying PTT and subsequent immunologic cell death. PD-L1 affibody could endow this nanoplatform with efficient tumor targeting, terminating T cells’ immune suppression by effectively blocking the interaction between PD-1 and PD-L1. Systemic delivery of FMPN significantly inhibited tumor progression in primary, metastatic and abscopal tumors, and showed obvious dual-mode MRI enhancement. Therefore, this nanoplatform exhibited promising potential for MRI-guided synergistic ferroptosis/photothermal/immunotherapy.