4178898 - Multifunctional polypeptide nanocomposites to unify ferroptosis, nitric oxide and photothermia for amplifying antitumor immunity

Tumor metastasis and relapse mainly results in therapy failure and becomes a big challenge in oncology. Immunogenic cell death (ICD) of tumors mediated immunotherapy (IT) is attracting widely for solving that problem although achieving sufficient ICD and strong immune response is challenging for nanoparticles-based cancer IT1,2. Herein we construct a multifunctional polypeptide coordinate nanocomposite that possesses near infrared photothermia (PT) and responsive releases of nitric oxide (NO) and iron ions, which synergistically killed cancer cells and highly prohibited metastatic 4T1 cells invasion and migration by PT-boosted NO release and ferroptosis (FT)3. Remarkably, triple FT-NO-PT treatment amplify the ICD effects and outperform combo/monotherapy FT-PT and FT in cancer cells and tumors, which further activated dendritic cells (DCs) maturation, and primed CD4+T and CD8+T cells immune responses and memory effects, playing four birds with one stone (i.e., FT-NO-PT-IT).