Syphilis mimetic nanoparticles for cuproptosis-based synergistic cancer therapy via reprogramming copper metabolism

A syphilis mimetic TP0751-peptide decorated stem cell membrane-coated copper-based metal organic framework (Cu-MOF) nanodelivery platform was developed for the brain targeted delivery of small interfering RNA targeting copper-transporting protein ATP7a (siATP7a) in vivo. The bionic nanodelivery system holds a good biocompatibility, high BBB transcytosis, effective tumor accumulation, and specifically blocked copper trafficking, increased copper intake and triggered cuproptosis, improved therapeutic efficacy in SCLC brain metastasis tumor-bearing mice.