An NRP1/MDM2‐Targeted D‐Peptide Supramolecular Nanomedicine for High‐Efficacy and Low‐Toxic Liver Cancer Therapy

Supramolecular nanomedicines based on self‐assembly of D‐peptides have been of great interest as potential candidates for cancer therapy. Neuropilin‐1 (NRP1) and mouse double minute 2 (MDM2) have been considered as the anticancer targets because of their overexpression in cancers. However, NRP1/MDM2‐targeted D‐peptide supramolecular nanomedicines remain unreported. Here, a potent anticancer D‐peptide supramolecular nanomedicine targeting NRP1 and MDM2, termed as NMTP‐5, is identified by using structure‐based virtual screening techniques. NMTP‐5 exhibits good biostability and strong cellular uptake performance. Moreover, NMTP‐5 displays strong anticancer activity to SK‐Hep‐1 cells in vitro and in vivo, with no apparent host toxicity. This work demonstrates that NMTP‐5 can be used as a potential chemotherapeutic agent for the treatment of liver cancer.