Peptide nanoplexes are a promising, modular drug delivery platform that can enable enhanced tumor accumulation of a wide range of therapeutics including small molecules, siRNA, plasmid DNA, and mRNA.5, 15, 46, 47 Here, we show that a novel polymer blend architecture consisting of three NCA peptide homologs can self‐assemble to form stable siRNA nanoplexes that silence a key DNA‐damage response pathway in p53‐deficient advanced ovarian tumors. This evidence concerns the gene TP53 and ovarian neoplasm.