Nanoscale complexes of recombinant silk molecules containing THPs with DNA are designed as less cytotoxic and highly target‐specific gene carriers. Genetically engineered silk proteins containing poly(L ‐lysine) domains to interact with pDNA and the THP to bind to specific tumorigenic cells for target‐specific pDNA delivery are prepared, followed by in vitro transfection into MDA‐MB‐435 melanoma cells, highly metastatic human breast tumor MDA‐MB‐231 cells, and non‐tumorigenic MCF‐10A breast epithelial cells. The silk/poly(L ‐lysine) block copolymer containing Lyp1 (ML‐Lyp1) shows significant differences from silk/poly(L ‐lysine) block copolymer containing F3 (ML‐F3) in cytotoxicity to MCF10A cells. ML‐F3 is the most promising candidate for target delivery into tumorigenic cells.
