Peptide‐Modified Dendrimer Nanoparticles for Targeted Therapy of Colorectal Cancer

Abstract Peptides have recently emerged as a promising class of targeting ligands for specific drug delivery in cancer treatment, which avoid undesirable side effects of the systemic administration of chemotherapeutics. Their conjugation with nanoparticles has been demonstrated to improve the functionality of peptides resulting in a versatile platform for biomedical applications. In this work, the development of carboxymethylchitosan/poly(amidoamine) (CMCht/PAMAM) dendrimer nanoparticles functionalized with YIGSR laminin receptor binding peptide for the active targeting and specific delivery of therapeutic agents into colorectal cancer cells is described. The successful functionalization is confirmed by several physico‐chemical characterization techniques. The selectivity of the YIGSR‐CMCht/PAMAM dendrimer nanoparticles is first validated in vitro using a micropatterned array of 67 kDa laminin receptor. Next, the specificity of YIGSR‐CMCht/PAMAM dendrimers nanoparticles toward laminin receptor is further confirmed both in 2D and 3D settings using HCT‐116 colorectal cancer cells and L929 fibroblasts in co‐culture. Finally, gemcitabine‐loaded YIGSR‐CMCht/PAMAM dendrimer nanoparticles induce a targeted mortality on HCT‐116 cancer cells in a co‐culture scenario. Overall, the study shows solid evidence that YIGSR laminin receptor binding peptide coupled to CMCht/PAMAM dendrimer nanoparticles may be employed as an anticancerous target for the specific and intracellular delivery of chemotherapeutic agents.