Development of a ZHER3‐Affibody‐Targeted Nano‐Vector for Gene Delivery to HER3‐Overexpressed Breast Cancer Cells

Abstract

Despite the initial successes of gene delivery applications, they faced on several intrinsic drawbacks including toxicity and immunogenicity. Therefore, alternative gene‐delivery systems derived from recombinant peptides have emerged and is rapidly developing. Human epidermal growth factor receptor‐3 (HER3) shows high activity in tumor resistance to anti‐human epidermal growth factor receptor 2 (HER2) therapies. In this study, an affibody molecule against HER3 is conjugated to a biomimetic peptide RALA (an amphipathic and cationic peptide enriched with arginine) and the ability of the fusion vector for targeting HER3 and afterward delivering specific genes in breast cancer cells is evaluated. The results demonstrate that the biopolymeric platform, which contains an affibody‐conjugated RALA peptide, can effectively condense DNA into nanoparticles and target the overexpressed HER3 receptors in breast cancer cells and transfer specific genes. The use of such a recombinant biopolymer may pave the way for the development of sensitive and effective diagnostic and treatment tool for breast cancer.

Enhanced delivery of protein therapeutics with a diphtheria toxin-like platform that evades pre-existing neutralizing immunity

“…3d ). The solid tumour receptors HER3 28 and integrin ανβ6 29 were also similarly targeted, on pancreatic cancer cells ( Fig. 3e ).…”

“…Recently, groups including ours, have demonstrated the potential of DTT to deliver other protein cargo of interest into cells, expanding the therapeutic utility of DT [30][31][32][33] . To evaluate the ability of CTT to serve as a general translocase of diverse protein cargo of therapeutic interest, we designed DT and CT-based translocase constructs flanked by flexible linkers that were retargeted with either a HER3-targeting affibody 28 or a TEM8-targeting scFv 34 (Fig. 4a, b).…”