Surfactant like peptides for targeted gene delivery to cancer cells

Surfactant like peptides (SLPs) are a class of amphiphilic peptides widely used for drug delivery and tissue engineering. However, there are very few reports on their application for gene delivery. The current study was aimed at development of two new SLPs, named (IA)4K and (IG)4K, for selective delivery of antisense oligodeoxynucleotides (ODNs) and small interfering RNA (siRNA) to cancer cells. The pep-tides were synthesized by Fmoc solid phase synthesis. Their complexation with nucleic acids was studied by gel electrophoresis and DLS. The transfection efficiency of the peptides was assessed in HCT 116 colorectal cancer cells and human dermal fibroblasts (HDFs) using high content microscopy. The cyto-toxicity of the peptides was assessed by standard MTT test. The interaction of the peptides with model membranes was studied using CD spectroscopy. Both SLPs delivered siRNA and ODNs to HCT 116 colo-rectal cancer cells with high transfection efficiency which was comparable to the commercial lipid-based transfection reagents, but with higher selectivity for HCT 116 compared to HDFs. Moreover, both peptides exhibited very low cytotoxicity even at high concentrations and long exposure time. The current study provides more insights into the structural features of SLPs required for nucleic acid complexation and delivery and can therefore serve as a guide for the rational design of new SLPs for selective gene delivery to cancer cells to minimize the adverse effects in healthy tissues.(c) 2023 Elsevier Inc. All rights reserved.

Automated summary

In this study, two new surfactant-like peptides (SLPs), named (IA)4K and (IG)4K, were developed for selective delivery of antisense oligodeoxynucleotides (ODNs) and small interfering RNA (siRNA) to cancer cells. The interaction of the peptides with nucleic acids, their transfection efficiency, and cytotoxicity were investigated. Both SLPs showed high transfection efficiency and selectivity for cancer cells, and exhibited low cytotoxicity. This study provides insights into the structural features required for nucleic acid complexation and delivery, and serves as a guide for the design of new SLPs for selective gene delivery to minimize adverse effects in healthy tissues.