Specific targeting of human epidermal growth factor receptor 2 (HER2) overexpressing breast cancer cells by polyethylene glycol-grafted polyethyleneimine modified with anti-HER2 single-domain antibody

Abstract

Polyethyleneimine is one of the most efficient non-viral gene delivery agents. However, some limitations such as non-specific cell binding, interactions with blood components, and relatively high cytotoxicity restrict its in vivo applications. In order to improve the properties of this molecule as a gene transfection vector, in this study, we developed a nano-carrier system based on polyethyleneimine derivatives synthesized by grafting bi-functional polyethylene glycol molecules (MAL-PEG 3500-NHS) to 25 kDa branched polyethyleneimine polymer at three different molar ratios of 10, 20, and 30 (polyethylene glycol:polyethyleneimine). Variable domain of heavy-chain antibody against human epidermal growth factor receptor 2 as targeting agent was conjugated to polyethylene glycol-polyethyleneimine copolymer. In order to find the most effective resultant conjugate, the effect of these modifications on physicochemical properties, cytotoxicity, cellular uptake, and gene transfection efficiency of polyethyleneimine polymer was evaluated. According to the findings of this study and compared to unconjugated polyethyleneimine, PEGylated polyethyleneimine copolymers exhibit lower in vitro cytotoxicity. Polyethylene glycol-polyethyleneimine copolymer conjugated at a molar ratio of 10:1 (polyethylene glycol:polyethyleneimine) demonstrated a low cytotoxicity effect and desirable physicochemical properties. Anti-human epidermal growth factor

Anti–HER2 single domain antibody-conjugated dendrimers for targeted delivery of truncated-Bid transgene to breast cancer cells

“…26 These data were furthermore confirmed in another study, where we showed that this killer gene was also able to kill the HER2-positive cancer cells, using anti-HER2 VHH-conjugated PEG-PEI polyplexes. 29…”

“…For transcriptional targeting, we used MUC1 gene promoter because its tumor specificity and elevated protein expression had been confirmed in breast cancer. 1,26,28,29 In this study, anti-HER2 targeted dendrimers were used as compacting agents of transcriptionally targeted tBid killer gene construct, and their selective delivery into HER2-expressing cell lines was thoroughly evaluated. This study provides a significant proof of concept in combining VHH-based targeting with transcriptional targeting as a safe and effective alternative to deliver transgenes to specific cells in vitro.…”

Ultra-small NIR-Responsive Nanotheranostic Agent for Targeted Photothermal Ablation Induced Damage-Associated Molecular Patterns (DAMPs) from Post-PTT of Tumor Cells Activate Immunogenic Cell Death

“…It is hydrophobic, economical and is highly biocompatible. It is an efficient DNA condensing agent as it exhibits a high positive charge density which further leads to a high electrostatic interaction with the anionic DNA 25 . PEI adds quality to the NPs by being a better stabilizer for two major reasons, one being a branched architecture which allows the wrapping or surrounding the core in a highly efficient way and other factor is that it contains all types of amino groups- primary, secondary, tertiary groups and thus is vital anchoring groups especially on sulfide surfaces 26 .…”