Nanoparticle delivery of TFOs is a novel targeted therapy for HER2 amplified breast cancer

Abstract

Purpose The human EGFR2 (HER2) signaling pathway is one of the most actively studied targets in cancer transformation research. Ttriplex-forming oligonucleotides (TFOs) activate DNA damage and induce apoptosis. We aim to encapsulate TFO-HER2 with nano-particle ZW-128 to suppress breast cell growth in vitro and in vivo. Experimental design We designed a set of TFO fragments targeting HER2 and verified their effectiveness. We encapsulated TFO-HER2 in ZW-128 to form nano-drug TFO@ZW-128. Cell counting kit 8, flow cytometry, and western blotting were used to evaluate the effect of TFO@ZW-128 on cell proliferation and the expressions of related proteins. The ant-itumor effect of TFO@ZW-128 was evaluated in vivo using nude mice breast cancer model. Results TFO@ZW-128 had efficient cellular uptake in amplified HER2 breast cancer cells. TFO@ZW-128 showed an 80-fold increase in TFO utilization compared with TFO-HER2 in the nude mouse breast cancer model. Meanwhile, TFO@ZW-128 dramatically inhibited the growth of HER2-overexpressing tumors compared with TFO-HER2 (P < 0.05). Furthermore, TFO@ZW-128-induced cell apoptosis was in a p53-independent manner. Conclusions In this study, we designed nano-drug TFO@ZW-128, which has proven effective and non-toxic in targeted therapy for ectopic HER2-expressing tumors.

Recent Advancements in Development and Therapeutic Applications of Genome-Targeting Triplex-Forming Oligonucleotides and Peptide Nucleic Acids

“…Recently, the therapeutic potential of TFOs against the HER2-gene-amplified breast cancer was reported [26,76]. Rogers's group demonstrated the selective apoptosis induction of the HER2-amplified breast cancer cells by targeting amplified HER2-gene loci with TFOs.…”