RETRACTED: siRNA-loaded poly(histidine-arginine)6-modified chitosan nanoparticle with enhanced cellpenetrating and endosomal escape capacities for suppressing breast tumor metastasis (Retracted article. See vol. 18, pg. 1897, 2023)

An ideal carrier that delivers small interfering RNA (siRNA) should be designed based on two criteria: cellular-mediated internalization and endosomal escape. Poly(histidinearginine) (6)(H6R6) peptide was introduced into chitosan (CS) to create a new CS derivative for siRNA delivery, 6-polyarginine (R6) as cell-penetrating peptides facilitated nanoparticle cellular internalization has been proved in our previous research, and 6-polyhistidine (H6) mediated the nanoparticle endosome escape resulted in the siRNA rapid releasing into tumor cytoplasm. H6R6-modified CS nanoparticles showed higher transfection efficiency and better endosomal escape capacity compared to ungroomed CS nanoparticle in vitro. Noticeably, H6R6-modified CS nanoparticles effectively inhibited tumor cell growth and metastases in vivo and significantly improved survival ratio. Therefore, we concluded that H6R6-modified CS copolymer can act as an ideal carrier for siRNA delivery and as a promising candidate in breast cancer therapy.