Objectives: The purpose of this study was to investigate whether the conjugation of anti-HER2-Affibody to cisplatin PEGylated liposome can efficiently enhance the therapeutic effectiveness of the targeted liposome.

Methods: First, Affibody molecules were incubated with Mal-PEG₂₀₀₀-DSPE micelle to afford formation of a maleimide-mediated thioether coupling to the COOH-terminal cysteine of Affibody. Cisplatin-loaded liposomes composed of hydrogenated soy phosphatidylcholine/ cholesterol/mPEG₂₀₀₀-DSPE (56.5:38.5:5 molar ratio) (150 mM) were prepared and characterized by their physicochemical properties. Affibody-conjugated micelles were then transferred into preformed liposomes by means of post insertion. The cytotoxicity and cellular uptake of Affibody-targeted (affisome) and nontargeted liposomes were tested in HER2⁺ SK-BR-3, and the in vivo therapeutic activity was evaluated in TUBO breast cancer models.

Results: Anti-HER2 affisome demonstrated a higher amount of platinum intracellularly, and affected HER2⁺-SK-BR-3 cell death was at lower concentrations compared with its liposome counterparts. Further, cisplatin-affisome showed greater therapeutic efficiency than nontargeted liposome in HER2⁺-TUBO models. Equally promising, the affisome-treated mice did extend the survival of animals by several days and even left one tumor-free survivor.

Conclusions: Affibody-targeting endowed cisplatin liposomes with significantly enhanced, albeit modest, therapeutic activity in HER2-overexpressing tumor model; however, further values are yet to be determined to advance clinical translation of these targeted nanoparticulates.