Improved therapeutic activity of HER2 Affibody-targeted cisplatin liposomes in HER2-expressing breast tumor models

ABSTRACT

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.

KEYWORDS:

• Affisome
• anti-HER2 Affibody
• breast cancer
• cisplatin
• stealth liposome

Acknowledgments

We would like to thank Azam Abbasi and Zahra Saberi for their excellent technical assistance.

Declaration of Interest

The financial support of the Biotechnology Research Center and Nanotechnology Research Center, Mashhad University of Medical Sciences (MUMS; grant nubmer: 901028) is gratefully acknowledged. This study was a part of HA’s Ph.D. dissertation. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.