Targeted Delivery of Anti-HER2 Affibody Conjugated Sterically Stabilized Cisplatin Liposome in HER2Receptor-Expressing Breast Cancer Models

HER2-targeted nanoparticle bioconjugates have shown to be capable of triggering receptormediatedendocytosis by combining the tumor-specificity of affibody molecules with drugdelivery features of a sophisticated macromolecular carrier. The purpose of this study was toinvestigate if the conjugation of Anti-HER2-affibody to cisplatin PEGylated liposomes canefficiently target cisplatin delivery to HER2+ breast tumor models and enhance thetherapeutic effectiveness of targeted liposomes. Affibody molecules were incubated with Mal-PEG2000-DSPE micelle to afford formation of a stable maleimide-mediated thioethercoupling to the COOH-terminal cysteine of the affibody. The covalent linkage was determinedby SDS-PAGE. Cisplatin loaded liposomes composed of HSPC/ cholesterol/ mPEG2000-DSPE (56.5:38.5:5 molar ratio) (150 mM) were prepared by ethanol injection and thephysicochemical properties of nanoparticles were characterized. Transfer of affibody intopreformed liposomes was carried out by post-insertion. The in vitro cytotoxicity and cellularuptake, and in vivo therapeutic activity of affibody-targeted (affisome) and non-targetedliposomes were tested in HER2+ SK-BR-3 and TUBO breast cancer models, respectively.Anti-HER2 affisome demonstrated a higher amount of platinum intracellularly, and affectedHER2+ SK-BR-3 cell death was at lower concentrations compared to its liposomecounterpart. Further, cisplatin-affisome showed greater therapeutic efficiency than nontargetedliposome in HER2+ TUBO models. Equally promising, the affisome-treated mice didextend the survival of animals by several days and even left one tumor-free survivor. Affibodytargetingendowed cisplatin liposome with significantly enhanced, albeit modest, therapeuticactivity in HER2-overexpressing tumor models, however, further values are yet to bedetermined to advance clinical translation of affibody-targeted liposome nanoparticles.

کلیدواژه ها:

Affisome ، Anti-HER2 Affibody ، Breast Cancer ، Cisplatin ، Stealth liposome