Seyedeh Hoda Alavizadeh1, Javad Akhtari2, Ali Badiee3, Shiva Golmohammadzadeh3, Mahmoud Reza Jaafari1. 1. a Biotechnology Research Center, Nanotechnology Research Center, School of Pharmacy , Mashhad University of Medical Sciences , Mashhad , Iran. 2. b Immunogenetics Research Center, Department of Physiology and Pharmacology, Faculty of Medicine , Mazandaran University of Medical Sciences , Sari , Iran. 3. c Nanotechnology Research Center, School of Pharmacy , Mashhad University of Medical Sciences , Mashhad , Iran.
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.
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.
Entities:
Keywords:
Affisome; anti-HER2 Affibody; breast cancer; cisplatin; stealth liposome
Authors: Vanessa Bellat; Richard Ting; Teresa L Southard; Linda Vahdat; Henrik Molina; Joseph Fernandez; Omer Aras; Tracy Stokol; Benedict Law Journal: Adv Funct Mater Date: 2018-09-14 Impact factor: 18.808
Authors: Muhammad Kashif Riaz; Muhammad Adil Riaz; Xue Zhang; Congcong Lin; Ka Hong Wong; Xiaoyu Chen; Ge Zhang; Aiping Lu; Zhijun Yang Journal: Int J Mol Sci Date: 2018-01-09 Impact factor: 5.923
Authors: Amin Mehrabian; Mohammad Mashreghi; Saba Dadpour; Ali Badiee; Leila Arabi; Seyedeh Hoda Alavizadeh; Seyedeh Alia Moosavian; Mahmoud Reza Jaafari Journal: Technol Cancer Res Treat Date: 2022 Jan-Dec