Targeting, bio distributive and tumor growth inhibiting characterization of anti-HER2 affibody coupling to liposomal doxorubicin using BALB/c mice bearing TUBO tumors.

Abstract

Human epidermal growth factor receptor 2 (HER2) is overexpressed in 20-30% of breast cancer tumors. In the current investigation, we exploited such a feature and utilized an anti-HER2 affibody (ZHER2:477) in combination with a pegylated liposomal doxorubicin (PLD) for concurrent passive and active targeting of HER2 overexpressing TUBO tumor, using BALB/c mice. It was determined that the affibody coupled liposomes (affisomes) was capable of increasing doxorubicin (Dox) delivery to HER2+ cells (SK-BR-3 and TUBO cells), while transferring drug similarly as low as naïve PLD to HER2- MDA-MB-231 cells. This also resulted in selectively enhance cytotoxicity. The veracity of targeting was further assessed utilizing DiD lipophilic tracer model liposomes via competition assay. An approximated 10 ligand/liposome integration caused Dox delivery at 50% of maximal delivery capacity (Kd). Such integration did not alter Dox release in vitro, while it affected the serum clearance profile. Affibody integration to PLD increased drug concentration in tumor and led to significantly further augmentation of drug in liver and spleen compared to those of PLD. Overall, such differences led to prolonging the mice life spans as compared to PLD.

• Authors: Javad Akhtari, Seyed Mahdi Rezayat, Manouchehr Teymouri, Seyedeh Hoda Alavizadeh, Fatemeh Gheybi, Ali Badiee, Mahmoud Reza Jaafari
• Journal: International journal of pharmaceutics (Int J Pharm) Vol. 505 Issue 1-2 Pg. 89-95 (May 30 2016) ISSN: 1873-3476 [Electronic] Netherlands
• PMID: 27039149 (Publication Type: Comparative Study, Journal Article)
• Copyright: Copyright © 2016. Published by Elsevier B.V.

Chemical References

• Antibiotics, Antineoplastic
• Recombinant Fusion Proteins
• liposomal doxorubicin
• Polyethylene Glycols
• Doxorubicin
• ERBB2 protein, human
• Receptor, ErbB-2

Topics

• Adenocarcinoma (drug therapy, pathology)
• Animals
• Antibiotics, Antineoplastic (administration & dosage, pharmacokinetics, pharmacology)
• Breast Neoplasms (drug therapy, pathology)
• Doxorubicin (administration & dosage, analogs & derivatives, pharmacokinetics, pharmacology)
• Drug Delivery Systems
• Female
• Humans
• Mice
• Mice, Inbred BALB C
• Polyethylene Glycols (administration & dosage, chemistry, pharmacokinetics, pharmacology)
• Rats
• Receptor, ErbB-2 (metabolism)
• Recombinant Fusion Proteins (chemistry)