title: 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.affiliation: Immunogenetics Research Center, Department of Physiology and Pharmacology, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari 48471-91971, Iran.
authors.forename: Javad
authors.initials: J
authors.lastname: Akhtari
authors.affiliation: Department of Medical Nanotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran 14177-55469, Iran; Department of Toxicology and Pharmacology, School of Pharmacy, Pharmaceutical Sciences Branch, Islamic Azad University (IAUPS), Tehran, Iran.
authors.forename: Seyed Mahdi
authors.initials: SM
authors.lastname: Rezayat
authors.affiliation: Biotechnology Research Center, Nanotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad 91775-1365, Iran.
authors.forename: Manouchehr
authors.initials: M
authors.lastname: Teymouri
authors.affiliation: Biotechnology Research Center, Nanotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad 91775-1365, Iran.
authors.forename: Seyedeh Hoda
authors.initials: SH
authors.lastname: Alavizadeh
authors.affiliation: Department of Medical Nanotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran 14177-55469, Iran.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Gheybi
authors.affiliation: Nanotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad 91775-1365, Iran.
authors.forename: Ali
authors.initials: A
authors.lastname: Badiee
authors.affiliation: Nanotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad 91775-1365, Iran. Electronic address: jafarimr@mums.ac.ir.
authors.forename: Mahmoud Reza
authors.initials: MR
authors.lastname: Jaafari
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004317:Doxorubicin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D016503:Drug Delivery Systems; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D051381:Rats; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000737:chemistry
chemical_list: D000903:Antibiotics, Antineoplastic; D004317:Doxorubicin; D011092:Polyethylene Glycols; D018719:Erb-b2 Receptor Tyrosine Kinases; D011993:Recombinant Fusion Proteins; C506643:liposomal doxorubicin; C508053:ERBB2 protein, human
keywords: (PubChem CID: 3776); (PubChem CID: 443939); (PubChem CID: 5997); (PubChem CID: 6049); (PubChem CID: 6212); (PubChem CID: 9285); Affibody; Affisome; Ammonium sulfate (PubChem CID: 6097028); Doxorubicin; HER2; Pegylated liposome