title: Functionalized nanoscale β-1,3-glucan to improve Her2+ breast cancer therapy: In vitro and in vivo study.
abstract: We fabricated a targeted delivery system for doxorubicin (Dox) using β-1,3-glucan (Glu) as a carrier and decorated by trastuzumab antibody having the status of targeting agent against Her2+ breast tumors. Glu-Dox conjugates were also functionalized with polyethylenimine (PEI) intended for increasing specific cellular uptake of prepared nanoparticles. The self-assembled nanoparticles were prepared through conjugation of Dox- [Glu-Dox-] using succinic anhydride (Sa) in place of a linker. Nanoparticles had spherical morphology with positive zeta potential. In-vitro cell viability assay on two breast cancer cell lines demonstrated acceptable toxicity against tested cell lines. Confocal microscopic images demonstrated the remarkable cytoplasmic uptake of the nanoparticles in Her2-overexpressing 4T1 cells. A controlled release of Dox from Glu-Dox nanoparticles was investigated. In-vivo studies were performed on female Balb/C mice. The volume of the induced tumors was calculated following intravenous administration of nanoparticles. The tumor volume diminished efficiently and more rapidly after administration of nanoparticles containing Dox. Based on survival results, the formulation of Dox targeted nanoparticles appeared very promising for the treatment of tumors. It could be concluded that Glu-Dox targeted nanoparticles have potential advantages for delivering anticancer drugs to the target tissue.
authors.affiliation: Department of Medical Mycology, Faculty of Medicine, Tarbiat Modares University, Tehran, Iran.
authors.forename: Zahra
authors.initials: Z
authors.lastname: Nasrollahi
authors.affiliation: Department of Medical Mycology, Faculty of Medicine, Tarbiat Modares University, Tehran, Iran. Electronic address: sh.mohammadi@modares.ac.ir.
authors.forename: Shahla Roudbar
authors.initials: SR
authors.lastname: Mohammadi
authors.affiliation: Nanotechnology Research Centre, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Esmail
authors.initials: E
authors.lastname: Mollarazi
authors.affiliation: Department of Medical Mycology, Faculty of Medicine, Tarbiat Modares University, Tehran, Iran.
authors.forename: Mohammad Hossein
authors.initials: MH
authors.lastname: Yadegari
authors.affiliation: Department of Immunology Faculty of Medicine, Tarbiat Modares University, Tehran, Iran.
authors.forename: Zuhair Mohammad
authors.initials: ZM
authors.lastname: Hassan
authors.affiliation: Nanotechnology Research Centre, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Talaei
authors.affiliation: Nanotechnology Research Centre, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Rassoul
authors.initials: R
authors.lastname: Dinarvand
authors.affiliation: Department of Pathology Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Hassan
authors.initials: H
authors.lastname: Akbari
authors.affiliation: Nanotechnology Research Centre, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: atyabifa@tums.ac.ir.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Atyabi
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000008:administration & dosage / Q000737:chemistry; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry*; D065546:Drug Liberation; D005260:Female; D061986:MCF-7 Cells; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry*; D011094:Polyethyleneimine / Q000737:chemistry*; D018719:Erb-b2 Receptor Tyrosine Kinases; D013386:Succinates / Q000737:chemistry*; D000068878:Trastuzumab / Q000008:administration & dosage / Q000737:chemistry; D047368:Tumor Burden / Q000187:drug effects; D047071:beta-Glucans / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D004317:Doxorubicin; D004337:Drug Carriers; D011094:Polyethyleneimine; D018719:Erb-b2 Receptor Tyrosine Kinases; D013386:Succinates; D000068878:Trastuzumab; D047071:beta-Glucans; C033363:beta-1,3-glucan
keywords: Active targeting; Doxorubicin; Drug delivery; Trastuzumab; β-1,3-glucan