title: Trastuzumab decorated methotrexate-human serum albumin conjugated nanoparticles for targeted delivery to HER2 positive tumor cells.
abstract: Targeted drug delivery systems could reduce the systemic toxicity of anticancer drugs following cancer chemotherapy. In this study we developed methotrexate-human serum albumin conjugated nanoparticles (MTX-HSA NPs) which were surface decorated using trastuzumab (TMAB) molecules. The size of TMAB-MTX-HSA NPs was between 123 and 346 nm according to the amount of TMAB molecules conjugated on their surfaces. The cytotoxicity of TMAB-MTX-HSA NPs on HER2 positive cells after 24h was significantly higher than that for non-targeted MTX-HSA NPs and also free MTX. However when the number of attached TMAB molecules was very high, the cytotoxicity of TMAB-MTX-HSA NPs was similar to the cytotoxicity of non-targeted MTX-HSA NPs approximately. There were no significant differences between cytotoxicity of TMAB-MTX-HSA NPs and MTX-HSA NPs for HER2 negative cells after 24h. The results of flow cytometry analysis showed that the binding activity of TMAB molecules remained approximately unchanged after conjugation, if the number of the attached TMAB molecules on the surface of MTX-HSA NPs was not very high. Moreover, TMAB-MTX-HSA NPs showed higher uptake to HER2 positive cells compared to non-targeted MTX-HSA NPs when the optimized amount of TMAB was conjugated on the surface of NPs. In conclusion, conjugation of TMAB molecules on the MTX conjugated HSA nanoparticles is an appropriate method for active tumor targeting of MTX.
authors: Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran 1417614411, Iran.
authors: Azade
authors: A
authors: Taheri
authors: Rassoul
authors: R
authors: Dinarvand
authors: Fatemeh
authors: F
authors: Atyabi
authors: Mohammad Hossein
authors: MH
authors: Ghahremani
authors: Seyed Nasser
authors: SN
authors: Ostad
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage* / Q000737:chemistry; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D008727:Methotrexate / Q000008:administration & dosage* / Q000737:chemistry; D046529:Microscopy, Electron, Transmission; D058726:Nanoconjugates / Q000008:administration & dosage* / Q000737:chemistry / Q000648:ultrastructure; D018719:Erb-b2 Receptor Tyrosine Kinases; D012709:Serum Albumin / Q000008:administration & dosage* / Q000737:chemistry; D000068878:Trastuzumab
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D008727:Methotrexate; D058726:Nanoconjugates; D018719:Erb-b2 Receptor Tyrosine Kinases; D012709:Serum Albumin; D000068878:Trastuzumab; C040811:methotrexate-serum albumin; C508053:ERBB2 protein, human