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Trastuzumab decorated methotrexate-human serum albumin conjugated nanoparticles for targeted delivery to HER2 positive tumor cells.

Eur J Pharm Sci. 2012 Jul 5;

Authors: Taheri A, Dinarvand R, Atyabi F, Ghahremani MH, Ostad SN


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 123-346 nm according to the amount of TMAB molecules conjugated on their surfaces. The cytotoxicity of TMAB-MTX-HSA NPs on HER2 positive cells after 24 h 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 24 h. 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.

PMID: 22771547 [PubMed - as supplied by publisher]