Enhanced Anti-Tumoral Activity of Methotrexate-Human Serum Albumin Conjugated Nanoparticles by Targeting with Luteinizing Hormone-Releasing Hormone (LHRH) Peptide

International Journal of Molecular Sciences

Azade Taheri³  Rassoul Dinarvand³  Fatemeh Atyabi³  Fatemeh Ahadi³  Farank Salman Nouri³  Mohammad Hossein Ghahremani¹  Seyed Nasser Ostad¹  Atefeh Taheri Borougeni² 

[1] Nanotechnology Research Centre, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran 14174, Iran; E-Mails:;Department of Oral and Maxillofacial Pathology, Faculty of Dentistry, Tehran University of Medical Sciences, Tehran 14174, Iran; E-Mail:;Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran P. O. Box 14155-6451, Iran; E-Mails:

关键词: nanoparticles;    drug targeting;    conjugates;    anti-cancer;    human serum albumin;    LHRH;   

DOI  :  10.3390/ijms12074591

来源: mdpi

【 摘 要 】

Active targeting could increase the efficacy of anticancer drugs. Methotrexate-human serum albumin (MTX-HSA) conjugates, functionalized by luteinizing hormone-releasing hormone (LHRH) as targeting moieties, with the aim of specifically targeting the cancer cells, were prepared. Owing to the high expression of LHRH receptors in many cancer cells as compared to normal cells, LHRH was used as the targeting ligand in this study. LHRH was conjugated to MTX-HSA nanoparticles via a cross-linker. Three types of LHRH targeted nanoparticles with a mean particle size between 120–138 nm were prepared. The cytotoxicity of LHRH targeted and non-targeted nanoparticles were determined on the LHRH positive and negative cell lines. The internalization of the targeted and non-targeted nanoparticles in LHRH receptor positive and negative cells was investigated using flow cytometry analysis and fluorescence microscopy. The cytotoxicity of the LHRH targeted nanoparticles on the LHRH receptor positive cells were significantly more than non-targeted nanoparticles. LHRH targeted nanoparticles were also internalized by LHRH receptor positive cells significantly more than non-targeted nanoparticles. There were no significant differences between the uptake of targeted and non-targeted nanoparticles to the LHRH receptor negative cells. The active targeting procedure using LHRH targeted MTX-HSA nanoparticles could increase the anti-tumoral activity of MTX.

【 授权许可】

CC BY   
© 2011 by the authors; licensee MDPI, Basel, Switzerland.